Medical Biochemistry I-Exam 1 – Flashcards
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Unlock answersWhat stabilizes higher order structures in proteins? |
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Amino Acids that are likely to carry charges on side chains at neutral pH |
aspartic acid, glutamic acid, tyrosine, cysteine have negative charges
lysine, arginine, and histidine have positive charges |
Zinc fingers, kringle domains, and leucine zippers are |
Zinc fingers
loop of 23 AA resulting from Zn ion being complexed to 4 AA, usually cysteines and histidines
Kringle domains
conserves seq that fold into large loops that are stabilized by 3 disulfide linkages. Impt in protein-protein interactions with blood coag factors.
Leucine Zippers
arrangments of leucines along one side of an alpha-helix btwn 2 proteins, so that protein can form dimers leaving basic AA regions to bind DNA |
Ways Proteins Can Be Denatured
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Hydrophobic Effect |
when hydrophobic regions of protein in tertiary structure are moved inward and hydrophilic regions outward |
In which human organ is myoglobin (Mb) most impt? |
heart b/c rapid O2 supply needed |
Explain causes and importance of right shift in Hb/O2 binding curve |
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 |
In Hb, how does binding of first oxygen molecule affect binding of next ones? |
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
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What is Bohr effect? |
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 |
Physiological importance of cooperativity in Hb function |
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 |
Compare behavior of Mb and Hb with respect to O2, CO2, and H+ |
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) |
How does protein (globin) portion of Mb or Hb affect reactivity of heme? |
weaken strength of heme-O2 interaction. Heme binds O2 so strongly it 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 |
How and where does 2,3-BPG interact with Hb? |
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 (increase O2 release) |
Where does 2,3-BPG come from? |
product of glycolytic pathway |
How does fetal Hb (HbF) differ from HbA? |
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 ; ; |
What does Hill Eqn describe? |
importance of cooperativity |
How does NO interact w/ Hb and what is physiological significance of that interaction? |
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 |
What is difference btwn HbS and HbA? |
HbA has normal beta chain while HbS has sickle 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 |
Physiochemical/Pathological Basis for All Clinical Manifestations of Sickle Cell Disease |
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 |
How is Sickle Cell Disease Inherited? |
recessive disorder. Only homozygous HbS cause the disease to become expressed. |
What is an enzyme? |
a protein catalyst for specific biochem rxns. ; It will not undergo chem rxn itself and can be reused for other rxns |
What does enzyme effect and not effect in rxn? ; ; |
Enzymes reduce activation energy. ; Keq and delta G are not affected by enzymes. |
Name and describe 2 models used to describe enzyme specificity and/or catalytic activity |
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 |
What is prosthetic group? |
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 |
Name 6 Classes of Enzymes |
oxidoreductases-catalyze RED/OX reactions Ex-H+ donor to substrate transferases-transfer group from one molecule to another Ex-phosphorylases 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 |
What is Michaelis-Menton Eqn and what do terms mean? |
V = Vmax[S]/(Km+[S]) ; V - velocity of rxn Vmax - max rxn velocity [S] - substrate concentration Km - constant value for a specific substrate ; |
In a Michaelis-Menton plot, where is Vmax and how do you find Km? |
Vmax - when [S] is very high ; Km - [S] when V = 1/2(Vmax) |
A Lineweaver-Burk plot is also called a --------- |
Double-reciprocal plot |
What is plotted on Lineweaker-Burk plot and what are the x- and y-intercepts of the plot? |
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 |
What are advantages of the Eadie-Hofstee plot? |
The E-H plot gives more evenly spaced data points than the L-B plot. |
What characteristics distinguish a competitive inhibitor from the other types of inhibitors? |
bind directly to the active site and can be overcome by increased [substrate].
Other inhibitors bind to other sites on enzyme |
On the Lineweaver-Burk plots are the vertical or horizontal intercepts the same or different for competitively inhibited rxns? |
same y-intercept
different x-intercepts |
On the Lineweaver-Burk plots are the vertical or horizontal intercepts the same or different for non-competitively inhibited rxns? |
different y-intercepts
same x-intercepts |
On the Lineweaver-Burk plots are the vertical or horizontal intercepts the same or different for uncompetitively inhibited rxns? |
different y-intercepts
different x-intercepts |
What does inhibitor react with for competitive inhibition? |
active site of the enzyme |
What does inhibitor react with for non-competitive inhibition? |
react with enzyme to reduce its effectiveness to bind w/ substrate |
What does inhibitor react with for uncompetitive inhibition? |
bind with ES complex.
irreversible inhibitors. |
Sigmoid V versus [S] plot and curved Lineweaver-Burk plots indicate |
allostery and positive cooperativity of the enzyme (n = 2) |
What factors determine the amount of enzyme activity in serum? |
amount of tissue producing enzyme
rate of enzyme released
rate of enzyme inactivation/elimination from plasma |
Define: Standard International Unit (SIU) |
1 standard international unit of enzyme activity converts 1 μM of substrate/minute |
2 most commonly measured serum aminotransferases and describe rxns they catalyze |
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 |
In which pathological states are the two most commonly measured serum aminotransferases elevated? |
AST - liver damage and myocardial cells,hemolysed blood
ALT - liver damage |
Reaction catalyzed by γ-glutamyltranspeptidase and how it is used diagnostically? |
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
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2 commonly measured phosphatases and how are they used diagnostically? |
Alkaline phosphatase (ALP)
Hydrolyzes 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
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Diagnostic utility of LDH |
Used to detect MI and hemolysis |
"flipped" LDH |
Most common form is LDH2 (HHHM)
After MI or hemolysis, LDH1 (HHHH) predominates causing a "flipped" LDH b/c LDH1>LDH2 |
What reaction does LDH catalyze? |
Lactate + NAD → pyruvate + NADH + H
interconversion of pyruvate and lactate |
Another name for alpha hydroxybutyrate dehydrogenase (HBD)?
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LDH1 |
What does elevated serum HBD mean? |
damage to myocardial cells due to recent MI |
Reaction catalyzed by CK (CPK) |
creatine phosphate + ADP → Creatine + ATP |
Diagnostic meaning of elevated serum CK |
has 2 subunits, M and B
MB-MI or brief ischemia
MM-vigorous exercise, injection, convulsions
BB-neural tissue damage |
Diagnostic significance of elevated serum amylase |
pancreatitis
morphine |
Reaction catalyzed by serum amylase |
starch + H2O → maltose, maltotriose & limit dextrins
digest starch |
Elevated serum lipase means |
pancreatic pathology
morphine |
Reaction catalyzed by serum lipase |
trigylceride + H2O → fatty acids + glycerol
fat digestion |
What are troponins and how are they used in diagnosis? |
proteins that function in the contractile apparatus of the muscle
Cardiac troponin I is increased in plasma 3-6 hours after MI |
Serum Enzyme Levels in crush injury |
mildly elevated alkaline phosphatase (healing bone)
elevated creatine kinase MM (skeletal muscle) |
Serum Enzyme Levels in vigorous exercise |
elevated creatine kinase MM (skeletal muscle) |
Serum Enzyme levels in morphine injection |
elevation of serum amylase and lipase |
Serum Enzyme Levels in pregnancy |
mildly elevated alkaline phosphatase (bone growth)
elevated GGT |
Four Categories of Cell Adhesion Molecules |
integrins
immunoglobulin superfamily
cadherins
selectins |
Which of the CAM categories would be actively involved in transmitting signals from the inside to the outisde of the cells and vice versa? |
integrins |
What CAM category is involved in adherens junction between cell? |
cadherins |
Abbreviations for 3 types of adhesion molecules of Ig suberfamily and tell their origins |
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 |
4 Diseases in which CAMS are involved |
Rheumatoid arthritis - overexpression of VCAMs
Psoriasis - form of an integrin
Pemphigus vulgaris - autoantibodies interacting with desmoglein
von Willebrand disease - expression of P-selectin |
Describe alpha-helix |
tightly coiled, stabilized by H bonding btwn imido groups and oxygen of carbony groups, many helices (3.6 AA/turn) |
Beta sheet |
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 |
Beta turns |
H bonding of AA 3 sequences apart in same chain
results in U turn bend of chain |
What AA usually phosphoylated in proteins? |
ser
thr
tyr |
Commonly occurring modification of AA found in some proteins |
acetylation of N terminus
carboxylation - add COOH
hydroylation - add OH
glycosylation - add glucose
phosphorylation - add phosphate group
disulfide linkages |
Primary Structure |
AA sequence |
Secondary Structure |
alpha helix
beta-pleated sheets
beta-turns
random coiling
results from free roation of bonds besides peptide bonds |
Tertiary Structure |
secondary structures fold on each other
hydrophobic - inside hydrophilic - outside |
Quarternary Structure |
multiple polypeptide chains interact by noncovalent bonds to form single structure |
General Solubility Prop. of Proteins |
fibrous and insoluble
globular and soluble
firbrous and soluble |
Functions of Proteins |
structural roles
enzymes
role in contractile structures
transport (Hb)
hormones
receptors
Abs |
What are proteins and peptides made of? |
peptides - moderate chain length polymers of amino acids joined by peptide bonds
proteins - polymeric compounds composed of AA joined by peptide bonds |
What is unique about peptide bond? |
it is rigid b/c tautomerism |
In ABO blood group, where is difference in oligosaccharide located and how sugars different? |
due to presence or absence of N-acetyl-galactosamine or galactose linked to penultimate galactose by C1-C3 linkage
1 sugar difference |
Glycosaminoglycans and 2 Ex |
unbranched polysacc w/ repeating disacc - one is AA, other is uronic acid
Ex - hyaluronic acid and heparin |
3 Impt Disacc and which alpha or beta linked? |
maltose - alpha linked
sucrose - alpha linked
lactose - beta linked |
3 Most Impt polysacc and what are linkages? Why is linkage impt? |
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 |
What is glycoside? |
anomeric -OH group of sugar reacts w/ another -OH compound
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aglycone |
compound that attaches to anomeric C of sugar |
Name and describe 2 commonly found mod. of sugars |
amino sugar - -OH group replaced by amino group Ex - glucosamine, galactosamine
deoxy sugar - 1 OH group replaced by H Ex - 2-deoxyribose |
2 conformation of 6-membered rings |
boat and chair |
What is mutarotation and where does it take place? |
configuration changes in molecule by ring opening and closing
occurs at anomeric C |
Pyran and furan are named after which sugar structures and how many Cs are in each? |
pyranose - 6 C ring
furanose - 5 C ring |
Most Impt Monosacc and Polysacc made up of this monosacc |
glucose - most impt monosacc
Polysacc made up of glucose - starch cellulose glycogen |
What are aldoses? |
monosaccharides w/ aldehyde group |
What are ketoses? |
monosaccharides w/ ketone group |
What are carbohydrates? |
polyhydroxy aldehydes or ketones or compounts that can by hydrolyzed to these |
Two Ex of Differences Between Identical Twins that Illustrate that Environment plays a role in development and health |
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 |
What percentage of live births suffer from a disease causing monogenic defect?
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1/100 or 1% of libe births suffer from a monogenic defect |
What percentage of live births suffer from a disease-causing chromosomal abnormality? |
1/1000 or 0.1% of live births suffer from a disease-causing chromosomal abnormality |
How many of the chromosomes are X chromosomes? |
normal female - 2 X chromosomes
normal male - 1 X chromosome |
How many chromosomes are Y chromosomes? |
normal female - 0 Y chromosomes
normal male - 1 Y chromosome |
How many of the chromosomes are considered autosomes? |
44 (22 from father, 22 from mother) |
What is an autosome? |
a chromosome that is not a sex chromosome |
4 trisomies for which live birth are possible |
trisomy 13
trisomy 18
trisomy 21
trisomy X
XYY |
Which of the 4 trisomies produces mild to undetectable symptoms? |
trisomy XYY
trisomy XXX |
Which trisomy is otherwise known as Down's syndrome? |
trisomy 21 |
What is XYY syndrome? |
tall
other mild symptoms |
What is Klinefelter's Syndrome? |
male
testicular failure
can't conceive |
What is Turner's Syndrome? |
X-
sexually immature
short
web neck
phenotypically female |
How does x-linked disease inheritance differ from inheritance of an autosomal disease? |
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 |
How does inheritance of a mitochondrial disease differ from the inheritance of an autosomal disease? |
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 |
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
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B. parents both heterozygous for a dominant disease will have greatest # of offspring |
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
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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) |
Explain how penetrance might mean that individuals with disease symptoms might not be observed in a pedigree |
Just because genotypically the person has the disease doesn't mean they express it phenotypically |
Genotype?
Phenotype? |
genotype-genetic makeup
phenotype-physical manifestation |
How does penetrance affect onset of hereditary hemochromatosis? |
used to be thought rare
now known as the most common hereditary disease in the USA |
What environmental factors affect the onset of hereditary hemochromatosis? |
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 |
Why does an X-linked disease such as Duchenne muscular dystrophy seldom cause symptoms in females? |
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 |
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? |
imprinted |
Which is meant by "a genetic disease is never inherited"? |
A defect that if inherited would prevent the survival of the fetus and/or prevent reproduction of the fetus |
What disease is a genetic disease in which the mutations that cause it often occur after birth? |
cancer |
Tay Sachs inheritance type |
autosomal recessive |
cystic fibrosis inheritance type |
autosomal recessive |
sickle cell anemia inheritance type |
autosomal recessive |
Huntington disease inheritance type |
autosomal dominant |
hereditary hemochromatosis type of inheritance |
autosomal recessive |
Duchenne muscular dystropy inheritannce type |
x-linked (recessive) |
familial hypercholesterolemia inheritance type |
autosomal dominant |
Leber's hereditary optic neutopathy type of inheritance |
mitochondrial |
genetic defect in Huntington disease |
a triplet repeat of CAG (glutamines) amino acids that encode for polyglutamine tract.
Normally - ≤ 34
Have Disease - ≥ 37 |
most common inherited disease in the USA |
hereditary hemochromatosis |
Is hereditary hemochromatosis fatal w/o txt? |
yes |
most common lethal inherited disease |
cystic fibrosis |
What protein in defective in cystic fibrosis? |
CFTR (Cl- transporter) |
Is what organ is the defect of cystic fibrosis most problematic? |
lungs |
What problem generally causes death in cystic fibrosis? |
lung infections caused by P. aeroginosa
accumulates in lungs and destroys lining |
What does the protein involved in cystic fibrosis do to promote the eventually fatal action that happens? |
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) |
2 inherited diseases that protect against infectious disease and what they protect against |
cystic fibrosis - protect from typhoid fever
sickle cell anemia - protects from malaria |
Enzyme defective in Tay Sachs disease |
hexosaminidase A |
What builds up and where does it build up in Tay Sachs? |
glycosphinogolipids build up in the brain |
What are the symptoms of Tay Sachs? |
mental retardation
blindness
paralysis
muscle atrophy
cherry red spot on retina |
Is hexosaminidase A the only enzyme that is involved in trimming sugars off glycosphinolipids that is defective in disease? |
no |
What is class of diseases that involve defective enzymes involved in trimming sugars off of glycosphingolipids? |
sphinogolipid storage disorders |
3 monogenic or polygenic diseases |
hypertension
cardiovascular disease
type 2 diabetes |
Only polygenic diseases |
anencephaly
spina bifida
cleft lip/palate
alchoholism
asthma
bipolar disorder
inherited epilepsy
idiopathic gout
obesity
schizophrenizia
type I diabetes |
3 inherited monogenic diseases that cause hypertension |
glucocorticoid-remediable aldosteronism
apparent mineralocorticoid excess
Liddle syndrome |
polygenic syndrome that is generally considered cause of most hypertension |
essential hypertension |
3 genes that have been associated with type 1 diabetes |
3 HLA genes |
Name genes that have been associated with a monogenic disease that may be though of as type 2 diabetes |
MODY 1-7 |
3 genes that have been associated with polygenic type 2 diabetes |
PPAR-gamma
glucokinase
calpain 10 |
Are all individuals with a defect in one of the genes associated with polygenic type 2 diabetes going to develop the disease? |
no |
Which of these genes associated with type 2 diabetes has been found in 85% of the world population? |
PPAR-gamma |
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 |
anthrax
leprosy |
What is a "snip" and with what frequency are SNPs encountered in human DNA? |
single nucleotide polymorphisms
1:300 bps |
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? |
some people have an intermediate number of repeats (mid-30s) but for someone with 20 repeats the test is certain. |
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? |
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
|
autosomal recessive homozygote
male and female
which get disease? |
female and male |
autosomal recessive heterozygote
male and female
which get disease? |
neither |
autosomal dominant homozygote
male and female
which get disease? |
both |
autosomal dominant heterozygote
male and female
which get disease? |
both |
x-linked recessive hemizygous |
male
|
x-linked recessive heterozygote
male and female
which get disease? |
neither |
x-linked recessive homozygote
male and female
which get disease? |
female |
Mitochondrial, only father has disease
male and female
which get disease? |
neither |
Mitochondrial, only mother has disease
male and female
which get disease? |
Both |
What are some ways DNA is obtained from children and adults? |
blood
saliva
cheek swabs |
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? |
chorionic villus sampling (CVS) - 0.5-1.0% loss
ultrasound - 0% loss
cordocentesis- 1-2% loss |
What does preimplantation diagnosis of in vitro eggs allow? |
embryo selection |
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? |
35 diseases screened in FL
cause early damage and effective txt exists
tandem mass spectrometry-analyzes metabolites |
Advantages of screening for genetic diseases by DNA sequencing |
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) |
Disadvantages of screening by DNA sequencing |
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 |
% frequency of two most often occuring mutations in CTFR genes
Any high frequency mutations in familial hypercholesterimia genes? |
70% and 2.5%
no, high freq mutations in FH genes |
Gene defect that resulted in fava beans causing health problems in Greece and primaquine causing health problems in WW2 |
hemolytic anemia |
Knowledge of person's VKORC1 and CYP2C9 seq can help you decide what about a patient?
What other seq can be screened? |
drug dosage and type
P450 screened also
|
Pharmacogenomics |
use sequence info to make decisions about a drug |
A 27 y/o patient's father has been diagnosed with Huntington disease. It would be important to: |
tell the patient there is a test involving DNA seq to show if he will suffer from Huntington disease later in life |
Is Cushing syndrome characterized as a cancer b/c it involves overgrowth of cells (a tumor) in the adrenal gland that produces cortisol? |
No, it is not metastatic |
What can be involved in genesis of cancer and which always involved? |
bacteria
viruses
inherited predispositions
gene defects - always involved
enviro causes
|
cell cycle genes |
Rb and p53 |
growth signal transduction genes |
ras, HER2, PDGF, EGF |
DNA repair genes |
hMLH1
hMSH2 |
BRCA-1 |
anti-oncogene |
Why can hEGFR be considered a protooncogene and how might become an oncogene? |
protooncogene b/c it is a growth-stimulating gene
can become oncogene if its activity starts to result in uncontrolled growth
|
Gene A loses activity w/ certain mutation.
Is the normal gene a tumor suppressor, oncogne, anti-oncogne, or proto-oncogene? |
tumor suppressor and anti-oncogene for both normal and mutant genes |
characteristics of matrix metalloproteinases and involved in what cancerous process |
protein/enzymes that require a metal (Zn or Ca) ion to break down proteins in ECM of cell
involved in metastasis |
Tumorigenic cells for cancer therapy |
only some cells in tumor can generate new tumor
if can treat or cut out those cells, then localize tumor and control metastasis |
Unique Characteristic of PARs |
proteolytically remove N-terminus of receptor itself and new N-terminus is the ligand that activates receptor |
Kd |
[ligand] for 1/2 max occupancy of receptors
measure affinity of ligand for receptor |
EC50 |
[ligand] for 1/2 max response
effectiveness in eliciting cellular response |
largest superfamily of receptors |
GPCRs |
What family of receptors facilitates addiction to tobacco? |
ionotropic nicotinic Ach-R |
Differences and Similarities in Intracellular Receptors |
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) |
concentration of albumin in serum |
4 g/dL |
4 functions of plasma albumin |
fatty acid transport
bilirubin transport
transport of steroid hormones
transport of sulta drugs, penicillin, aspirin |
Plasma protein degraded randomly at a rate of 100%/day. What is biological half life? |
0.693 days |
most abundant alpha-1 globulin?
Function?
Clinical result of its absence? |
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 |
organ albumin is synthesized in |
liver |
major class of proteins NOT synthesized in liver |
immunoglobulins |
most abundant of plasma proteins |
albumin |
how are fatty acids transported in plasma |
bound to albumin |
major fetal plasma protein |
alpha-1 fetoglobulin |
plasma protein that binds and transports iron |
transferrin |
plasma protein that binds and transports cortisol |
cortisol-binding globulin (alpha-1 globulin)
|
plasma protein that binds and transports vitamin A derivitives |
retinol-binding protein (alpha-1 globulin) |
plasma protein that binds and transports testosterone |
sex hormone binding globulin (SHBG)
beta-globulin |
plasma protein that binds and transports bilirubin |
albumin |
What ahppens to free hemoglobin in plasma? |
degraded by reticulothelial cells |
What would happen to hemoglobin in plasma if haptoglobin were absent? |
iron would be lost due to Hb breakdown.
Hb is lost through the kidney and excreted in urine. |
blue protein and what is its function |
ceruloplasmin
blue b/c of copper
oxidize Fe 2+ Fe 3+ in plasma
low levels found in Wilson's disease |