Medical Biochemistry-Exam 3 (Everything) – Flashcards

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question
In which human organ is myoglobin (Mb) most impt?
answer
heart b/c rapid O2 supply needed
question
Explain causes and importance of right shift in Hb/O2 binding curve
answer

right shift caused by:

 

decreased pH (increased [H+])

 

increased [CO2]

 

increased [2,3-BPG]

 

increased temperature

 

all factors lead to increased O2 unloading which means that a higher percentage of O2 is delivered to tissues

question
In Hb, how does binding of first oxygen molecule affect binding of next ones?
answer

Deoxy Hb is usually in taut (T) form where heme groups restricted and hard for O2 to bind

 

When O2 binds to 1st heme group, the Fe of that heme will shift and pull attached his along.

 

Movement breaks salt bridges pushing Hb into relaxed (R) state and allow more O2 binding sites to become available

 

 

question
What is Bohr effect?
answer

A right shift when pH decreases (increase in H+ conc.)

 

O2 release from Hb will increase when pH is lowered or [CO2] is high

 

Hb has decreased O2 affinity

 

Raising pH or decreasing [CO2]-shift curve to left

question
Physiological importance of cooperativity in Hb function
answer
Hb has 4 subunits where binding of O2 at one heme group increases the affinity for O2 of the other heme groups in the same molecule
question
Compare behavior of Mb and Hb with respect to O2, CO2, and H+
answer

Mb has a greater affinity at lower [O2] than Hb

 

Hb can transport more molecules of O2 b/c of cooperative effect of multiple binding sites

 

Hb can't readily bind 1st O2, but once it does has higher affinity for O2 at other sites

;

Hb-sigmoidal curve

;

Mb-hyperbolic

;

Hb responds more readily to small changes in partial pressures of O2

;

Mb saturated quicker than Hb at low partial pressure of O2 (doesn't have much flexibility)

question
How does protein (globin) portion of Mb or Hb affect reactivity of heme?
answer

weaken strength of heme-O2 interaction. Heme binds O2 so stronglyit can convert it to a superoxide anion, which can be an unwanted oxidizing agent

 

prevents interaction of oxy-heme groups with other oxy-heme groups

question
How and where does 2,3-BPG interact with Hb?
answer

2,3-BPG binds to deoxy Hb-makes it more stable and resistant to oxygenation after O2 delivery

 

negative charge allows BPG to bind to a site between two alpha chains

 

causes right shift in O2-dissociation curve (lower O2 release)

question
Where does 2,3-BPG come from?
answer
product of glycolytic pathway
question
How does fetal Hb (HbF) differ from HbA?
answer

Fetal Hb has two gamma chains instead of beta chains.

 

2,3-BPG can't bind to fetal Hb and it has greater affinity fo O2 and takes O2 from maternal Hb

;

HbF is left shifted on O2-dissociation curve compared to maternal Hb

;

;

question
What does Hill Eqn describe?
answer
importance of cooperativity
question
How does NO interact w/ Hb and what is physiological significance of that interaction?
answer

Hb binds NO at heme Fe and cys residues in globin chain.

;

NO relaxant for vascular smooth muscle

;

Hb can pick up NO, stiffen vascular tissues, and increase BP

;

NO is strong vasodilator so Hb can be used to mediate vascular tone

question
What is difference btwn HbS and HbA?
answer
HbA has normal beta chain while HbS has sickly cell hemoglobin. 6th AA for normal beta globin would be a glutamic residue but in HbS that Glu is replaced with a Val. Val is uncharged and allows hydrophobic pockets. The chains bind together and crystallize
question
Physiochemical/Pathological Basis for All Clinical Manifestations of Sickle Cell Disease
answer

crystallization and stiffening of Hbs causes them to adhere to the endothelium and often obstruct small vessels (capillaries) or cause hemolysis

;

hemolysis can cause anemia and hyperbilirubinemia, causing pallor and jaundice

;

Complete vasocclusion can cause ishemia or infarction resulting in organ damage

;

Stroke, infection and excrutiating pain can result

question
How is Sickle Cell Disease Inherited?
answer
recessive disorder. Only homozygous HbS cause the disease to become expressed.
question
What is an enzyme?
answer

a protein catalyst for specific biochem rxns.

;

It will not undergo chem rxnitself and can be reused for other rxns

question

What does enzyme effect and not effect in rxn?

;

;

answer

Enzymes reduce activation energy.

;

Keq and delta G are not affected by enzymes.

question
Name and describe 2 models used to describe enzyme specificity and/or catalytic activity
answer

lock and key model

;

describes an enzyme active sites (lock) being specific for binding substrate (key)

describe specificity

;

induced fit model

;

active site will conform to fit substrate

describes specificity and catalytic activity

question
What is prosthetic group?
answer

non-protein organic molecule that is tightly bound to enzyme active site

;

ex-heme, biotin, or flavin

;

holoenzyme-prosthetic group attached

;

apoenzyme-prosthetic group NOT attached

question
Name 6 Classes of Enzymes
answer

oxidoreductases-catalyze RED/OX reactions

Ex-H+ donor to substrate


transferases-transfer group from one molecule to another

Ex-phosphoylases


hydrolases-hydrolytic cleavage of bond

Ex-peptide bond cleavage


lyases-cleave bonds w/o water to leave double bond or addition of other groups to double bond

Ex-decarboxylase


isomerases-change geometry of molecule

Ex-cis-trans isomerase


ligases-join 2 molecules together though hydrolysis of high energy bond

Ex-carboxylase

question
What is Michaelis-Menton Eqn and what do terms mean?
answer

V = Vmax[S]/(Km+[S])

;

V - velocity of rxn

Vmax - max rxn velocity

[S] - substrate concentration

Km - constant value for a specific substrate

;

question
In a Michaelis-Menton plot, where is Vmax and how do you find Km?
answer

Vmax - when [S] is very high

;

Km - [S] when V = 1/2(Vmax)

question
A Lineweaver-Burk plot is also called a ---------
answer
Double-reciprocal plot
question
What is plotted on Lineweaker-Burk plot and what are the x- and y-intercepts of the plot?
answer

The LB graph plots the inverse of the Michaelis-Menten plot, which is 1/V on the y-axis and 1/[S] on the x-axis

 

x-intercept - 1/Km

 

y-intercept - 1/Vmax

question
What are advantages of the Eadie-Hofstee plot?
answer
The E-H plot gives more evenly spaced data points than the  L-B plot.
question
What characteristics distinguish a competitive inhibitor from the other types of inhibitors?
answer

bind directly to the active site and can be overcome by increased [substrate].

 

Other inhibitors bind to other sites on enzyme

question
On the Lineweaver-Burk plots are the vertical or horizontal intercepts the same or different for competitively inhibited rxns?
answer

same y-intercept

 

different x-intercepts

question
On the Lineweaver-Burk plots are the vertical or horizontal intercepts the same or different for non-competitively inhibited rxns?
answer

different y-intercepts

 

same x-intercepts

question
On the Lineweaver-Burk plots are the vertical or horizontal intercepts the same or different for uncompetitively inhibited rxns?
answer

different y-intercepts

 

different x-intercepts

question
What does inhibitor react with for competitive inhibition?
answer
active site of the enzyme
question
What does inhibitor react with for non-competitive inhibition?
answer
react with enzyme to reduce its effectiveness to bind w/ substrate
question
What does inhibitor react with for uncompetitive inhibition?
answer

bind with ES complex.

 

irreversible inhibitors.

question
Sigmoid V versus [S] plot and curved Lineweaver-Burk plots indicate
answer
allostery and positive cooperativity of the enzyme (n = 2)
question
What factors determine the amount of enzyme activity in serum?
answer

amount of tissue producing enzyme

 

rate of enzyme released

 

rate of enzyme inactivation/elimination from plasma

question
Define: Standard International Unit (SIU)
answer
1 standard international unit of enzyme activity converts 1 μM of substrate/minute
question
2 most commonly measured serum aminotransferases and describe rxns they catalyze
answer

Aspartate aminotransferase (AST) - catalyzes exhange of amino group between alpha amino acids (aspartate) and alpha keto acids

 

Alanine aminotransferase (ALT) - catalyzes exchange of amino group between alpha amino acids (alanine) and alpha keto acids

question
In which pathological states are the two most commonly measured serum aminotransferases elevated?
answer

AST - liver damage and myocardial cells,hemolysed blood

 

ALT - liver damage

question
Reaction catalyzed by γ-glutamyltranspeptidase and how it is used diagnostically?
answer

Glutathione + amino acids → γ-glutamyl-amino acid + cys-gly

 

γ-glutamyltranspeptidase found in kidney, intestine, liver, and fetal tissue

 

GGT levels are elevated and very sensitive in liver damage

 

question
2 commonly measured phosphatases and how are they used diagnostically?
answer

Alkaline phosphatase (ALP)

 

Hydrolyzez phosphate groups from organic monophosphate at pH~9

Found in liver, bone, intestine, and placental tissue

Elevation of ALP means damage to liver and bone tissue

Elevated in gowing children, bone fractures, and pregnant women

 

Acid Phosphatase

 

hydrolyzes phosphate groups from organic monophosphates at pH~5

 

found in prostate, platelets, and erythrocytes

Elevation found in metastatic prostate cancer and hemolysed blood samples

 

 

question
Diagnostic utility of LDH
answer
Used to detect MI and hemolysis
question
"flipped" LDH
answer

Most common form is LDH2 (HHHM)

 

After MI or hemolysis, LDH1 (HHHH) predominates causing a "flipped" LDH b/c LDH1>LDH2

question
What reaction does LDH catalyze?
answer

Lactate + NAD → pyruvate + NADH + H

 

interconversion of pyruvate and lactate

question

Another name for alpha hydroxybutyrate dehydrogenase (HBD)?

 

 

answer
LDH1
question
What does elevated serum HBD mean?
answer
damage to myocardial cells due to recent MI
question
Reaction catalyzed by CK (CPK)
answer
creatine phosphate + ADP → Creatine + ATP
question
Diagnostic meaning of elevated serum CK
answer

has 2 subunits, M and B

 

MB-MI or brief ischemia

 

MM-vigorous exercise, injection, convulsions

 

BB-neural tissue damage

question
Diagnostic significance of elevated serum amylase
answer

pancreatitis

 

morphine

question
Reaction catalyzed by serum amylase
answer

starch + H2O → maltose, maltotriose & limit dextrins

 

digest starch

question
Elevated serum lipase means
answer

pancreatic pathology

 

morphine

question
Reaction catalyzed by serum lipase
answer

trigylceride + H2O → fatty acids + glycerol

 

fat digestion

question
What are troponins and how are they used in diagnosis?
answer

proteins that function in the contractile apparatus of the muscle

 

Cardiac troponin I is increased in plasma 3-6 hours after MI

question
Serum Enzyme Levels in crush injury
answer

mildly elevated alkaline phosphatase (healing bone)

 

elevated creatine kinase MM (skeletal muscle)

question
Serum Enzyme Levels in vigorous exercise
answer
elevated creatine kinase MM (skeletal muscle)
question
Serum Enzyme levels in morphine injection
answer
elevation of serum amylase and lipase
question
Serum Enzyme Levels in pregnancy
answer

mildly elevated alkaline phosphatase (bone growth)

 

elevated GGT

question
Four Categories of Cell Adhesion Molecules
answer

integrins

 

immunoglobulin superfamily

 

cadherins

 

selectins

question
Which of the CAM categories would be actively involved in transmitting signals from the inside to the outisde of the cells and vice versa?
answer
integrins
question
What CAM category is involved in adherens junction between cell?
answer
cadherins
question
Abbreviations for 3 types of adhesion molecules of Ig suberfamily and tell their origins
answer

NCAM - neural cell adhesion molecule

 

PECAM - platelet-endothelial cell adhesion molecule

 

VCAM - vascular cell adhesion molecule

 

Named for their similarity in structure to the Igs

question
4 Diseases in which CAMS are involved
answer

Rheumatoid arthritis - overexpression of VCAMs

 

Psoriasis - form of an integrin

 

Pemphigus vulgaris - autoantibodies interacting with desmoglein

 

von Willebrand disease - expression of P-selectin

question
Describe alpha-helix
answer
tightly coiled, stabilized by H bonding btwn imido groups and oxygen of carbony groups, many helices (3.6 AA/turn)
question
Beta sheet
answer

regions of same chain or neighboring chains bond to each other w/ H bonds, the H bonds are perependicular to the long axis of the chain

 

most stable conformation - antiparallel sheets (one side N→C other side C→N

question
Beta turns
answer

H bonding of AA 3 sequences apart in same chain

 

results in U turn bend of chain

question
What AA usually phosphoylated in proteins?
answer

ser

 

thr

 

tyr

question
Commonly occurring modification of AA found in some proteins
answer

acetylation of N terminus

 

carboxylation - add COOH

 

hydroylation - add OH

 

glycosylation - add glucose

 

phosphorylation - add phosphate group

 

disulfide linkages

question
Primary Structure
answer
AA sequence
question
Secondary Structure
answer

alpha helix

 

beta-pleated sheets

 

beta-turns

 

random coiling

 

results from free roation of bonds besides peptide bonds

question
Tertiary Structure
answer

secondary structures fold on each other

 

hydrophobic - inside

hydrophilic - outside

question
Quarternary Structure
answer
multiple polypeptide chains interact by noncovalent bonds to form single structure
question
General Solubility Prop. of Proteins
answer

fibrous and insoluble

 

globular and soluble

 

firbrous and soluble

question
Functions of Proteins
answer

structural roles

 

enzymes

 

role in contractile structures

 

transport (Hb)

 

hormones

 

receptors

 

Abs

question
What are proteins and peptides made of?
answer

peptides - moderate chain length polymers of amino acids joined by peptide bonds

 

proteins - polymeric compounds composed of AA joined by peptide bonds

question
What is unique about peptide bond?
answer
it is rigid b/c tautomerism
question
In ABO blood group, where is difference in oligosaccharide located and how sugars different?
answer

due to presence or absence of N-acetyl-galactosamine or galactose linked to penultimate galactose by C1-C3 linkage

 

1 sugar difference

question
Glycosaminoglycans and 2 Ex
answer

unbranched polysacc w/ repeating disacc - one is AA, other is uronic acid

 

Ex - hyaluronic acid and heparin

question
3 Impt Disacc and which alpha or beta linked?
answer

maltose - alpha linked

 

sucrose - alpha linked

 

lactose - beta linked

question
3 Most Impt polysacc and what are linkages? Why is linkage impt?
answer

starch - alpha linked (spiral)

 

glycogen - 2 types - alpha C1-C4 (linear)

                                 alpha C1-C6 (branched)

 

cellulose - beta linked (linear)

 

alpha and beta linkage affects the shape of the compound and humans can't digest cellulose b/c beta linkages

question
What is glycoside?
answer

anomeric -OH group of sugar reacts w/ another -OH compound

 

 

question
aglycone
answer
compound that attaches to anomeric C of sugar
question
Name and describe 2 commonly found mod. of sugars
answer

amino sugar - -OH group replaced by amino group

Ex - glucosamine, galactosamine

 

deoxy sugar - 1 OH group replaced by H

Ex - 2-deoxyribose

question
2 conformation of 6-membered rings
answer
boat and chair
question
What is mutarotation and where does it take place?
answer

configuration changes in molecule by ring opening and closing

 

occurs at anomeric C

question
Pyran and furan are named after which sugar structures and how many Cs are in each?
answer

pyranose - 6 C ring

 

furanose - 5 C ring

question
Most Impt Monosacc and Polysacc made up of this monosacc
answer

glucose - most impt monosacc

 

Polysacc made up of glucose - starch

                                             cellulose

                                             glycogen

question
What are aldoses?
answer
monosaccharides w/ aldehyde group
question
What are ketoses?
answer
monosaccharides w/ ketone group
question
What are carbohydrates?
answer
polyhydroxy aldehydes or ketones or compounts that can by hydrolyzed to these
question
4 Types of Compounds of which AAs are precursors
answer

hormones

 

nucleotides

 

neurotransmitters

 

AAs

question
Essential AA
answer

Pvt. Tim Hall

 

Phe

Val

Thr

 

Trp

Ile

Met

 

His

Arg

Leu

Lys

question
What is nucleotide not found in DNA or RNA that has role in energy metabolism?
answer
NAD+
question
Patient given adenosine during cardiac arrythmia. EKG during adenosine txt show AV block. If adenosine discontinuation does work, what will?
answer
theophylline
question
Nucleoside more useful that nucleotide as a drug b/c
answer
nucleoside does not have phosphate group, which restricts movement inside body
question
Biochemical mechanism that enables coffee-drinking college student to stay awake
answer

caffeine is competitive antagonist of adenosine receptor.

 

Blocks depressant action of adenosine-R and is therefore a stimulant

question
What is the modification of a normal base found in mRNA?
answer
methylated guanine
question
What is mod of a normal DNA base that affects gene expression?
answer
methylated cytosine
question
What happens when DNA exposed to 94 degrees C temperature during PCR?
answer
denaturation and 2 strands separate
question
What does it mean that DNA strands are "antiparallel"?
answer

strands run in opposite directions

 

one strand goes 3'5'

 

other strand goes 5'3'

question

Number of H bonds between A and T

 

Number of H bonds between G and C

answer

A-T : 2 bonds

 

G-C: 3 bonds

question
Difference between nucleotide and nucleic acid
answer

nucleotide - 1 molecule w/ phosphate group, base, and sugar

 

nucleic acid-several nucleotides connected w/ phosphodiester bonds

question
What 4 bases in DNA
answer

adenine

 

thymine

 

cystosine

 

guanine

question
4 bases in RNa
answer

adenine

 

uracil

 

cytosine

 

guanine

question
Diff in chemical structure of nucleotide and nucleoside
answer
no phosphate group is attached to a nucleoside
question
Difference in chemical structure of ribonucleotide and deoxyribonucleotide
answer

ribose has -OH at 2' C in pentose sugar

 

deoxy doesn't

question
What is difference in chemical structure of purine and pyrimidine?
answer

different nitrogenous bases

 

purine: 2 C-rings

 

pyrimidine - 1 C-ring

question
which bases purines?
answer
adenine and guanine
question
Which bases pyrimidines?
answer
cytosine, thymine, uracil (CUT)
question
3 components of nucleotide
answer

nitrogenous base

 

pentose sugar

 

phosphate group

question
What purpose does enzyme phosphorylation serve?
answer
regulation of activity and turn pathways on/off
question
After ATP and GTP cyclized to form cAMP and cGMP, what is their role?
answer
regulate cellular processes through enzyme activation/deactivation
question
Arsenate can substitute for phosphate of ATP. Arsenate undergoes spontaneous hydrolysis w/o enzymes. What property of ATP as ideal storage does this spoil?
answer

stability

 

ability to form high energy phosphate bonds

question
What are [ ] of conjugate acid/base when pH = pK?
answer
[conjugate acid/base] are equal to each other (50/50) in solution
question
What is Henderson-Hasselback equation? How would a doctor use it?
answer

pH = pK' + log [base]/[acid]

 

Doctor could use it to relate [ ] of each of the conjugated acid/base pairs to the pH of its surrounding enviro

question
How are "acid" + "base" described in biological systems?
answer

acid - proton donor

 

base - proton acceptor

question
What are pKs of bicarbonate and phosphate systems?
answer

bicarbonate~6.1

 

phosphate~6.7

question

Two most impt. buffer systems in body?

 

Which buffer system is more impt and why?

answer

phosphate and bicarbonate

 

bicarbonate is more important because there is a greater [bicarbonate] in the body

question
How does H+ effect biological systems?
answer

rate of rxns

 

membrane permeability

 

molecule stability and native conformations of proteins and macromolecules

 

rate of transport through membranes

 

drug properties

 

hydrophobicity/hydrophilicity of compound

question
Equilibrium Constant
answer

Keq = [H+][A-]/ [HA}

 

relate [ion] w/ [aqueous compound]

 

measure of dissociation of compound into ionic components

 

question

What is H3O+?

 

answer
hydronium ion
question
Characteristics of H2O responsible for behavior
answer

dipolar

 

H bonds

 

↑ than normal bp for mw

 

↑ than normal fp

 

↑ heat capacity

 

density solid < density liquid (ice floats on liquid H2O)

question
What rxns do proteins containing S- undergo
answer
sulfahydryl groups oxidized to form disulfide linkages (cysteine)
question
AA-related cause of pellagra
answer
lack of trp
question
What AAs contain S?
answer

met

 

cys

question
What AAs have -OH groups on sidechain?
answer

ser

 

thr

 

tyr

question
Disorders that arise from defects in tyr metabolism?
answer

tyrosinosis

 

albinism

 

alcaptonuria

question
Disorder that arises from defects in phe metabolism?
answer
phenylketonuria
question
Defects in metabolism of which AAs leads to maple syrup urine disease?
answer

val

 

leu

 

pro

 

 

question
Acidic AAs
answer

glu

 

asp

 

asn

 

gln

question
Basic AAs
answer

lys

 

arg

 

his

question
AAs w/ aromatic sidechains
answer

phe

 

tyr

 

trp

question
AAs w/ aliphatic sidechains
answer

pro

 

ile

 

gly

 

val

 

ala

 

leu

question
Two Ex of Differences Between Identical Twins that Illustrate that Environment plays a role in development and health
answer

fingerprints are different of two twins - different positions in womb

 

type I diabetes - if one gets, less than 1/2 the time other twin gets

question

What percentage of live births suffer from a disease causing monogenic defect?

 

answer
1/100 or 1% of libe births suffer from a monogenic defect
question
What percentage of live births suffer from a disease-causing chromosomal abnormality?
answer
1/1000 or 0.1% of live births suffer from a disease-causing chromosomal abnormality
question
How many of the chromosomes are X chromosomes?
answer

normal female - 2 X chromosomes

 

normal male - 1 X chromosome

question
How many chromosomes are Y chromosomes?
answer

normal female - 0 Y chromosomes

 

normal male - 1 Y chromosome

question
How many of the chromosomes are considered autosomes?
answer
44 (22 from father, 22 from mother)
question
What is an autosome?
answer
a chromosome that is not a sex chromosome
question
4 trisomies for which live birth are possible
answer

trisomy 13

 

trisomy 18

 

trisomy 21

 

trisomy X

 

XYY

question
Which of the 4 trisomies produces mild to undetectable symptoms?
answer

trisomy XYY

 

trisomy XXX

question
Which trisomy is otherwise known as Down's syndrome?
answer
trisomy 21
question
What is XYY syndrome?
answer

tall

 

other mild symptoms

question
What is Klinefelter's Syndrome?
answer

male

 

testicular failure

 

can't conceive

question
What is Turner's Syndrome?
answer

X-

 

sexually immature

 

short

 

web neck

 

phenotypically female

question
How does x-linked disease inheritance differ from inheritance of an autosomal disease?
answer

lack of male to male transmission

 

gender-dependent

 

x-linked gene comes from mother on X chromosome only, but can affect both males and females, through mostly males show disease

 

autosomal come from chromosomes other than sex chromosome

question
How does inheritance of a mitochondrial disease differ from the inheritance of an autosomal disease?
answer

An autosomal disease passes on one allele from the mother and one allele from the father

 

A mitochrondrial disease has only one allele from the female/mother only and all offspring will show some degree of the disease

question

Which will probably have greatest number of offspring who suffer from an inherited disease (may be more than one):

 

A. parents both heterozygous for autosomal recessive disease

 

B. parents both heterozygous for an autosomal dominant disease

 

C. a father who suffers from an X-linked recessive disease and a mother who is homozygous wild type (has only well type of disease gene)

 

D. a mother who is heterozygous for an x-linked recessive disease and a father who is wild type hemizygous (has the well form of that disease gene)

 

E. a father who suffers from a mitochondrial disease and a mother who does not at all have it

 

 

answer
B. parents both heterozygous for a dominant disease will have greatest # of offspring
question

Of these, which will probably have the least number of offspring who suffer from an inherited disease (may be more than one):

 

A. parents both heterozygous for autosomal recessive disease

 

B. parents both heterozygous for an autosomal dominant disease

 

C. a father who suffers from an X-linked recessive disease and a mother who is homozygous wild type (has only well type of disease gene)

 

D. a mother who is heterozygous for an x-linked recessive disease and a father who is wild type hemizygous (has the well form of that disease gene)

 

E. a father who suffers from a mitochondrial disease and a mother who does not have it

 

 

answer

E. a male who suffers from mitochondrial disease and a female who does not

 

C. a father who suffers from an x-linked recessive disease and a mother who is homozygous wild type (has only well type of disease gene)

question
Explain how penetrance might mean that individuals with disease symptoms might not be observed in a pedigree
answer
Just because genotypically the person has the disease doesn't mean they express it phenotypically
question

Genotype?

 

Phenotype?

answer

genotype-genetic makeup

 

phenotype-physical manifestation

question
How does penetrance affect onset of hereditary hemochromatosis?
answer

used to be thought rare

 

now known as the most common hereditary disease in the USA

question
What environmental factors affect the onset of hereditary hemochromatosis?
answer

gender - females under 50 not have disease (menstrual cycle expels excess iron)

 

blood donations

 

diet - not enough Fe normally and you make most of Fe intake

 

alcohol consumption

 

environment

question
Why does an X-linked disease such as Duchenne muscular dystrophy seldom cause symptoms in females?
answer

X-inactivation and that males with the defect do not reproduce.

 

Females need both x's to be defective in order the x-recessive diseases to show

 

females have two x's

question
A newly inherited disease has been discovered in which the disease ocuurs only when the defect is inherited from the father. The disease gene has what pattern of genetic inheritance?
answer
imprinted
question
Which is meant by "a genetic disease is never inherited"?
answer
A defect that if inherited would prevent the survival of the fetus and/or prevent reproduction of the fetus
question
What disease is a genetic disease in which the mutations that cause it often occur after birth?
answer
cancer
question
Tay Sachs inheritance type
answer
autosomal recessive
question
cystic fibrosis inheritance type
answer
autosomal recessive
question
sickle cell anemia inheritance type
answer
autosomal recessive
question
Huntington disease inheritance type
answer
autosomal dominant
question
hereditary hemochromatosis type of inheritance
answer
autosomal recessive
question
Duchenne muscular dystropy inheritannce type
answer
x-linked (recessive)
question
familial hypercholesterolemia inheritance type
answer
autosomal dominant
question
Leber's hereditary optic neutopathy type of inheritance
answer
mitochondrial
question
genetic defect in Huntington disease
answer

a triplet repeat of CAG (glutamines) amino acids that encode for polyglutamine tract.

 

Normally - ≤ 34

 

Have Disease - ≥ 37

question
most common inherited disease in the USA
answer
hereditary hemochromatosis
question
Is hereditary hemochromatosis fatal w/o txt?
answer
yes
question
most common lethal inherited disease
answer
cystic fibrosis
question
What protein in defective in cystic fibrosis?
answer
CFTR (Cl- transporter)
question
Is what organ is the defect of cystic fibrosis most problematic?
answer
lungs
question
What problem generally causes death in cystic fibrosis?
answer

lung infections caused by P. aeroginosa

 

accumulates in lungs and destroys lining

question
What does the protein involved in cystic fibrosis do to promote the eventually fatal action that happens?
answer

CFTR used to clear out bacteria from lungs

 

dysfunctional in CF and can't remove bacteria anymore

 

lungs get destoyed by inhaled bacteria (P. aeroginosa)

question
2 inherited diseases that protect against infectious disease and what they protect against
answer

cystic fibrosis - protect from typhoid fever

 

sickle cell anemia - protects from malaria

question
Enzyme defective in Tay Sachs disease
answer
hexosaminidase A
question
What builds up and where does it build up in Tay Sachs?
answer
glycosphinogolipids build up in the brain
question
What are the symptoms of Tay Sachs?
answer

mental retardation

 

blindness

 

paralysis

 

muscle atrophy

 

cherry red spot on retina

question
Is hexosaminidase A the only enzyme that is involved in trimming sugars off glycosphinolipids that is defective in disease?
answer
no
question
What is class of diseases that involve defective enzymes involved in trimming sugars off of glycosphingolipids?
answer
sphinogolipid storage disorders
question
3 monogenic or polygenic diseases
answer

hypertension

 

cardiovascular disease

 

type 2 diabetes

question
Only polygenic diseases
answer

anencephaly

 

spina bifida

 

cleft lip/palate

 

alchoholism

 

asthma

 

bipolar disorder

 

inherited epilepsy

 

idiopathic gout

 

obesity

 

schizophrenizia

 

type I diabetes

question
3 inherited monogenic diseases that cause hypertension
answer

glucocorticoid-remediable aldosteronism

 

apparent mineralocorticoid excess

 

Liddle syndrome

question
polygenic syndrome that is generally considered cause of most hypertension
answer
essential hypertension
question
3 genes that have been associated with type 1 diabetes
answer
3 HLA genes
question
Name genes that have been associated with a monogenic disease that may be though of as type 2 diabetes
answer
MODY 1-7
question
3 genes that have been associated with polygenic type 2 diabetes
answer

PPAR-gamma

 

glucokinase

 

calpain 10

question
Are all individuals with a defect in one of the genes associated with polygenic type 2 diabetes going to develop the disease?
answer
no
question
Which of these genes associated with type 2 diabetes has been found in 85% of the world population?
answer
PPAR-gamma
question

Which of the following infectious diseases is NOT thought to be protected against by an inherited genetic mutation or deletion (may be more than one):

 

A. HIV

B. typhoid fever

C. anthrax

D. malaria

E. leprosy

answer

anthrax

 

leprosy

question
What is a "snip" and with what frequency are SNPs encountered in human DNA?
answer

single nucleotide polymorphisms

 

1:300 bps

question

A patient has the form of the gene that cause Huntington's (20 repeats). The patient asks about a "gray area" in testing and whether the result in certain.

 

What do you say?

answer
some people have an intermediate number of repeats (mid-30s) but for someone with 20 repeats the test is certain.
question

You are treating a case of erythroblastosis fetalis, a disease of the fetus in pregnancy. This is most often caused by isoimmune reaction to the D antigen, which is one of the antigens responsible for the Rh blood group. Abs developed by the Rh- mother "attack" an Rh+ fetus's RBCs leading to hemolysis. You want to quickly counsel the expecting couple about the likelihood the offspring will have another Rh+ fetus. The antigen is inherited in autosomal domianant fashion so you know the mother is

homozygous for the genes that make her Rh-. The father knows he is Rh+ so you able to advise them that on avg?

 

AND

 

You ask the father if he has previously fathered an Rh- child and he says YES you are able to advise that on avg?

 

AND

 

if the father says that has  has fathered an Rh- child and he instead says NO you are able to advise that on avg?

answer

the info given you can't determine the likelihood of the disease for their future offspring

 

the info given you can't determine the likelihood of the disease for their future offspring

 

50% of their offspring will suffer from the disease

 

question

autosomal recessive homozygote

 

male and female

 

which get disease?

answer
female and male
question

autosomal recessive heterozygote

 

male and female

 

which get disease?

answer
neither
question

autosomal dominant homozygote

 

male and female

 

which get disease?

answer
both
question

autosomal dominant heterozygote

 

male and female

 

which get disease?

answer
both
question
x-linked recessive hemizygous
answer

male

 

question

x-linked recessive heterozygote

 

male and female

 

which get disease?

answer
neither
question

x-linked recessive homozygote

 

male and female

 

which get disease?

answer
female
question

Mitochondrial, only father has disease

 

male and female

 

which get disease?

answer
neither
question

Mitochondrial, only mother has disease

 

male and female

 

which get disease?

answer
Both
question
What are some ways DNA is obtained from children and adults?
answer

blood

 

saliva

 

cheek swabs

question
3 forms of prenatal diagnosis of inherited disease that utilized together cover most of period between 10 weeks of gestation through birth and rate of fetal loss associated w/ each?
answer

chorionic villus sampling (CVS) - 0.5-1.0% loss

 

ultrasound - 0% loss

 

cordocentesis- 1-2% loss

question
What does preimplantation diagnosis of in vitro eggs allow?
answer
embryo selection
question

How many inherited diseases does FL screen for?

 

What do these diseases have in common that makes them a good idea to screen for?

 

What instrument made possible the recent expansion in the number of diseases screened in FL and does it analyze sequences or metabolites?

answer

35 diseases screened in FL

 

cause early damage and effective txt exists

 

tandem mass spectrometry-analyzes metabolites

question
Advantages of screening for genetic diseases by DNA sequencing
answer

may catch a patient gives a false - by another method

 

easier, less expensive to do in quantity than biochem assays

 

heritage and fam history of person gives info about what diseases and mutations to look for

 

it is predictive (before symptom onset)

question
Disadvantages of screening by DNA sequencing
answer

false negatives due to gene mutation being in unexpected location in gene

 

limited coverage of test - only test for specific disease, might miss others

 

may have added expenses due to patented genes

question

% frequency of two most often occuring mutations in CTFR genes

 

Any high frequency mutations in familial hypercholesterimia genes?

answer

70% and 2.5%

 

no, high freq mutations in FH genes

question
Gene defect that resulted in fava beans causing health problems in Greece and primaquine causing health problems in WW2
answer
hemolytic anemia
question

Knowledge of person's VKORC1 and CYP2C9 seq can help you decide what about a patient?

 

What other seq can be screened?

answer

drug dosage and type

 

P450 screened also

 

 

question
Pharmacogenomics
answer
use sequence info to make decisions about a drug
question
A 27 y/o patient's father has been diagnosed with Huntington disease. It would be important to:
answer
tell the patient there is a test involving DNA seq to show if he will suffer from Huntington disease later in life
question
Is Cushing syndrome characterized as a cancer b/c it involves overgrowth of cells (a tumor) in the adrenal gland that produces cortisol?
answer
No, it is not metastatic
question
What can be involved in genesis of cancer and which always involved?
answer

bacteria

 

viruses

 

inherited predispositions

 

gene defects - always involved

 

enviro causes

 

question
cell cycle genes
answer
Rb and p53
question
growth signal transduction genes
answer
ras, HER2, PDGF, EGF
question
DNA repair genes
answer

hMLH1

 

hMSH2

question
BRCA-1
answer
anti-oncogene
question
Why can hEGFR be considered a protooncogene and how might become an oncogene?
answer

protooncogene b/c it is a growth-stimulating gene

 

can become oncogene if its activity starts to result in uncontrolled growth

 

 

question

Gene A loses activity w/ certain mutation.

 

Is the normal gene a tumor suppressor, oncogne, anti-oncogne, or proto-oncogene?

answer
tumor suppressor and anti-oncogene for both normal and mutant genes
question
characteristics of matrix metalloproteinases and involved in what cancerous process
answer

protein/enzymes that require a metal (Zn or Ca) ion to break down proteins in ECM of cell

 

involved in metastasis

question
Tumorigenic cells for cancer therapy
answer

only some cells in tumor can generate new tumor

 

if can treat or cut out those cells, then localize tumor and control metastasis

question
Unique Characteristic of PARs
answer
proteolytically remove N-terminus of receptor itself and new N-terminus is the ligand that activates receptor
question
Kd
answer

[ligand] for 1/2 max occupancy of receptors

 

measure affinity of ligand for receptor

question
EC50
answer

[ligand] for 1/2 max response

 

effectiveness in eliciting cellular response

question
largest superfamily of receptors
answer
GPCRs
question
What family of receptors facilitates addiction to tobacco?
answer
ionotropic nicotinic Ach-R
question
Differences and Similarities in Intracellular Receptors
answer

some reside in cytoplasm until encounter ligands-glucocorticoid and aldosterone-Rs

 

most reside full time in nucleus

 

receptor ligand complex acts on nucleus by binds to DNA and affecting expression (turn on/off expression)

question
concentration of albumin in serum
answer
4 g/dL
question
4 functions of plasma albumin
answer

fatty acid transport

 

bilirubin transport

 

transport of steroid hormones

 

transport of sulta drugs, penicillin, aspirin

question
Plasma protein degraded randomly at a rate of 100%/day. What is biological half life?
answer
0.693 days
question

most abundant alpha-1 globulin?

 

Function?

 

Clinical result of its absence?

answer

alpha-1 antiprotease

 

protease inhibitor on compounds such as elastase and collagenase

 

prevents proteolysis in lungs

 

lung loses ability to recoil after inspiration leading to emphysema and respiratory failure

question
organ albumin is synthesized in
answer
liver
question
major class of proteins NOT synthesized in liver
answer
immunoglobulins
question
most abundant of plasma proteins
answer
albumin
question
how are fatty acids transported in plasma
answer
bound to albumin
question
major fetal plasma protein
answer
alpha-1 fetoglobulin
question
plasma protein that binds and transports iron
answer
transferrin
question
plasma protein that binds and transports cortisol
answer

cortisol-binding clobulin (alpha-1 globulin)

 

 

question
plasma protein that binds and transports vitamin A derivitives
answer
retinol-binding protein (alpha-1 globulin)
question
plasma protein that binds and transports testosterone
answer

sex hormone binding globulin (SHBG)

 

beta-globulin

question
plasma protein that binds and transports bilirubin
answer
albumin
question
What ahppens to free hemoglobin in plasma?
answer
degraded by reticulothelial cells
question
What would happen to hemoglobin in plasma if haptoglobin were absent?
answer

iron would be lost due to Hb breakdown.

 

Hb is lost through the kidney and excreted in urine.

question
blue protein and what is its function
answer

ceruloplasmin

 

blue b/c of copper

 

oxidize Fe 2+ Fe 3+ in plasma

 

low levels found in Wilson's disease

question
In which human organ is myoglobin (Mb) most impt?
answer
heart b/c rapid O2 supply needed
question
Explain causes and importance of right shift in Hb/O2 binding curve
answer

right shift caused by:

 

decreased pH (increased [H+])

 

increased [CO2]

 

increased [2,3-BPG]

 

increased temperature

 

all factors lead to increased O2 unloading which means that a higher percentage of O2 is delivered to tissues

question
In Hb, how does binding of first oxygen molecule affect binding of next ones?
answer

Deoxy Hb is usually in taut (T) form where heme groups restricted and hard for O2 to bind

 

When O2 binds to 1st heme group, the Fe of that heme will shift and pull attached his along.

 

Movement breaks salt bridges pushing Hb into relaxed (R) state and allow more O2 binding sites to become available

 

 

question
What is Bohr effect?
answer

A right shift when pH decreases (increase in H+ conc.)

 

O2 release from Hb will increase when pH is lowered or [CO2] is high

 

Hb has decreased O2 affinity

 

Raising pH or decreasing [CO2]-shift curve to left

question
Physiological importance of cooperativity in Hb function
answer
Hb has 4 subunits where binding of O2 at one heme group increases the affinity for O2 of the other heme groups in the same molecule
question
Compare behavior of Mb and Hb with respect to O2, CO2, and H+
answer

Mb has a greater affinity at lower [O2] than Hb

 

Hb can transport more molecules of O2 b/c of cooperative effect of multiple binding sites

 

Hb can't readily bind 1st O2, but once it does has higher affinity for O2 at other sites

 

Hb-sigmoidal curve

 

Mb-hyperbolic

 

Hb responds more readily to small changes in partial pressures of O2

 

Mb saturated quicker than Hb at low partial pressure of O2 (doesn't have much flexibility)

question
How does protein (globin) portion of Mb or Hb affect reactivity of heme?
answer

weaken strength of heme-O2 interaction. Heme binds O2 so stronglyit can convert it to a superoxide anion, which can be an unwanted oxidizing agent

 

prevents interaction of oxy-heme groups with other oxy-heme groups

question
How and where does 2,3-BPG interact with Hb?
answer

2,3-BPG binds to deoxy Hb-makes it more stable and resistant to oxygenation after O2 delivery

 

negative charge allows BPG to bind to a site between two alpha chains

 

causes right shift in O2-dissociation curve (lower O2 release)

question
Where does 2,3-BPG come from?
answer
product of glycolytic pathway
question
How does fetal Hb (HbF) differ from HbA?
answer

Fetal Hb has two gamma chains instead of beta chains.

 

2,3-BPG can't bind to fetal Hb and it has greater affinity fo O2 and takes O2 from maternal Hb

 

HbF is left shifted on O2-dissociation curve compared to maternal Hb

 

 

question
What does Hill Eqn describe?
answer
importance of cooperativity
question
How does NO interact w/ Hb and what is physiological significance of that interaction?
answer

Hb binds NO at heme Fe and cys residues in globin chain.

 

NO relaxant for vascular smooth muscle

 

Hb can pick up NO, stiffen vascular tissues, and increase BP

 

NO is strong vasodilator so Hb can be used to mediate vascular tone

question
What is difference btwn HbS and HbA?
answer
HbA has normal beta chain while HbS has sickly cell hemoglobin. 6th AA for normal beta globin would be a glutamic residue but in HbS that Glu is replaced with a Val. Val is uncharged and allows hydrophobic pockets. The chains bind together and crystallize
question
Physiochemical/Pathological Basis for All Clinical Manifestations of Sickle Cell Disease
answer

crystallization and stiffening of Hbs causes them to adhere to the endothelium and often obstruct small vessels (capillaries) or cause hemolysis

 

hemolysis can cause anemia and hyperbilirubinemia, causing pallor and jaundice

 

Complete vasocclusion can cause ishemia or infarction resulting in organ damage

 

Stroke, infection and excrutiating pain can result

question
How is Sickle Cell Disease Inherited?
answer
recessive disorder. Only homozygous HbS cause the disease to become expressed.
question
What is an enzyme?
answer

a protein catalyst for specific biochem rxns.

 

It will not undergo chem rxnitself and can be reused for other rxns

question

What does enzyme effect and not effect in rxn?

 

 

answer

Enzymes reduce activation energy.

 

Keq and delta G are not affected by enzymes.

question
Name and describe 2 models used to describe enzyme specificity and/or catalytic activity
answer

lock and key model

 

describes an enzyme active sites (lock) being specific for binding substrate (key)

describe specificity

 

induced fit model

 

active site will conform to fit substrate

describes specificity and catalytic activity

question
What is prosthetic group?
answer

non-protein organic molecule that is tightly bound to enzyme active site

 

ex-heme, biotin, or flavin

 

holoenzyme-prosthetic group attached

 

apoenzyme-prosthetic group NOT attached

question
Name 6 Classes of Enzymes
answer

oxidoreductases-catalyze RED/OX reactions

Ex-H+ donor to substrate


transferases-transfer group from one molecule to another

Ex-phosphoylases


hydrolases-hydrolytic cleavage of bond

Ex-peptide bond cleavage


lyases-cleave bonds w/o water to leave double bond or addition of other groups to double bond

Ex-decarboxylase


isomerases-change geometry of molecule

Ex-cis-trans isomerase


ligases-join 2 molecules together though hydrolysis of high energy bond

Ex-carboxylase

question
What is Michaelis-Menton Eqn and what do terms mean?
answer

V = Vmax[S]/(Km+[S])

 

V - velocity of rxn

Vmax - max rxn velocity

[S] - substrate concentration

Km - constant value for a specific substrate

 

question
In a Michaelis-Menton plot, where is Vmax and how do you find Km?
answer

Vmax - when [S] is very high

 

Km - [S] when V = 1/2(Vmax)

question
A Lineweaver-Burk plot is also called a ---------
answer
Double-reciprocal plot
question
What is plotted on Lineweaker-Burk plot and what are the x- and y-intercepts of the plot?
answer

The LB graph plots the inverse of the Michaelis-Menten plot, which is 1/V on the y-axis and 1/[S] on the x-axis

 

x-intercept - 1/Km

 

y-intercept - 1/Vmax

question
What are advantages of the Eadie-Hofstee plot?
answer
The E-H plot gives more evenly spaced data points than the  L-B plot.
question
What characteristics distinguish a competitive inhibitor from the other types of inhibitors?
answer

bind directly to the active site and can be overcome by increased [substrate].

 

Other inhibitors bind to other sites on enzyme

question
On the Lineweaver-Burk plots are the vertical or horizontal intercepts the same or different for competitively inhibited rxns?
answer

same y-intercept

 

different x-intercepts

question
On the Lineweaver-Burk plots are the vertical or horizontal intercepts the same or different for non-competitively inhibited rxns?
answer

different y-intercepts

 

same x-intercepts

question
On the Lineweaver-Burk plots are the vertical or horizontal intercepts the same or different for uncompetitively inhibited rxns?
answer

different y-intercepts

 

different x-intercepts

question
What does inhibitor react with for competitive inhibition?
answer
active site of the enzyme
question
What does inhibitor react with for non-competitive inhibition?
answer
react with enzyme to reduce its effectiveness to bind w/ substrate
question
What does inhibitor react with for uncompetitive inhibition?
answer

bind with ES complex.

 

irreversible inhibitors.

question
Sigmoid V versus [S] plot and curved Lineweaver-Burk plots indicate
answer
allostery and positive cooperativity of the enzyme (n = 2)
question
What factors determine the amount of enzyme activity in serum?
answer

amount of tissue producing enzyme

 

rate of enzyme released

 

rate of enzyme inactivation/elimination from plasma

question
Define: Standard International Unit (SIU)
answer
1 standard international unit of enzyme activity converts 1 μM of substrate/minute
question
2 most commonly measured serum aminotransferases and describe rxns they catalyze
answer

Aspartate aminotransferase (AST) - catalyzes exhange of amino group between alpha amino acids (aspartate) and alpha keto acids

 

Alanine aminotransferase (ALT) - catalyzes exchange of amino group between alpha amino acids (alanine) and alpha keto acids

question
In which pathological states are the two most commonly measured serum aminotransferases elevated?
answer

AST - liver damage and myocardial cells,hemolysed blood

 

ALT - liver damage

question
Reaction catalyzed by γ-glutamyltranspeptidase and how it is used diagnostically?
answer

Glutathione + amino acids → γ-glutamyl-amino acid + cys-gly

 

γ-glutamyltranspeptidase found in kidney, intestine, liver, and fetal tissue

 

GGT levels are elevated and very sensitive in liver damage

 

question
2 commonly measured phosphatases and how are they used diagnostically?
answer

Alkaline phosphatase (ALP)

 

Hydrolyzez phosphate groups from organic monophosphate at pH~9

Found in liver, bone, intestine, and placental tissue

Elevation of ALP means damage to liver and bone tissue

Elevated in gowing children, bone fractures, and pregnant women

 

Acid Phosphatase

 

hydrolyzes phosphate groups from organic monophosphates at pH~5

 

found in prostate, platelets, and erythrocytes

Elevation found in metastatic prostate cancer and hemolysed blood samples

 

 

question
Diagnostic utility of LDH
answer
Used to detect MI and hemolysis
question
"flipped" LDH
answer

Most common form is LDH2 (HHHM)

 

After MI or hemolysis, LDH1 (HHHH) predominates causing a "flipped" LDH b/c LDH1>LDH2

question
What reaction does LDH catalyze?
answer

Lactate + NAD → pyruvate + NADH + H

 

interconversion of pyruvate and lactate

question

Another name for alpha hydroxybutyrate dehydrogenase (HBD)?

 

 

answer
LDH1
question
What does elevated serum HBD mean?
answer
damage to myocardial cells due to recent MI
question
Reaction catalyzed by CK (CPK)
answer
creatine phosphate + ADP → Creatine + ATP
question
Diagnostic meaning of elevated serum CK
answer

has 2 subunits, M and B

 

MB-MI or brief ischemia

 

MM-vigorous exercise, injection, convulsions

 

BB-neural tissue damage

question
Diagnostic significance of elevated serum amylase
answer

pancreatitis

 

morphine

question
Reaction catalyzed by serum amylase
answer

starch + H2O → maltose, maltotriose & limit dextrins

 

digest starch

question
Elevated serum lipase means
answer

pancreatic pathology

 

morphine

question
Reaction catalyzed by serum lipase
answer

trigylceride + H2O → fatty acids + glycerol

 

fat digestion

question
What are troponins and how are they used in diagnosis?
answer

proteins that function in the contractile apparatus of the muscle

 

Cardiac troponin I is increased in plasma 3-6 hours after MI

question
Serum Enzyme Levels in crush injury
answer

mildly elevated alkaline phosphatase (healing bone)

 

elevated creatine kinase MM (skeletal muscle)

question
Serum Enzyme Levels in vigorous exercise
answer
elevated creatine kinase MM (skeletal muscle)
question
Serum Enzyme levels in morphine injection
answer
elevation of serum amylase and lipase
question
Serum Enzyme Levels in pregnancy
answer

mildly elevated alkaline phosphatase (bone growth)

 

elevated GGT

question
Four Categories of Cell Adhesion Molecules
answer

integrins

 

immunoglobulin superfamily

 

cadherins

 

selectins

question
Which of the CAM categories would be actively involved in transmitting signals from the inside to the outisde of the cells and vice versa?
answer
integrins
question
What CAM category is involved in adherens junction between cell?
answer
cadherins
question
Abbreviations for 3 types of adhesion molecules of Ig suberfamily and tell their origins
answer

NCAM - neural cell adhesion molecule

 

PECAM - platelet-endothelial cell adhesion molecule

 

VCAM - vascular cell adhesion molecule

 

Named for their similarity in structure to the Igs

question
4 Diseases in which CAMS are involved
answer

Rheumatoid arthritis - overexpression of VCAMs

 

Psoriasis - form of an integrin

 

Pemphigus vulgaris - autoantibodies interacting with desmoglein

 

von Willebrand disease - expression of P-selectin

question
Describe alpha-helix
answer
tightly coiled, stabilized by H bonding btwn imido groups and oxygen of carbony groups, many helices (3.6 AA/turn)
question
Beta sheet
answer

regions of same chain or neighboring chains bond to each other w/ H bonds, the H bonds are perependicular to the long axis of the chain

 

most stable conformation - antiparallel sheets (one side N→C other side C→N

question
Beta turns
answer

H bonding of AA 3 sequences apart in same chain

 

results in U turn bend of chain

question
What AA usually phosphoylated in proteins?
answer

ser

 

thr

 

tyr

question
Commonly occurring modification of AA found in some proteins
answer

acetylation of N terminus

 

carboxylation - add COOH

 

hydroylation - add OH

 

glycosylation - add glucose

 

phosphorylation - add phosphate group

 

disulfide linkages

question
Primary Structure
answer
AA sequence
question
Secondary Structure
answer

alpha helix

 

beta-pleated sheets

 

beta-turns

 

random coiling

 

results from free roation of bonds besides peptide bonds

question
Tertiary Structure
answer

secondary structures fold on each other

 

hydrophobic - inside

hydrophilic - outside

question
Quarternary Structure
answer
multiple polypeptide chains interact by noncovalent bonds to form single structure
question
General Solubility Prop. of Proteins
answer

fibrous and insoluble

 

globular and soluble

 

firbrous and soluble

question
Functions of Proteins
answer

structural roles

 

enzymes

 

role in contractile structures

 

transport (Hb)

 

hormones

 

receptors

 

Abs

question
What are proteins and peptides made of?
answer

peptides - moderate chain length polymers of amino acids joined by peptide bonds

 

proteins - polymeric compounds composed of AA joined by peptide bonds

question
What is unique about peptide bond?
answer
it is rigid b/c tautomerism
question
In ABO blood group, where is difference in oligosaccharide located and how sugars different?
answer

due to presence or absence of N-acetyl-galactosamine or galactose linked to penultimate galactose by C1-C3 linkage

 

1 sugar difference

question
Glycosaminoglycans and 2 Ex
answer

unbranched polysacc w/ repeating disacc - one is AA, other is uronic acid

 

Ex - hyaluronic acid and heparin

question
3 Impt Disacc and which alpha or beta linked?
answer

maltose - alpha linked

 

sucrose - alpha linked

 

lactose - beta linked

question
3 Most Impt polysacc and what are linkages? Why is linkage impt?
answer

starch - alpha linked (spiral)

 

glycogen - 2 types - alpha C1-C4 (linear)

                                 alpha C1-C6 (branched)

 

cellulose - beta linked (linear)

 

alpha and beta linkage affects the shape of the compound and humans can't digest cellulose b/c beta linkages

question
What is glycoside?
answer

anomeric -OH group of sugar reacts w/ another -OH compound

 

 

question
aglycone
answer
compound that attaches to anomeric C of sugar
question
Name and describe 2 commonly found mod. of sugars
answer

amino sugar - -OH group replaced by amino group

Ex - glucosamine, galactosamine

 

deoxy sugar - 1 OH group replaced by H

Ex - 2-deoxyribose

question
2 conformation of 6-membered rings
answer
boat and chair
question
What is mutarotation and where does it take place?
answer

configuration changes in molecule by ring opening and closing

 

occurs at anomeric C

question
Pyran and furan are named after which sugar structures and how many Cs are in each?
answer

pyranose - 6 C ring

 

furanose - 5 C ring

question
Most Impt Monosacc and Polysacc made up of this monosacc
answer

glucose - most impt monosacc

 

Polysacc made up of glucose - starch

                                             cellulose

                                             glycogen

question
What are aldoses?
answer
monosaccharides w/ aldehyde group
question
What are ketoses?
answer
monosaccharides w/ ketone group
question
What are carbohydrates?
answer
polyhydroxy aldehydes or ketones or compounts that can by hydrolyzed to these
question
4 Types of Compounds of which AAs are precursors
answer

hormones

 

nucleotides

 

neurotransmitters

 

AAs

question
Essential AA
answer

Pvt. Tim Hall

 

Phe

Val

Thr

 

Trp

Ile

Met

 

His

Arg

Leu

Lys

question
What is nucleotide not found in DNA or RNA that has role in energy metabolism?
answer
NAD+
question
Patient given adenosine during cardiac arrythmia. EKG during adenosine txt show AV block. If adenosine discontinuation does work, what will?
answer
theophylline
question
Nucleoside more useful that nucleotide as a drug b/c
answer
nucleoside does not have phosphate group, which restricts movement inside body
question
Biochemical mechanism that enables coffee-drinking college student to stay awake
answer

caffeine is competitive antagonist of adenosine receptor.

 

Blocks depressant action of adenosine-R and is therefore a stimulant

question
What is the modification of a normal base found in mRNA?
answer
methylated guanine
question
What is mod of a normal DNA base that affects gene expression?
answer
methylated cytosine
question
What happens when DNA exposed to 94 degrees C temperature during PCR?
answer
denaturation and 2 strands separate
question
What does it mean that DNA strands are "antiparallel"?
answer

strands run in opposite directions

 

one strand goes 3'5'

 

other strand goes 5'3'

question

Number of H bonds between A and T

 

Number of H bonds between G and C

answer

A-T : 2 bonds

 

G-C: 3 bonds

question
Difference between nucleotide and nucleic acid
answer

nucleotide - 1 molecule w/ phosphate group, base, and sugar

 

nucleic acid-several nucleotides connected w/ phosphodiester bonds

question
What 4 bases in DNA
answer

adenine

 

thymine

 

cystosine

 

guanine

question
4 bases in RNa
answer

adenine

 

uracil

 

cytosine

 

guanine

question
Diff in chemical structure of nucleotide and nucleoside
answer
no phosphate group is attached to a nucleoside
question
Difference in chemical structure of ribonucleotide and deoxyribonucleotide
answer

ribose has -OH at 2' C in pentose sugar

 

deoxy doesn't

question
What is difference in chemical structure of purine and pyrimidine?
answer

different nitrogenous bases

 

purine: 2 C-rings

 

pyrimidine - 1 C-ring

question
which bases purines?
answer
adenine and guanine
question
Which bases pyrimidines?
answer
cytosine, thymine, uracil (CUT)
question
3 components of nucleotide
answer

nitrogenous base

 

pentose sugar

 

phosphate group

question
What purpose does enzyme phosphorylation serve?
answer
regulation of activity and turn pathways on/off
question
After ATP and GTP cyclized to form cAMP and cGMP, what is their role?
answer
regulate cellular processes through enzyme activation/deactivation
question
Arsenate can substitute for phosphate of ATP. Arsenate undergoes spontaneous hydrolysis w/o enzymes. What property of ATP as ideal storage does this spoil?
answer

stability

 

ability to form high energy phosphate bonds

question
What are [ ] of conjugate acid/base when pH = pK?
answer
[conjugate acid/base] are equal to each other (50/50) in solution
question
What is Henderson-Hasselback equation? How would a doctor use it?
answer

pH = pK' + log [base]/[acid]

 

Doctor could use it to relate [ ] of each of the conjugated acid/base pairs to the pH of its surrounding enviro

question
How are "acid" + "base" described in biological systems?
answer

acid - proton donor

 

base - proton acceptor

question
What are pKs of bicarbonate and phosphate systems?
answer

bicarbonate~6.1

 

phosphate~6.7

question

Two most impt. buffer systems in body?

 

Which buffer system is more impt and why?

answer

phosphate and bicarbonate

 

bicarbonate is more important because there is a greater [bicarbonate] in the body

question
How does H+ effect biological systems?
answer

rate of rxns

 

membrane permeability

 

molecule stability and native conformations of proteins and macromolecules

 

rate of transport through membranes

 

drug properties

 

hydrophobicity/hydrophilicity of compound

question
Equilibrium Constant
answer

Keq = [H+][A-]/ [HA}

 

relate [ion] w/ [aqueous compound]

 

measure of dissociation of compound into ionic components

 

question

What is H3O+?

 

answer
hydronium ion
question
Characteristics of H2O responsible for behavior
answer

dipolar

 

H bonds

 

↑ than normal bp for mw

 

↑ than normal fp

 

↑ heat capacity

 

density solid < density liquid (ice floats on liquid H2O)

question
What rxns do proteins containing S- undergo
answer
sulfahydryl groups oxidized to form disulfide linkages (cysteine)
question
AA-related cause of pellagra
answer
lack of trp
question
What AAs contain S?
answer

met

 

cys

question
What AAs have -OH groups on sidechain?
answer

ser

 

thr

 

tyr

question
Disorders that arise from defects in tyr metabolism?
answer

tyrosinosis

 

albinism

 

alcaptonuria

question
Disorder that arises from defects in phe metabolism?
answer
phenylketonuria
question
Defects in metabolism of which AAs leads to maple syrup urine disease?
answer

val

 

leu

 

pro

 

 

question
Acidic AAs
answer

glu

 

asp

 

asn

 

gln

question
Basic AAs
answer

lys

 

arg

 

his

question
AAs w/ aromatic sidechains
answer

phe

 

tyr

 

trp

question
AAs w/ aliphatic sidechains
answer

pro

 

ile

 

gly

 

val

 

ala

 

leu

question
Two Ex of Differences Between Identical Twins that Illustrate that Environment plays a role in development and health
answer

fingerprints are different of two twins - different positions in womb

 

type I diabetes - if one gets, less than 1/2 the time other twin gets

question

What percentage of live births suffer from a disease causing monogenic defect?

 

answer
1/100 or 1% of libe births suffer from a monogenic defect
question
What percentage of live births suffer from a disease-causing chromosomal abnormality?
answer
1/1000 or 0.1% of live births suffer from a disease-causing chromosomal abnormality
question
How many of the chromosomes are X chromosomes?
answer

normal female - 2 X chromosomes

 

normal male - 1 X chromosome

question
How many chromosomes are Y chromosomes?
answer

normal female - 0 Y chromosomes

 

normal male - 1 Y chromosome

question
How many of the chromosomes are considered autosomes?
answer
44 (22 from father, 22 from mother)
question
What is an autosome?
answer
a chromosome that is not a sex chromosome
question
4 trisomies for which live birth are possible
answer

trisomy 13

 

trisomy 18

 

trisomy 21

 

trisomy X

 

XYY

question
Which of the 4 trisomies produces mild to undetectable symptoms?
answer

trisomy XYY

 

trisomy XXX

question
Which trisomy is otherwise known as Down's syndrome?
answer
trisomy 21
question
What is XYY syndrome?
answer

tall

 

other mild symptoms

question
What is Klinefelter's Syndrome?
answer

male

 

testicular failure

 

can't conceive

question
What is Turner's Syndrome?
answer

X-

 

sexually immature

 

short

 

web neck

 

phenotypically female

question
How does x-linked disease inheritance differ from inheritance of an autosomal disease?
answer

lack of male to male transmission

 

gender-dependent

 

x-linked gene comes from mother on X chromosome only, but can affect both males and females, through mostly males show disease

 

autosomal come from chromosomes other than sex chromosome

question
How does inheritance of a mitochondrial disease differ from the inheritance of an autosomal disease?
answer

An autosomal disease passes on one allele from the mother and one allele from the father

 

A mitochrondrial disease has only one allele from the female/mother only and all offspring will show some degree of the disease

question

Which will probably have greatest number of offspring who suffer from an inherited disease (may be more than one):

 

A. parents both heterozygous for autosomal recessive disease

 

B. parents both heterozygous for an autosomal dominant disease

 

C. a father who suffers from an X-linked recessive disease and a mother who is homozygous wild type (has only well type of disease gene)

 

D. a mother who is heterozygous for an x-linked recessive disease and a father who is wild type hemizygous (has the well form of that disease gene)

 

E. a father who suffers from a mitochondrial disease and a mother who does not at all have it

 

 

answer
B. parents both heterozygous for a dominant disease will have greatest # of offspring
question

Of these, which will probably have the least number of offspring who suffer from an inherited disease (may be more than one):

 

A. parents both heterozygous for autosomal recessive disease

 

B. parents both heterozygous for an autosomal dominant disease

 

C. a father who suffers from an X-linked recessive disease and a mother who is homozygous wild type (has only well type of disease gene)

 

D. a mother who is heterozygous for an x-linked recessive disease and a father who is wild type hemizygous (has the well form of that disease gene)

 

E. a father who suffers from a mitochondrial disease and a mother who does not have it

 

 

answer

E. a male who suffers from mitochondrial disease and a female who does not

 

C. a father who suffers from an x-linked recessive disease and a mother who is homozygous wild type (has only well type of disease gene)

question
Explain how penetrance might mean that individuals with disease symptoms might not be observed in a pedigree
answer
Just because genotypically the person has the disease doesn't mean they express it phenotypically
question

Genotype?

 

Phenotype?

answer

genotype-genetic makeup

 

phenotype-physical manifestation

question
How does penetrance affect onset of hereditary hemochromatosis?
answer

used to be thought rare

 

now known as the most common hereditary disease in the USA

question
What environmental factors affect the onset of hereditary hemochromatosis?
answer

gender - females under 50 not have disease (menstrual cycle expels excess iron)

 

blood donations

 

diet - not enough Fe normally and you make most of Fe intake

 

alcohol consumption

 

environment

question
Why does an X-linked disease such as Duchenne muscular dystrophy seldom cause symptoms in females?
answer

X-inactivation and that males with the defect do not reproduce.

 

Females need both x's to be defective in order the x-recessive diseases to show

 

females have two x's

question
A newly inherited disease has been discovered in which the disease ocuurs only when the defect is inherited from the father. The disease gene has what pattern of genetic inheritance?
answer
imprinted
question
Which is meant by "a genetic disease is never inherited"?
answer
A defect that if inherited would prevent the survival of the fetus and/or prevent reproduction of the fetus
question
What disease is a genetic disease in which the mutations that cause it often occur after birth?
answer
cancer
question
Tay Sachs inheritance type
answer
autosomal recessive
question
cystic fibrosis inheritance type
answer
autosomal recessive
question
sickle cell anemia inheritance type
answer
autosomal recessive
question
Huntington disease inheritance type
answer
autosomal dominant
question
hereditary hemochromatosis type of inheritance
answer
autosomal recessive
question
Duchenne muscular dystropy inheritannce type
answer
x-linked (recessive)
question
familial hypercholesterolemia inheritance type
answer
autosomal dominant
question
Leber's hereditary optic neutopathy type of inheritance
answer
mitochondrial
question
genetic defect in Huntington disease
answer

a triplet repeat of CAG (glutamines) amino acids that encode for polyglutamine tract.

 

Normally - ≤ 34

 

Have Disease - ≥ 37

question
most common inherited disease in the USA
answer
hereditary hemochromatosis
question
Is hereditary hemochromatosis fatal w/o txt?
answer
yes
question
most common lethal inherited disease
answer
cystic fibrosis
question
What protein in defective in cystic fibrosis?
answer
CFTR (Cl- transporter)
question
Is what organ is the defect of cystic fibrosis most problematic?
answer
lungs
question
What problem generally causes death in cystic fibrosis?
answer

lung infections caused by P. aeroginosa

 

accumulates in lungs and destroys lining

question
What does the protein involved in cystic fibrosis do to promote the eventually fatal action that happens?
answer

CFTR used to clear out bacteria from lungs

 

dysfunctional in CF and can't remove bacteria anymore

 

lungs get destoyed by inhaled bacteria (P. aeroginosa)

question
2 inherited diseases that protect against infectious disease and what they protect against
answer

cystic fibrosis - protect from typhoid fever

 

sickle cell anemia - protects from malaria

question
Enzyme defective in Tay Sachs disease
answer
hexosaminidase A
question
What builds up and where does it build up in Tay Sachs?
answer
glycosphinogolipids build up in the brain
question
What are the symptoms of Tay Sachs?
answer

mental retardation

 

blindness

 

paralysis

 

muscle atrophy

 

cherry red spot on retina

question
Is hexosaminidase A the only enzyme that is involved in trimming sugars off glycosphinolipids that is defective in disease?
answer
no
question
What is class of diseases that involve defective enzymes involved in trimming sugars off of glycosphingolipids?
answer
sphinogolipid storage disorders
question
3 monogenic or polygenic diseases
answer

hypertension

 

cardiovascular disease

 

type 2 diabetes

question
Only polygenic diseases
answer

anencephaly

 

spina bifida

 

cleft lip/palate

 

alchoholism

 

asthma

 

bipolar disorder

 

inherited epilepsy

 

idiopathic gout

 

obesity

 

schizophrenizia

 

type I diabetes

question
3 inherited monogenic diseases that cause hypertension
answer

glucocorticoid-remediable aldosteronism

 

apparent mineralocorticoid excess

 

Liddle syndrome

question
polygenic syndrome that is generally considered cause of most hypertension
answer
essential hypertension
question
3 genes that have been associated with type 1 diabetes
answer
3 HLA genes
question
Name genes that have been associated with a monogenic disease that may be though of as type 2 diabetes
answer
MODY 1-7
question
3 genes that have been associated with polygenic type 2 diabetes
answer

PPAR-gamma

 

glucokinase

 

calpain 10

question
Are all individuals with a defect in one of the genes associated with polygenic type 2 diabetes going to develop the disease?
answer
no
question
Which of these genes associated with type 2 diabetes has been found in 85% of the world population?
answer
PPAR-gamma
question

Which of the following infectious diseases is NOT thought to be protected against by an inherited genetic mutation or deletion (may be more than one):

 

A. HIV

B. typhoid fever

C. anthrax

D. malaria

E. leprosy

answer

anthrax

 

leprosy

question
What is a "snip" and with what frequency are SNPs encountered in human DNA?
answer

single nucleotide polymorphisms

 

1:300 bps

question

A patient has the form of the gene that cause Huntington's (20 repeats). The patient asks about a "gray area" in testing and whether the result in certain.

 

What do you say?

answer
some people have an intermediate number of repeats (mid-30s) but for someone with 20 repeats the test is certain.
question

You are treating a case of erythroblastosis fetalis, a disease of the fetus in pregnancy. This is most often caused by isoimmune reaction to the D antigen, which is one of the antigens responsible for the Rh blood group. Abs developed by the Rh- mother "attack" an Rh+ fetus's RBCs leading to hemolysis. You want to quickly counsel the expecting couple about the likelihood the offspring will have another Rh+ fetus. The antigen is inherited in autosomal domianant fashion so you know the mother is

homozygous for the genes that make her Rh-. The father knows he is Rh+ so you able to advise them that on avg?

 

AND

 

You ask the father if he has previously fathered an Rh- child and he says YES you are able to advise that on avg?

 

AND

 

if the father says that has  has fathered an Rh- child and he instead says NO you are able to advise that on avg?

answer

the info given you can't determine the likelihood of the disease for their future offspring

 

the info given you can't determine the likelihood of the disease for their future offspring

 

50% of their offspring will suffer from the disease

 

question

autosomal recessive homozygote

 

male and female

 

which get disease?

answer
female and male
question

autosomal recessive heterozygote

 

male and female

 

which get disease?

answer
neither
question

autosomal dominant homozygote

 

male and female

 

which get disease?

answer
both
question

autosomal dominant heterozygote

 

male and female

 

which get disease?

answer
both
question
x-linked recessive hemizygous
answer

male

 

question

x-linked recessive heterozygote

 

male and female

 

which get disease?

answer
neither
question

x-linked recessive homozygote

 

male and female

 

which get disease?

answer
female
question

Mitochondrial, only father has disease

 

male and female

 

which get disease?

answer
neither
question

Mitochondrial, only mother has disease

 

male and female

 

which get disease?

answer
Both
question
What are some ways DNA is obtained from children and adults?
answer

blood

 

saliva

 

cheek swabs

question
3 forms of prenatal diagnosis of inherited disease that utilized together cover most of period between 10 weeks of gestation through birth and rate of fetal loss associated w/ each?
answer

chorionic villus sampling (CVS) - 0.5-1.0% loss

 

ultrasound - 0% loss

 

cordocentesis- 1-2% loss

question
What does preimplantation diagnosis of in vitro eggs allow?
answer
embryo selection
question

How many inherited diseases does FL screen for?

 

What do these diseases have in common that makes them a good idea to screen for?

 

What instrument made possible the recent expansion in the number of diseases screened in FL and does it analyze sequences or metabolites?

answer

35 diseases screened in FL

 

cause early damage and effective txt exists

 

tandem mass spectrometry-analyzes metabolites

question
Advantages of screening for genetic diseases by DNA sequencing
answer

may catch a patient gives a false - by another method

 

easier, less expensive to do in quantity than biochem assays

 

heritage and fam history of person gives info about what diseases and mutations to look for

 

it is predictive (before symptom onset)

question
Disadvantages of screening by DNA sequencing
answer

false negatives due to gene mutation being in unexpected location in gene

 

limited coverage of test - only test for specific disease, might miss others

 

may have added expenses due to patented genes

question

% frequency of two most often occuring mutations in CTFR genes

 

Any high frequency mutations in familial hypercholesterimia genes?

answer

70% and 2.5%

 

no, high freq mutations in FH genes

question
Gene defect that resulted in fava beans causing health problems in Greece and primaquine causing health problems in WW2
answer
hemolytic anemia
question

Knowledge of person's VKORC1 and CYP2C9 seq can help you decide what about a patient?

 

What other seq can be screened?

answer

drug dosage and type

 

P450 screened also

 

 

question
Pharmacogenomics
answer
use sequence info to make decisions about a drug
question
A 27 y/o patient's father has been diagnosed with Huntington disease. It would be important to:
answer
tell the patient there is a test involving DNA seq to show if he will suffer from Huntington disease later in life
question
Is Cushing syndrome characterized as a cancer b/c it involves overgrowth of cells (a tumor) in the adrenal gland that produces cortisol?
answer
No, it is not metastatic
question
What can be involved in genesis of cancer and which always involved?
answer

bacteria

 

viruses

 

inherited predispositions

 

gene defects - always involved

 

enviro causes

 

question
cell cycle genes
answer
Rb and p53
question
growth signal transduction genes
answer
ras, HER2, PDGF, EGF
question
DNA repair genes
answer

hMLH1

 

hMSH2

question
BRCA-1
answer
anti-oncogene
question
Why can hEGFR be considered a protooncogene and how might become an oncogene?
answer

protooncogene b/c it is a growth-stimulating gene

 

can become oncogene if its activity starts to result in uncontrolled growth

 

 

question

Gene A loses activity w/ certain mutation.

 

Is the normal gene a tumor suppressor, oncogne, anti-oncogne, or proto-oncogene?

answer
tumor suppressor and anti-oncogene for both normal and mutant genes
question
characteristics of matrix metalloproteinases and involved in what cancerous process
answer

protein/enzymes that require a metal (Zn or Ca) ion to break down proteins in ECM of cell

 

involved in metastasis

question
Tumorigenic cells for cancer therapy
answer

only some cells in tumor can generate new tumor

 

if can treat or cut out those cells, then localize tumor and control metastasis

question
Unique Characteristic of PARs
answer
proteolytically remove N-terminus of receptor itself and new N-terminus is the ligand that activates receptor
question
Kd
answer

[ligand] for 1/2 max occupancy of receptors

 

measure affinity of ligand for receptor

question
EC50
answer

[ligand] for 1/2 max response

 

effectiveness in eliciting cellular response

question
largest superfamily of receptors
answer
GPCRs
question
What family of receptors facilitates addiction to tobacco?
answer
ionotropic nicotinic Ach-R
question
Differences and Similarities in Intracellular Receptors
answer

some reside in cytoplasm until encounter ligands-glucocorticoid and aldosterone-Rs

 

most reside full time in nucleus

 

receptor ligand complex acts on nucleus by binds to DNA and affecting expression (turn on/off expression)

question
concentration of albumin in serum
answer
4 g/dL
question
4 functions of plasma albumin
answer

fatty acid transport

 

bilirubin transport

 

transport of steroid hormones

 

transport of sulta drugs, penicillin, aspirin

question
Plasma protein degraded randomly at a rate of 100%/day. What is biological half life?
answer
0.693 days
question

most abundant alpha-1 globulin?

 

Function?

 

Clinical result of its absence?

answer

alpha-1 antiprotease

 

protease inhibitor on compounds such as elastase and collagenase

 

prevents proteolysis in lungs

 

lung loses ability to recoil after inspiration leading to emphysema and respiratory failure

question
organ albumin is synthesized in
answer
liver
question
major class of proteins NOT synthesized in liver
answer
immunoglobulins
question
most abundant of plasma proteins
answer
albumin
question
how are fatty acids transported in plasma
answer
bound to albumin
question
major fetal plasma protein
answer
alpha-1 fetoglobulin
question
plasma protein that binds and transports iron
answer
transferrin
question
plasma protein that binds and transports cortisol
answer

cortisol-binding clobulin (alpha-1 globulin)

 

 

question
plasma protein that binds and transports vitamin A derivitives
answer
retinol-binding protein (alpha-1 globulin)
question
plasma protein that binds and transports testosterone
answer

sex hormone binding globulin (SHBG)

 

beta-globulin

question
plasma protein that binds and transports bilirubin
answer
albumin
question
What ahppens to free hemoglobin in plasma?
answer
degraded by reticulothelial cells
question
What would happen to hemoglobin in plasma if haptoglobin were absent?
answer

iron would be lost due to Hb breakdown.

 

Hb is lost through the kidney and excreted in urine.

question
blue protein and what is its function
answer

ceruloplasmin

 

blue b/c of copper

 

oxidize Fe 2+ Fe 3+ in plasma

 

low levels found in Wilson's disease

question
Antiport
answer
molecules transported simultaneously in opposite directions
question
symport
answer
molecules transported simultaneously in same direction
question
uniport
answer
one molecule type is transported
question
primary active transport
answer

driven directly by release of energy

 

ATP hydrolysis

question
secondary active transport
answer

driven by large favorable gradient but the molecule described moves against a small unfavorable gradient

 

uses energy derived from pumping other ions to fuel its own movement

question
passive facilitated diffusion
answer
driven by a favorable gradient and uses a transport protein to get across the membrane
question
simple diffusion
answer
driven by a favorable gradient and does not require a transport protein to get through the membrane
question
Give an example of a hormone that is released in response to sensing a condition by the same tissue that synthesizes and secretes the hormone
answer
insulin is released by the pancreas in response to low blood sugar
question
Some hormones involve a complicated stimulation, a cascade involving sensing of the stimulus, release of a factor from one tissue, the hormone stmulates release of another factor from another tissue. Name a hormone that is an example of this, the tissue the hormone is secreted from, and its stimulus.
answer
cortisol is released by the adrenal cortex in response to stress
question

Two hormones that largely control blood glucose.

 

Which is released in response to high blood glucose?

 

Which is released in response to low blood glucose?

answer

insulin and glucagon

 

insulin is released in response to high blood glucose and brings blood glucose levels down

 

glucagon is released in response to low blood glucose levels and brings blood glucose levels up

question

What is circulating form of carbs in animals?

 

Storage form of carbs in animals?

 

Aerobic pathway of carb degradation that produces energy?

 

Anaerobic pathway pathway of carb degradation that produces energy?

 

Pathway of glucose synthesis?

answer

glucose

 

glycogen

 

glycolysis accompanied to TCA cycle coupled with oxidative phosphorylation

 

glycolysis diverted to form lactic acid

 

gluconeogenesis

 

question

Which of the following NOT directly required for synthesis of nucleotides?

 

A. carbohydrate

B. amino acid

C. fatty acid

answer
C. fatty acid
question
Pathway that is involved in degrading carboxylic acid group group on amino acids?
answer
urea cycle
question
Chem process by which energy is obtained from biological fuels such as the carbon skeletons of carbs, fatty acids, or amino acids (or any fuel)?
answer
oxidation
question

Organ that is the "brain" of metabolism

 

Organ that has priority over all others for supply of fuel

 

Why other tissues called extrahepatic tissues with respect to metabolism?

answer

liver

 

brain

 

b/c liver is so impt to metabolism

question
Organ that is king of metabolism
answer
brain
question

Fatblox is a drug that cannot be absorbed by cells in dig tract or cells lining blood vessels. Fatblox binds fats, thus preventing their absorption. When Fatblox is taken as a pill, you find that it prevents fats from being absorbed by the intestine, but the adipose tissues of those who take it shrink only a little. When Fatblox is given by IV into the circulation, adipose tissue shrinks drastically.

 

Explain and what are drawbacks to its use in IV form.

answer

Other organs can interconvert molecules to make fats

 

Fatblox can inhibit the transport of lipid signaling molecules by binding to them, preventing them from reaching their targets, could cause problems

question
Why can't brain use fatty acids as fuel for energy?
answer
blood brain barrier blocks them
question
What organ is most responsible for uptake and disposal of glucose from circulation and uses most glucose?
answer
skeletal muscle
question
What metabolic pathways used for energy skeletal muscles at rest and during contractile activity?
answer

In order of work rate (from high to low):

 

free ATP

 

Creatine Pi

 

glycolysis

 

fatty acids

 

 

question
Where does glycolysis take place?
answer
cytosol
question
Where does TCA cycle take place?
answer
mitochondria
question
Where does urea cycle take place?
answer
cytosol and mitochondria
question
Where are many components of plasma membrane synthesized?
answer
ER
question

The Multi-Drug Resistance gene, which encodes a protein known as p-glycoprotein, is often turned on in cancer cells. P-glycoprotein is a transporter that has the capability of pumping certain cancer drugs such as doxorubicin, daunorubicin, vinblastine and vincristine is a process driven by hydrolysis of ATP. Thus, the cancer cell is able to evade being killed by the cancer drug, even when the drug concentation outise the cell are high. This process would best be described as

 

A. primary active transport

B. secondary active transport

C. passive facilitated diffusion

D. simple diffusion

E. cannot be determined from info given

answer
A. primary active transport
question
What are difficulties in transducing a signal outside cell into cellular response inside cell?
answer
cell must be able to respond to signal and molecules causing the signal generally need to be impermeable to the cell membrane
question
Two major classifications of signal transduction (due to two major places receptors are found)?
answer

membrane receptors-cause intracellular stimulation

 

intracellular receptors-affect gene regulation

question
What is a ligand?
answer
extracellular protein that is able to bind to a specific receptor
question
What is the property of ligands that accounts for two major classifications of signal transduction?
answer
permeability of the ligand
question
Two differences between three histamine receptors in their response to histamine
answer

H1 located in endothelium and smooth muscle and causes a vasodilation effect when acted upon by an antagonist (Claritin Allegra)

Acts on sinus and allergy

 

H2 receptor is located in the stomach and causes a decrease in gastric acid secretion when acted upon by an antagonist (Zantac)

question
Ciproxifan is a potent and specific histamine H3 receptor antagonist. Would it be expected that ciprofan would alleviate allergy symtoms or suppress gastric acidity?
answer
It would not be expected to do either because the H3 receptor is located in the brain and neurons
question
2 major types of molecular switches for intracellular signaling and how is their action reversed?
answer

cAMP formation and phosphorylation

 

cAMP turned on by cyclases

turned off by phosphodiesterases

 

phosphorylation by kinases

turned off by phosphatases

question
3 ways to make a cell less responsive to adenosine receptor action even when adenosine is present in adequate amounts
answer

receptor inactivation by phosphorylation

 

receptor internalization

 

receptor degradation

question
Role of proto-oncogene ras in intracellular signal transduction
answer
small GTPase, hydrolyzes GTP
question

How do cytokines alter gene expression?

answer
bind to cytokine receptors which activate secondary messengers that activate gene expression
question
The effect of cholera toxin on signal tranduction
answer
the toxin enters the cells by riding in on a ganglioside and enters by endocytosis and inducing ADP ribosylation of G-protein. This K/O the GTPase activity that would have shut off the cyclase. Results in increases secretion, diarrhea, and death.
question
Molecule that is precursor for lipid involved in signal mediation of inflammation, blood clotting, control of vascular tone, pain, and fever is released from membranes by a phospholipase?
answer
arachidonic acid is cleaved which is a precursor for eicosanoids
question

Are all signal transduction pathways independent of each other?

 

What do they do or not do to account for this?

answer

No, pathways are independent on each other

 

They inhibit one pathway and pick up slack on other pathway

question
Where does glycolysis take place?
answer
cytosol
question
Starting substrate for glycolysis
answer
glucose
question
Ending products for glycolysis
answer

aerobic - pyruvate

 

anaerobic - lactate

question

What must every cell that metabolizes glucose do first?

 

What enzymes do this?

answer

phosphorylate glucose to glucose-6-phosphate

 

enzyme - hexokinase (in all tissues)

 

or

 

glucokinase (only in liver)

question

Enzyme Substrate and Product for Committed Step of glycolysis?

 

Is ATP generated or used in this reaction?

answer

enzyme - phosphofructokinase-1

 

step is phosphorylation of fructose-6-phosphate to fructose-1,6-bisphosphate

 

ATP is not generated in this step, but is used to transfer Pi to fructose-6-phosphate

question
Control factors that affect glycolysis?
answer

Phosphofructokinase-1 is committed step and heavily regulated by enzymes.

 

IN MUSCLE

 

In muscle, phosphofructokinase-1 is inhibited by citrate and increased levels of ATP.

 

AMP, ADP, cAMP, and Pi reverse the inhibitory affects of ATP on PFK-1.

 

Another control is from the synthesis of pyruvate and ATP from PEP and ADP. In muscle, pyruvate kinase is feedback inhibited by ATP.

 

IN LIVER

 

fructose-1,6-bisphosphatase will remove phosphate from f-1,6-bisphosphate, converting it backwards into fructose-6-phosphate. Phosphatase is also monitored.

 

Fructose-2,6-Phosphate (vasopressin and phenylephrine promote its synthesis) will inhibit this enzyme from removing the phsophate, thus activating PFK-1 when blood glucose is low. Fructose-2,6-Bisphosphate acts as a competitive inhibitor of fructose-1,6-bisphosphatase, inhibiting it from deposphorylating F-1,6-Bisphosphate and increasing the flux of F-6 Phosphate through PFK-1. Glucagon controls F-2,6-bisphosphate, stopping glycolysis and enhancing gluconeogenesis.

 

Another control is from the synthesis of pyruvate and ATP from PEP and ADP. In liver, pyruvate kinase feedback is inhibited by ATP and positively affected by fructose-1,6-bisphosphate.

 

 

 

 

 

 

question
In what steps are ATP generated?
answer

2 steps:

 

1) conversion of 1,3-bisphoshoglycerate by phosphoglycerate kinase, 1 ATP produced.

 

 

2) Second ATP generated by conversion of PEP to pyruvate by pyruvate kinase. A total of 4 ATP (2 net ATP are produced) from glycolysis. 2 ATP are used up during the glycolysis process.

question
What steps of the glycolysis pathway cannot be reversed for use in gluconeogenesis?
answer

3 steps:

 

1) phosphorylation of pyruvate to give phosphoenol pyruvate

 

2) Dephosphorylation of fructose-1,6-bisphosphate to furctose-6-phosphate.

 

3) dephosphorylation of glucose-6-phosphate into glucose.

question
2 types of approaches that are used to get around barriers encountered in reversing glycolytic pathway
answer

gluconeogenesis uses enzymes specific to glucose synthesis

 

Certain processes are localized to certain cellular compartments

question
Subcellular organelles involved in gluconeogenesis
answer

mitochondria

 

ER

question
Malate shuttle and where does it take place?
answer

Mitochondrial matrix.

 

After pyruvate converted to oxaloacetate by pyruvate carboxylase, it must be transported out to cytosol. Mitochondrial membrane doesn't allow oxaloacetate to pass through membrane so it is converted to malate, by malate dehydrogenase.

 

Malate is then transported across membrane to cytosol.

 

Malale dehydrogenase is both in the cytosol and mitochondrial matrix. The cytosolic enzyme converts malate back into oxaloacete.

 

The shuttle also transports NADH as well as oxaloacetate. Mitochondrial malate dehydrogenase uses up mitochondrial NADH for the conversion. The cytosolic malate dehydrogenase will produce NADH in the reverse reaction, replenishing cytosolic NADH.

 

Aspartate Amino Transferase used as an alternative method for transporting oxaloacetate when cytosolic NADH is high.

question
How does glucose-6-phosphate get converted into glucose?
answer

conversion of glucose-6-phosphate occurs in the lumen of the ER.

 

There is a series of transporter proteins that play an integral role in the conversion of glucose.

 

1) T1 translocase pumps G-6-Phosphate into the lumen of the ER. The phosphatase for converting G-6-Phosphate lies in the lumen.

 

2) After dephosphorylation, the dissociated Pi is removed from the lumen into the cytosol by T2 translocase. T2 requires Ca to pump out Pi. A separate channel allows Ca to flow in the ER lumen.

 

3) glucose is pumped out of ER to cytosol by T3 translocase.

 

question
Enzyme used in gluconeogeneis both inside mitochondria and outside cytosol?
answer
malate dehydrogenase
question
Tissues capable of carrying out ALL STEPS of gluconeogenesis?
answer
liver and cortex of kidney
question

Is ATP or NADPH utilized or produced in the petose phosphate pathway?

 

What rxns produce/utilize ATP or NADPH?

answer

PPP does not produce or utilize any ATP, but NADPH (reducing agent) is produced which is why PPP occurs requently is tissues where high amounts of oxidative damage can occur (RBCs and leucocytes) or tissues where lipid or catecholamine synthesis occur also involve PPP for NADPH production (liver, adipose, lactating mammary, adrenal cortex, nervous system. Tissues with high nucleotide synthesis (bone marrow, skin, gastric mucosa) depend on PPP too.

 

NADPH produced in oxidative reactions of G6P and 6-phosphogluconate.

question
What are functions of the pentose phosphate pathway?
answer

1) produce reducing agents, NADPH, for cytosolic rxns

 

2) produce ribulose-5-phosphate for nucleotide synthesis

 

3) provide alternative method for metabolizing glucose

 

4) allow for interconversion of pentoses and hexoses

question
Possible starting materials for pentose phosphate pathway?
answer
glucose-6-phosphate
question
Enzymes , substrate, and product for rate limiting step of pentose phosphate pathway?
answer

Rate limiting step

 

glucose-6-phosphate converted to 6-phosphoglucono-δ-lactone by glucose-6-phosphate dehydrogenase.

 

Glucose-6-dehydrgoenase is inhibited by NADPH and activated by ↑ NADP+ (substrate availability)

question
How can glucose-6-phosphate dehydrogenase deficiency be related to hemolytic anemia?
answer

Reduced glutathione in RBCs react with peroxides to form glutathionedimers. Glutathione can prevent oxidative damage to RBCs. NADPH is used to break up glutathione dimer in the cell and restore glutathione levels to react with other peroxides.

 

A deficiency in glucose-6-phosphate dehydrogenase can't produce enough NADPH to restore glutathione levels.

 

This has 2 effects:

 

1) peroxides build up and damage RBC membranes

 

2) Heinz bodies (cross linkings of Hb) will reduce Hb flexibility, causing rupture of now fragile hemoglobin that is passed through small vesssels.

 

Weakened membranes and Heinz bodies will lead to acute hemolytic anemia, black urine, and increased urine flow (compensation to reduce renal damage from lysed RBCs)

question

In what kinds of tissues is this pathway most active?

 

In what part of the cell is it carried out?

answer

Carried out in tissues with high amts of oxidation such as erythrocytes and leukocytes. Essential is nucleotide synthesis (gastric mucosa, bone marrow, and skin). Frequently occurs in tissues heavily involved in lipid and catecholamine synthesis (adipose, liver, lactating mammary, adrenal cortex, nervous system)

 

Takes place in the cytoplasm.

question
What tissues require ribose phosphate for high rates of nucleotide synthesis?
answer

skin cells

 

bone marrow

 

gastric mucosa

 

generally tissues with a high rate of turnover of cells

question
What tissues require NADPH for lipid and catecholamine synthesis?
answer

liver

 

adrenal cortex

 

lactating mammary

 

adipose

 

nervous system

question
What tissues require NADPH for protection against oxidative damage?
answer

erythrocytes

 

leukocytes

question
What categories of rxns are utilized in the pentose phosphate pathway?
answer

3 categories

 

1) oxidative rxns

 

2) isomerization or epimerization rxns

 

3) rxns that require C-C bonds to be cleaved or formed


 

question
Fatty acid synthesis occurs in what compartment of the cell?
answer
cytosol
question
A hormone that stimulates fatty acid synthesis is?
answer
insulin stimulates fatty acid synthesis in the liver
question
Acetyl CoA carboxylase has a covalently bound prosthetic group called?
answer
biotin
question
Substrates that are required by acetyl CoA carboxylase to form malonyl CoA
answer

ATP

 

bicarbonate

 

acetyl CoA

question
Describe how mitochondrial acetyl CoA is made available in the cytosol
answer

acetyl CoA in mitochondrial matrix combined with OAA to form citrate

 

citrate is transported via a transporter from the mitochondria into the cytosl

 

citrate lyase using CoA cleaves citrate, into OAA and acetyl CoA

 

 

question
Redundant that is required for fatty acid synthesis
answer
NADPH
question
Substrate and products of malic enzyme
answer
malate catalyzed by malic enzyme into pyruvate and CO2
question
vitamin derivative that is part of the ACP portion of the fatty acid synthesis complex?
answer
phosphopantetheine
question
Starting from acetyl CoA and malonyl CoA, describe the steps that are involved in the synthesis of palmitate
answer

1) acetyl CoA + enzyme → acetyl-Enz by acetyl transferase

 

2) malonyl CoA + ACP → Malonyl-ACP by malonyl transferase

 

3) acetyl-enz+malonyl-ACP → acetoacetyl-ACP by keto synthase or condensing enzyme

 

4) acetocetyl-ACP → beta-hydroxybutyryl-ACP by beta-ketoacyl ruductase

 

5) beta-hydroxybutyryl-ACP → crotonyl-ACP by dehydratase

 

6) crotonyl-ACP → butyryl-ACP by enoyl reductase

 

7) butyryl-ACP → palmitoyl-ACP using 6 more malonyl coA in 6 rounds of steps 1-6

 

8) palmitoyl-ACP → palmitic acid by thioesterase

question
name enzyme domain that releases palmitate from the fatty acid synthase complex
answer
thioesterase I domain
question
name the enzyme that is expressed during lactation in mammary glands that is relevant to fatty acid synthesis
answer
thioesterase II
question
Name fatty acids that are released by thioesterase II
answer

capric (C10)

 

lauric (C12)

 

myristic (C14)

 

easier to digest compared to palmitate for sucking infants

question
Name 2 essential fatty acids
answer

linoleic (18:2)(9,12)

 

linolenic (18:3)(9,12,15)

question

All naturally occurring double bonds of fatty acids are of cis configuration?

 

true or false

answer
false (I think)
question
Linoleic acid is the precursor for the biosynthesis of what?
answer
arachidonic acid
question
Storage form of fatty acid
answer
triglycerides
question
Triglycerides are stored in what tissue?
answer
adipose tissue
question
Precursors for the synthesis of triglycerides
answer

fatty acids are acylated by condensing with CoA to form Fatty acyl CoA

 

3 fatty acyl CoAs are then esterified to glycerol-3-phosphate to eventually form triglycerides (also called triacylglycerol)

question
backbone compound on which fatty acids are esterified to form triglycerides are
answer
glycerol phosphate
question
Before beta-oxidation, activated fatty acids are esterified to THIS compound so that it can be transported from cytosol to mitochondria
answer
fatty acyl carnitine
question
Name 3 energy related compounds that are produced upon beta-oxidation of fatty acids
answer

FADH2

 

NADH

 

acetyl CoA

question
Name enzyme in mitochondrial matrix that cleaves fatty acylc carnitine
answer
carnitine acyltransferase II (CPT II)
question
Complete oxidation of stearic acid, myristic acid, and lauric acid, leads to the formation of how many moles of ATP
answer
question
Name a methylated fatty acid that is derived from dairy products
answer
phytanic acid
question
name an enzyme that uses vitamin B12 derivative as a coenzyme in the enzyme catalysis
answer
methyl malonyl CoA mutase
question
Name a 3 carbon compound that is formed from the oxidation of odd chain fatty acid
answer
propionyl CoA
question
Name 2 enzymes that convert propionyl CoA into succinyl CoA
answer

racemase

 

methy malony CoA mutase

question
Name 2 carboxylases that require biotin as a coenzyme
answer

propionyl CoA carboxylase

 

acetyl CoA carboxylase

question
Name a compound that is catabolized by alpha-oxidation
answer
phytanic acid
question
Name an allosteric activator and an inhibitor of acetyl CoA carboxylase?
answer

allosteric activator - citrate

 

inhibitor - fatty acyl CoA

question
Carnitine acyl-transferase is inhibited by what?
answer
malonyl CoA
question
A hormone that triggers catabolism of fats
answer
glucagon
question

Phosphorylation of acetyl CoA carboxylase by protein kinase A inactivates the enzyme

 

True or False?

answer
True
question

Phosphorylation of acetyl CoA carboxylase by hormone sensitive lipase activates the enzyme?

 

True or False?

answer
True
question
Name the defect in Refsum's disease
answer
inability to properly degrade phytanic acid due to deficiency in the alpha hydroxylase enzyme
question
In Sudden Infant Death Syndrome the enzyme that is defective is?
answer
medium chain fatty acyl CoA dehydrogenase deficiency
question
Name 2 conditions that would result in methylmalonic acedemia
answer

methylmalonyl CoA mutase is missing

 

conversion of Vitamin B12 into coenzyme is missing

question
Definition of Obesity
answer
BMI > 30
question
Name a natural and an artificial compound that inhibits fatty acid synthase
answer

natural inhibitor compound - cerulenin

 

artificial inhibitor compound - C75

question
Malonyl CoA inhibits production of a neuropeptide compound called?
answer
NPY
question

Neuropeptide Y signals the inhibition of feeding?

 

True or False?

answer
False
question
Describe diabetic ketoacidosis?
answer

blood concentrations of acetoacetic acid and beta-hydroxybutyric acid are as high as 20 mM.

 

These compounds are strong acids with a pKa of ~3.5, resulting in acidosis

 

In biochemical terms, the events are very similar to starvation mediated ketosis:

 

a) increased glucagon/insulin ratio results in elevation of liver cAMP

 

b) Elevated liver cAMP leads to decreased malonyl CoA

 

c) decreased malonyl CoA leads to de-inhibition of CPT I

 

d) de-inhibition of CPT I results in activation of fatty acid oxidation (fatty acid degradation) and increased ketone body production

 

 

question
Name 2 enzymes that convert alcohol into acetate
answer

alcohol dehydrogenase

 

aldehyde dehydrogenase

question
Name the reductant that is produced during the oxidation of alcohol
answer
NADH
question
How many moles of ATP are produced upon complete oxidation of ethanol?
answer
12 ATP
question
Name a few compounds that are metabolized by omega-oxidation pathway
answer

ω-methyl

 

adjacent methylene carbon of fatty acids

 

fatty acids 6-10 Cs long

question
Upon complete oxidation of capric acid, how many moles of net ATP are produced?
answer

Capric acid = C10 -  4 NADH + 4 FADH2 + 5 Acetyl CoA = (4x3) + (4x2) + (5x12) = 80 ATP

 

question
What are advantages of having fatty acid synthase as a multi enzyme complex as seen in mammals as  opposed to individual polypeptides as seen in bacteria?
answer
more control
question
Why is fat storage energetically better compared to glycogen?
answer

Adipose storage of TAG’s initially uses less energy to produce TAG’s, plus, degradation via ß-oxidation provides

            more energy/ ATP than Glycogen storage

 

question
Explain how ketone bodies can serve as an energy source in brain during starvation?
answer

ketone bodies are synthesized by liver during starvation to feed the brain

 

acetoacetate is converted to acetoacetyl CoA by thiophorase after cross blood brain barrier

 

acetoacetyl CoA can be converted to 2 acetyl CoA by thiokinase

 

2 acetyl CoA then undergo citric acid cycle to produce energy in the brain

question
Why can carnitine palmitoyltransferase I deficiency lead to hypoketosis?
answer

defect in transporting fatty acid carnitine

 

don't have free fatty acids to make acetyl CoA and subsequently don't get ketone bodies

 

don't make enough ketone bodies

question
Why are alcoholics hypoglycemic?
answer
question
What compound is the source of all carbons in cholesterol?
answer
acetyl CoA
question
Cholesterol is the precursor for what 4 major types of compounds?
answer

bile salts

 

vitamin D

 

corticosteroids

 

sex hormones

question
What are the 5 stages in cholesterol biosynthesis that we discussed and their products?
answer

1.)  Mevalonate synthesis → Mevalonate

 

2.) Isoprenoid synthesis → Isoprenoid units

 

3.) Squalene synthesis → Squalene

 

4.)  Lansterol Synthesis → Lansterol


5.)  Synthesis of Cholesterol from Lanosterol → Cholesterol

 

question
What are substrate, enzyme, and product of the rate-limiting step of cholesterol synthesis?
answer

rate limiting step

 

HMG-CoA + 2 NADPH + 2 H+ → Mevalonate + 2 NADP+ + CoASH

question
What are different means by which cholesterol synthesis is controlled naturally?
answer

1.)  Bicyclic control system:

      As insulin ↑ ­, cholesterol ­↑

      As glucagon ↑ ­, cholesterol ↓

 

2.)  HMG-Reductase degradation:

As cholesterol ↑ ­HMG-Reducases downregulates.

 

3.)  Genetic controls:  Sterols and mevalonate metabolites inhibit HMG-Reductase RNA synthesis

 

question
What are the main dietary sources of cholesterol?
answer

meat

 

dairy

 

poultry

question
How does the body get rid of cholesterol?
answer

The body metabolizes some cholesterol into bile salts and steroids.

 

Rest go to tissues for storage or excreted out of body in feces.

question
What are bile salts and their use?
answer

modification of cholesterol by ring hydrozylations and side chain oxidation result is cholic acid

 

cholic acid reacts with amino acids to form amides known as bile salts

 

Fxn: released by gall bladder to help solubilize dietary fats

question
What is the route of circulation for the re-absorption of bile salts?
answer

Liver  → Gall bladder storage Intestine (some to lymphatics)   Bloodstream Liver.

question
What are 2 ways in which pharmaceutical intervention is used to lower patient cholesterol levels?
answer

1) inhibition of HMG-CoA reductase; Mevacor

 

2) in small intestine removal and excretion of bile salts; Colestipol or Cholestyramine

question
What types of compounds supply the precursors for the eicosanoids and where are they found?
answer
glycerophospholipids in plasma membrane
question
What enzyme cleaves the fatty acid off of the starting material?
answer
phospholipase A2
question
What kinds of compounds activate phospholipase A2?
answer

angiotensin

 

bradykinin

 

epinephrine

 

thrombin

question
What kinds of compounds inhibit phospholipase A2?
answer
inhibited by anti-inflammatory corticosteroids through induction of protein inhibitor of phospholipase A2 → lipocortin
question
Where are the general types of eicosanoids and how their names arise?
answer

Eicosanods: Latin for “20” (number of C atoms in the molecules)

 

Prostaglandins:  Thought to be from the prostate gland

 

Thromboxanes:  Isolated from platelets

 

Leukotrienes:  Isolated from leukocytes

 

question
What enzyme  paths are used for the synthesis of prostaglandins, thromboxanes, and leukotrienes?
answer

glycerophospholipid → arachidonic acid

 

cyclooxygenase reaction of arachidonic acid → thromboxane or prostaglandin

 

lipoxygenase reaction of arachidonic acid → leukotriene

question
What compounds inhibit cyclooxygenases?
answer

aspirin

 

non-steroidal anti-inflammatory drugs (NSAIDS)

question
What are some of the effects that prostaglandins can have?
answer

8 EFFECTS

 

stimulate smooth muscle contraction

 

regulate steroid synthesis

 

inhibit gastric secretion

 

inhibit hormone sensitive lipases

 

inhibit platelet aggregation

 

regulate nerve transmissions

 

sensitive to pain

 

mediate inflammatory response

question
What effects do thromboxanes have?
answer
platelet aggregation and vasoconstriction
question
Where are leukotrienes found?
answer

leukocytes

 

mast cells

 

vascular tissue

 

platelets

 

macrophages

question
What pathway is used to synthesize leukotrienes?
answer
leukotrienes are synthesized from arachidonic acid or linolenic acid by the lipoxygenase path
question
What are the slow reacting substances of anaphylaxis?
answer
leukotrienes
question
What biological effects do leukotrienes have?
answer

contraction of smooth muscle in pulmonary airway

 

alteration in permeability of microvasculature, resulting in fluids and proteins leaking into tissues

question
Is the NADH/NAD+ ratio high or low in alcoholics?
answer
high
question
Why does high NADH production in alcoholics lead to lipid formation?
answer

↑ NADH levels indicate excess energy; therefore, ß-oxidation of triacyglycerols doesn't occur resulting in high lipid levels

question
What are ω-3 and ω-6 fatty acids?
answer

ω-3 = Omega-3 Fatty acids = Fatty acids with a double bond 3 carbons away from the last (ω) carbon on the F.A. chain

                   Example = Linolenic acid 18:3 (9,12,15) 


         ω-6 = Omega-6 Fatty acids = Fatty acids with a double bond 6 carbons away from the last (ω) carbon on the F.A. chain

                   Example = Linoleic acid  18:2 (9,12)

 

question
Describe the citrate lyase catalyzed reaction
answer
question
Can carbon skelton from C-17 fatty acid oxidation enter gluconeogenic pathway. If yes, explain how
answer
question
Can a carbon skeleton from C-16 fatty acid oxidation enter the gluconeogenic pathway?
answer
question
Excretion of higher methylmalonic acid through urine is a sign of what vitamin deficiency?
answer
B12?
question
What are the biochemical reasons for the peripheral neuropathy in Vitamin B12 deficient individuals?
answer
lack of vitamin B12 inhibits fat beta oxidation which further has negative effects on myelin synthesis and results in peripheral neuropathy?
question
Describe the pathway of ketogenesis
answer

1) 2 molecules of acetyl CoA → acetoacetyl CoA (thiolase)

 

2) acetoacetyl CoA → HMG CoA

(HMG CoA synthase)

 

3) HMG CoA → Acetoacetate + Acetyl CoA

(HMG CoA lyase)

 

4a) Acetoacetate → Acetone

(Spontaneous)

 

or

 

4b) Acetoacetate → Beta-Hydroxy Butyrate

(dehydrogenase)

 

 

question
Describe the pathway of ketogenolysis
answer

Ketogenesis occurs before

 

Acetoacetate

 

1) Acetoacetate → Goes Through Blood to Tissue

 

2) Acetoacetate + succinyl CoA → Acetoacetyl CoA

(thiophorase)

 

3) Acetoacetyl CoA → 2 Acetyl CoA

(thiokinase + CoA)

 

4) 2 Acetyl CoA enter TCA cycle to produce energy

 

SEE PAGE 67

question
Can muscle use ketone bodies as energy source? If yes, explain how ketone bodies enter energy metabolism?
answer

Yes, muscles can use ketone bodies as energy source

 

2) Acetoacetate + succinyl CoA → Acetoacetyl CoA

(thiophorase)

 

3) Acetoacetyl CoA → 2 Acetyl CoA

(thiokinase + CoA)

 

4) 2 Acetyl CoA enter TCA cycle to produce energy

 

question
Explain the hormonal bases of ketogenesis (in liver) and ketogenolysis (in extrahepatic tissues) in Type I diabetes?
answer

Insulin production = [Glucagon]/[Insulin] ratio, hence, F.A.’s will be mobilized via Hormone sensitive Lipase. 

 

Due to  Insulin, there will be an increase in F.A. ß-oxidation producing an overabundance of Acetyl CoA, which is then converted into Ketone Bodies.  The [Ketone Body] , and because these compounds contain highly acidic protons (pKa = 3.5), the blood pH will become acidic = DKA.

question
High NADH/NAD+ in alcoholics results in the production of what?
answer
3-hydroxybutyrate (beta-hydroxybutyrate)
question
A person with a deficiency of vitamin B12 is recommended to avoid what type of food?
answer
fatty food ???
question
A person with biotin deficiency cannot metabolize what fatty acid?
answer
question
Name 3 types of sphinogolipids and describe them
answer

sphinogomyelin

 

impt membrane component esp. in nervous sytem

synthesized from 2 routes by ceramide


ceramide

 

immediate precursor of sphinogolipids

second messenger for NGF

 

globoside

 

neutral cerebroside oligosaccharides

 

gangliosides

 

acidic ceramide oligosaccharides that contain N-acetyl neuraminic acid (NANA or sialic acid)

question
What compounds are the precursors for sphinogosine?
answer
serine and palmitoyl CoA
question

How is ceramide formed?

 

answer

Sphingosine + acyl CoA  Ceramide + CoASH

                                       (Acyl CoA transferase)

 

question
How is sphingomyelin synthesized?
answer

ceramide + CDP-choline → sphingomyelin + CMP

 

OR

 

ceramide + phosphatidyl choline → sphingomyelin + DAG

question
What are the 4 types of glycosphinogolipids?
answer

cerebrosides

 

sulfatides

 

globosides

 

gangliosides

question
How are cerebrosides synthesized?
answer
ceramide + UDP sugar → cerebroside + UDP
question
What is PAPS and what is it used for?
answer

3’-phosphoadenosine-5’-phosphosulfate

 

It is an activated sulfate which converts galactocerebroside to sulfatide

 

question
What defect exists in Gaucher's disease?
answer
Deficiency of glucocerebrosidase, preventing degradative path of Glucocerebroside to Ceramide.  This is the most common sphingolipidoses (lipid storage disease)
question
What defect exists in Tay-Sachs disease?
answer
deficiency of hexoaminidase A
question
What are the structural features of gangliosides?
answer
acidic ceramide oligosaccharides that contain N-acetyl neuraminic acid (NANA or sialic acid)
question
What does semiconservative replication mean?
answer
the 2 daughter double-stranded DNA molecules each contain 1 strand of parent DNA
question
What 3 observations have been made for all DNA polymerases?
answer

Incoming base paring is selected by complementary base pairing with a template strand.

 

Chain growth is in the 5’ to 3’ direction

 

All DNA polymerases require a primer strand to add bases to.

 

question
What is the function of DNA polymerase I?
answer

prokaryotic DNA elongation and repair

 

5'-3' polymerization activity (synthesis)

 

5'-3' exonuclease activity (repair and removal)

 

3'-5' activity (proofreading)

question
What is the Klenow fragment?
answer
larger subunit of DNA polymerase I that contains 5'-3' synthesis activity and 3'-5' proofreading activity
question
What is the function of DNA polymerase III?
answer

prokaryotic DNA elongation and repair enzyme

 

complex structure; 10 subunits

 

forms a sliding clamp on the DNA strand

 

has a higher processivity than DNA polymerase I

question
What is the function of a topoisomerase?
answer

enzyme that changes the topography of DNA molecules by cutting strands; allows the amount of supercoiling to be adjusted and re-ligating the strands

 

relieves supercoiling

question
What is the function of a helicase?
answer
enzyme that catalyzes the unwinding of double stranded DNA by disrupting base-pair H-bonding
question
In replication, what is the leading strand and what is the lagging strand?
answer

leading strand - DNA continuously synthesized in 5'-3' direction

 

lagging strand - DNA discontinuously synthesized in 3'-5' direction (Okazaki fragments)

question
How is RNA used in DNA replication?
answer
RNA sequences serve as the primer sequences for DNA polymerase in the discontinuous synthesis of the lagging strand
question
What are Okazaki fragments?
answer

pieces of DNA that are replicated on the 3’-5’ (lagging) strand that will eventually be joined by ligases to make a complete DNA replicate strand.

 

question
Where is E. coli DNA replication initiated and where is it terminated?
answer

initiated at oriC

 

terminated at the tau or ter site

question
What are the processivities of DNA polymerases I and III?
answer

DNA polymerase I has a low processivity (20 bases before it disassociates)

 

DNA polymerase III has a high processivity (5 million bases before it dissociates)

 

 

 

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Where is DNA found in eukaryotes?
answer
in the nucleus
question
How is DNA packaged in eukaryotes?
answer
the double stranded DNA moleculed are wrapped with their negatively charged phosphate groups around octamers of positively charged proteins called histones
question
What are some contrasts between features of prokaryotic and eukaryotic DNA replication?
answer

Eukaryotic DNA is much longer, the synthesis is much slower and occurs in accordance with the cell cycle.

 

Eukaryotic cells use a large number of DNA polymerase molecules and begin replication at multiple sites.

 

question
What DNA polymerase is believed to be responsible for leading strand synthesis and which for lagging strand synthesis in eukaryotes?
answer

leading strand synthesis - DNA polymerase delta

 

lagging strand synthesis - DNA polymerase alpha

question
What proteins are in nucleosomes and why do they bind to DNA?
answer

nucleosomes contain positively charged histone proteins

 

these + charged histones are attracted to the - charged  phosphate groups of DNA

question
What is PCNA and what role does it play?
answer

Proliferating cell Nuclear Antigen (PCNA) is a cyclin that forms a clamp around the template DNA strand to dramatically increase the processivity of DNA polymerase delta.

 

question
What is the arrangement of nucleosomes after DNA replication?
answer

Nucleosomes are cooperatively distributed after DNA replication

 

The new histones end up along one daughter stand near each replication fork

 

The histones from the original nucleosomes are found in the nucleosomes reformed along the other new strand

 

question
How might nucleosomes affect eukaryotic DNA replication?
answer

The presence of these histones (specifically the original ones, that remain associated with one strand of the replication fork) (may be why DNA polymerization is so much slower in eukaryotes)

 

question
What is the model used to describe DNA replication in mitochondria?
answer
displacement loop replication
question
What are the overall anabolic and catabolic pathways involved in nucleotide metabolism?
answer

anabolic - purine and pyrimidine de novo synthesis and salvage pathways

 

 

catabolic - purine and pyrimidine degradation pathways

question
What major difference is there between purine and pyrimidine synthesis in terms of when and how the ring is added?
answer

purines - the ring is built as the pathway progresses.

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pyrimidines, the ring is built 1st, then added to the PRPP.

 

question
Both purine and pyrimidine synthesis have a molecule in common. What is that molecule?
answer
PRPP
question
What molecule is used at the start of the purine synthesis pathway?
answer
PRPP
question
What molecule is formed by the purine synthesis pathway?
answer
IMP
question
What is the name of the enzyme that catalyzes the addition of the first component of the purine ring?
answer
PRPP synthetase
question
What nitrogen-containing amino acid donates this first part of the ring?
answer
glutamine
question
How many enzymatic steps are required to synthesize IMP from PRPP in humans?
answer
10 steps
question
What is the cellular localization of all the enzymes that carry out these steps (many of the steps are carried out by enzymatic activities contained on a single polypeptide chain).
answer
the cytosol
question
What carrier is utilized in two different steps to add to the ring?
answer
N10 formyl tetrahydrofolate
question
What vitamin is N10 formyl THF derived from?
answer
folate
question
What atom does N10 formyl THF donate? Hint- the class of enzymes known as transformylases catalyze these steps.
answer
C atom
question
What are glial cells?
answer
supporting neuronal cells that maintain the normal physiology of the nervous system
question
What are some of the biochemical functions of microglia, astrocytes, and oligodendocytes?
answer

MICROGLIA

 

fight infections; release inflammatory substances that could damage neurons

 

ASTROCYTES

 

regulate molecules necessary for inter-neuron communication

 

clear glutamate in the synapse to stop the neurotransmission mediated by glutamate

 

release neural growth factors

 

take up monoamine transmitters like serotonin or dopamine

 

OLIGODENDROCYTES

 

provide fatty myelin sheaths that insulate axons in the CNS

 

multiple sclerosis results when axonal connections die off

 

question
Acetycholine is not metabolized by reuptake process. Explain which cells would catabolize acetylcholine after action potential?
answer
astrocytes
question
Explain the differences between endogenous proteolysis (protein degradation) VS digestion related protein degradation.
answer
question
What are normal blood creatinine values?
answer
< 1.5 mg/dl
question
Describe the metabolism of glucogenic and ketogenic amino acids in relation to TCA cycle.
answer

different amino acids (both ketogenic and glucogenic) synthesize different components of the TCA cycle.

 

For example, both aspartate and asparagine synthesize oxaloacetate

 

SEE PG. 71 IN DR. VENK'S LECTURE #1

question
Describe the lactate dehydrogenase catalyzed reaction.
answer

(1) pyruvate→lactate (LDH M)

 

(2) lactate→pyruvate (LDH L)

 

Prolonged muscle activity results in pyruvate being converted into lactate by LDH M

 

lactate then moves from the muscle into blood and enters the liver

 

In the liver, LDH L converts lactate back into pyruvate

 

pyruvate is further metabolized to form glucose to gluconeogenesis

 

This entire process is known as Cori's cycle.

question
When lactate accumulates in the blood it is a problem. Why?
answer

accumulation of lactate in the blood leads to lactate acidosis

 

indicative of tissue hypoxia, hypoperfusion, and possible damage

question
Describe the catecholamine synthesis pathway.
answer

(1) tyrosine→DOPA (tyrosine hydroxylase)

 

(2) DOPA→dopamine (DOPA decarboxylase)

 

(3) dopamine→norepinephrine (hydroxylase)

 

(4) norepinephrine→epinephrine

(methyl transferase)

 

Rate limiting step = tyrosine hydroxylase catalyzed reaction (step 1)

 

Step 1 requires molecular oxygen and tetrahydrobiopterin (THB)

 

question
Explain why vitamin B6 deficiency can cause brain related problem.
answer

GABA is found in high concentrations in the brain where it serves as an inhibitory neurotransmitter.

 

glutamate→GABA (glutamate decarboxylase)

 

The enzyme requires the vitamin B6 derivate pyridoxal phosphate as a coenzyme so deficieny of vitamin B6 would impair activity of the decarboxylase and production of GABA.

question
Describe the biosynthesis of serotonin and melatonin.
answer

Synthesis of Serotonin

 

1) Tryptophan→5-hydroxy tryptophan

(tryptophan hydroxylase)

 

2) 5-hydroxy tryptophan→serotonin

(decarboxylase)

 

Synthesis of Melatonin

 

1) serotonin→N-acetyl serotonin

(NAT)

 

2) N-acetyl serotonin→melatonin

(methyl transferase)

 

 

question
Describe the biosynthesis of histamine and its functions.
answer

histidine→histamine

(histidine decarboxylase)

 

Functions: 1) mediate allergic and inflammatory reactions

 

2) powerful vasodilator

 

3) causes constriction of bronchioles in lungs

 

4) stimulates secretion of HCl in stomach

question
Describe the biosynthesis of creatine phosphate and its degradation.
answer

Synthesis

 

1) arginine + glycine→guanido acetate + ornithine

(transamidase)

 

2) guanidino acetate→creatine

(SAM-dependent methylation)

 

3) creatine→creatine phosphate

(creatine kinase)

 

Degradation

 

1) phosphocreatine→creatinine

(non-enzymatic conversion)

 

creatinine is excreted through the urine

question
Which vitamin derivative is required as a cofactor for many of the decarboxylases?
answer

pyridoxal phosphate

 

derived from vitamin B6

question
Describe the three nitric oxide synthases and the respective functions of the nitric oxides in different tissues.
answer

Endothelium-derived NO

 

NO diffuses out of endothelial cells and into vascular smooth muscle cells.

 

Activates cytosolic guanylate cyclase→increases cGMP

 

Activation of cGMP dependent protein kinase→phosphorylation of smooth muscle contractile proteins and relaxation

 

Brain-derived NO

 

receptors for NO in neurons

 

stimulation of guanylate cyclase→increased cGMP synthesis

 

Proteins that are phosphorylated and activated not well understood

 

Macrophage-derived NO

 

due to infections by bacteria, NO synthesis stimulated

 

NO toxic to bacteria

question
Biochemical basis for Parkinson's
answer

degeneration of the substantia nigra leads to reduced dopamine production

 

treated by: administration of L-DOPA which is precursor of dopamine that can cross blood brain barrier

question
Biochemical basis for depression
answer

Serotonin from synaptic cleft is taken up by presynaptic cells for catabolism

 

Treated with: Prozac which inhibits the serotonin reuptake process and enables prolonged serotonin presence in synaptic cleft

question
Biochemical basis of pheochromocytomas
answer

tumors of chromaffin tissue that produce large amounts of catecholamines

 

leads to hypertension

question
Biochemical basis of Huntington's
answer
Now thought to be a polyglutamine trinucleotide repeat problem rather than a problem with low GABA levels
question
What is the definition of biopharmaceutical? What is the definition of recombinant DNA?
answer

biopharmaceutical - drug produced in living cells

 

recombinant DNA - taking a given DNA sequence and putting it together in a different arrangment

question
Describe how one "recombines" DNA including cutting, hybridizing, and ligating it. What enzymes are utilized for cutting DNA?
answer

cutting - use restriction enzymes

 

hybridizing - complementary base pairing of strands in test tube; GC and AT pairs (H bonds)

 

ligation - covalent bonds btwn base in each strand; ligases make covalent bonds; permanently put DNA strand back together; make sequence functional

 

 

question
What is a plasmid? Give an example of a gene found on a plasmid that is naturally occurring.
answer

small DNA circle in bacteria that can be cut with restriction enzymes and recombinant DNA can be replicated by ligating the recombinant sequence into the bacterial chromosome and allowing the bacteria to produce many copies of the DNA sequence

 

gene on a plasmid that is naturally occurring - Bacillacis anthracis toxins in DNA

question
What about insulin causes difficulty in producing it be recombinant DNA means (2 things)?
answer

not 1 polypeptide chain but 2 (A and B chains)

 

3 disulfide linkages and bacteria don't have disulfide linkages

question
What are the advantages of producing insulin in bacteria?
answer

bacteria produces more product than yeast

 

bacteria easier to set up and maintain than yeast

question
What are the advantages of producing insulin in yeast?
answer

insulin is already folded and disulfide bonds are linked correctly

 

more like mammalian cells

question
What do we mean by calling Enbrel (etanercept) a fusion protein? Why does it involve fusing 2 proteins, i.e. what properties are due to each part? What do we mean by calling Enbrel a decoy?
answer

block TNF alpha signal transduction pathway

 

fusion protein b/c it binds to the TNF alpha receptor with a receptor domain and a immunogammaglobulin to pull TNF alpha away from cell and float in circulation (decoy)

 

 

question
It might be quicker to go from the idea of inhibiting TNF to a drug by making the drug as a biopharmaceutical than it would be to go from the idea of making a conventional drug. Why? What might be an advantage of a small molecule conventional drug?
answer

it can take a lot of time in the lab to grow small molecule drugs and see what blocks signal transduction pathway

 

This small molecule conventional drug might have a more specific effect???

question
What are the advantages of producing Enbrel in Chinese Hamster Ovary cells?
answer

folding is more like a human than yeast

 

additions of sugars and other modifications are required for some proteins that can be done by the hamster ovary cells

question
Are drugs on the market more likely to be polyclonal antibodies, or are they more likely to be monoclonal antibodies, or are they more likely to be recombinant DNA molecules based on monoclonal antibody sequence information? Why? What is meant be humanized antibody?
answer

recombinant DNA molecule based on moloclonal antibody sequence information b/c eliminate human immune response to mouse antibody

 

humanized antibody - monoclonal antibody exposed to  humans and those humans who don't have an immune response have their DNA substituted for the mouse DNA to prevent an immune reaction

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