question

Lesch-Nyhan Syndrome

answer

HGPRT (hypoxanthine guanine phosphoribose transferase) deficiency. self mutilation. hyperuricemia. Early death X-linked recessive

question

Severe combined immunodeficiency

answer

ADA deficiency (Adenosine deaminase deficiency)

question

orange crystal in diaper

answer

earliest sign of Lesch Nyhan syndrome.

question

urea cycle

answer

orotic aciduria. hyperammonimia. what pathway is affected?

question

pyrimidine synthesis

answer

orotic aciduria. no hyperammonimia. what pathway is affected? Megaloblastic anemia.

question

Pentose phosphate pathway / HMP shunt

answer

R5P is derived at?

question

PRPP to 5-phosphoribosylamine by PRPP amidotransferase

answer

RLS of Purine synthesis

question

formation of carbamoyl phosphate by CPS-1

answer

RLS of pyrimidine synthesis

question

IMP

answer

precursor of AMP and GMP

question

Ceruloplasmin

answer

Serum enzyme level use to diagnose hepatolenticular degeneration. Wilsons disease.

question

Free energy

answer

Predict whether a reaction is spontaneous or not.

question

Entropy

answer

Measure the change in randomness of a reactant.

question

Exergonic

answer

Energy released. Spontaneous. Negative free energy.

question

Endergonic

answer

Energy required. Not spontaneous. Positive free energy.

question

Complex 2 - succinate DH

answer

ETC, part of krebs cycle

question

Coenzyme Q/ ubiquinone

answer

The only non-protein part of ETC

question

Complex 3

answer

Fe/Heme protein

question

Complex 4

answer

Cu/heme protein

question

Complex 5

answer

Oxidative phosphorylation

question

Inihibits cytochrome oxidase

answer

MOA of amyl oxidase Antidote for cyanide poisoning.

question

Complex 4

answer

Cytochrome oxidase

question

Uncouplers

answer

Inc permeability of innet mitochondrial membrane Proton gradient is lost without passing through the ATP synthase complex.

question

Aspirin and thermogenin of brown fat

answer

Sample uncoupler.

question

2 ATP

answer

How many ATP used during energy investment in glycolysis?

question

4ATP

answer

How many ATP produced in energy generation in glycolysis?

question

Chronic alcoholism

answer

Acquired pyruvate DH deficiency

question

cytosol

answer

site of glycogenesis

question

cytoplasm

answer

site of glycogenolysis

question

UDP-galactose

answer

activated form of galactose

question

galactokinase deficiency

answer

cataract in early childhood

question

Gal-1-P uridyltransferase deficiency

answer

cataract within few days after birth

question

glycolysis

answer

aldolase A can be found at?

question

fructose metabolism

answer

aldolase B can be found at?

question

galacticol

answer

what substance accumulate in lens of a cataract patient with classic galactosemia?

question

sorbitol

answer

what substance accumulates in lens of a cataract patient with DM?

question

cytoplasm

answer

site of PPP/HMP shunt.

question

NONE

answer

how many ATP produced in HMP shunt?

question

NONE

answer

how many ATP consumed in HMP shunt?

question

R5P Glyceraldehyde 3 PO4 NADPH

answer

products of HMP shunt

question

thiamine

answer

co-factor of transketolase in HMP shunt

question

RBC transketolase activity

answer

diagnostic of thiamine deficiency

question

selenium

answer

co-factor of glutathione peroxidase in removal of H2O2.

question

bite cell

answer

phogocytic removal of heinz body in RBC will yield to?

question

heinz body

answer

altered hemoglobin that precipitate within RBC

question

linoleic acids

answer

arachidonic acid becomes essential in the absence of?

question

cytosol

answer

site of fatty acid synthesis / lipogenesis

question

palmitate

answer

product of fatty acid synthesis

question

biotin

answer

co-factor in the RLS of fatty acid synthesis *acetyl CoA carboxylase

question

mitchondrial matrix

answer

site of acetyl CoA production

question

panthothenic acid

answer

co-factor present together with ACP

question

DHAP of glycolysis

answer

synthesis of TAG in adipose came from?

question

liver and adipose

answer

what organ does FA synthesize?

question

citrate shuttle

answer

how acetyl CoA reach cytosol from mitochondria?

question

carnitine shuttle

answer

how does faty acyl CoA reach mitochondria from cytosol?

question

SER

answer

where does steroid hormone synthesis occurs?

question

cholesterol-7-alpha-hydroxylase

answer

RLS of bile acid synthesis

question

Lysine and threonine

answer

All AA must transfer their amino group to alpha ketoglutarate to form glutamate except?

question

Vitamin B6 [pyridoxal phosphate]

answer

Co enzyme in transamination

question

Glutamate DH

answer

Enzyme for oxidative deamination

question

Liver

answer

Urea cycle occurs in what organ?

question

Composition of lipoproteins?

answer

varying proportions of cholesterol, trgs, and phospholipids. LDL and HDL carry most cholesterol

question

Function of LDL?

answer

transports cholesterol from liver to tissues

question

function of HDL?

answer

transports cholesterol from periphery to liver

question

function of chylomicrons?

answer

delivers dietary trgs to peripheral tissue & delivers cholesterol to liver in form of chylomicron remnants (mostly TRG depleted)

question

where are chylomicrons secreted?

answer

intestinal epithelial cells

question

function of vLDLs?

answer

delivers hepatic TRGs to peripheral tissue

question

where are vLDLs secreted?

answer

liver

question

function of idls?

answer

delivers trgs and cholesterol to liver. formed by degradation of vdl

question

function of ldls?

answer

delivers hepatic cholesterol to peripheral tissues

question

where are ldls formed?

answer

formed by hepatic lipase modification of IDL in the peripheral tissue

question

how are ldls taken up?

answer

taken up target cells via receptor mediated endocytosis

question

role of hdls?

answer

mediates reverse cholesterol transport from periphery to liver & acts as a repository for apoC and apoE (which are needed for chylomicron and VLDL metabolism)

question

where are hdls secreted?

answer

secreted from both liver and intestine

question

Lab findings of Type I familial dyslipidemia?

answer

Increased chylomicrons, trgs, and cholesterol (hyper-chylonmicronemia)

question

Inheritance of type I familal dyslipidemia?

answer

Autosomal recessive (hyper-chylonmicronemia)

question

Defect in type I familial dyslipidemia?

answer

Lipoprotein lipase deficiency OR altered apolipoprotein C-II (hyper-chylomicronemia)

question

Symptoms/physical findings of type I familial dyslipidemia?

answer

Pancreatitis, hepatosplenomegaly, eruptive/pruritic xanthomas BUT NO increased risk for atherosclerosis . (hyper-chylomicronemia)

question

Lab findings of Type IIa familial dyslipidemia?

answer

Increased LDL, cholesterol (familial hypercholesterolemia)

question

Inheritance of type IIa familal dyslipidemia?

answer

autosomal dominant

question

Defect in type IIa familial dyslipidemia?

answer

absent or decreased LDL receptors

question

Symptoms/physical findings of type IIa familial dyslipidemia?

answer

accelerated atherosclerosis, tendon (esp achilles) xanthomas, and corneal arcus (familial hypercholesterolemia)

question

Lab findings of Type IV familial dyslipidemia?

answer

increased VLDL and TRGs (familial hypertriglyceridemia)

question

Inheritance of type IV familal dyslipidemia?

answer

autosomal dominant (familial hypertriglyceridemia)

question

Defect in type IV familial dyslipidemia?

answer

hepatic overproduction of VLDL (familial hypertriglyceridemia)

question

Symptoms/physical findings of type IV familial dyslipidemia?

answer

pancreatitis (familial hypertriglyceridemia)

question

Inheritance of abetalipoproteinemia?

answer

autosomal recessive

question

Defect in abetalipoproteinemia?

answer

mutation in microsomal trg transfer protein (MTP) gene -> decreased B-48 and B-100 -> decreased chylomicron and VLDL synthesis and secretion

question

When do symptoms of abetalipoproteinemia occur?

answer

W/in the first few months of life

question

Biopsy findings of abetalipoproteinemia?

answer

Intestinal biopsy shows lipid accumulation w/in enterocytes due to inability to export absorbed lipid as chylomicron

question

Symptoms/physical findings of abetalipoproteinemia?

answer

failure to thrive, steatorrhea, acanthocytosis, ataxia, night blindness

question

Function of pancreatic lipase?

answer

degradation of dietary TRGs in small intestine

question

function of lipoprotein lipase?

answer

degradation of TRGs circulating in chylomicrons and VLDLs

question

function of hepatic TG lipase?

answer

degradation of TRGs remaining in IDL

question

function of hormone sensitive lipase?

answer

degradation of TRG stored in adipocytes

question

function of lecithin cholesterol acetyl transferase (LCAT)?

answer

catalyzes esterification of cholesterol

question

function of cholesterol ester transfer protein (CETP)?

answer

mediates transfer of cholesterol esters to other lipoprotein particles

question

role of Apolipoprotein E?

answer

mediates remnant uptake

question

where is apolipoprotein E found?

answer

chylomicrons. Chylomicron remanants, VLDL, IDL, HDL

question

role of Apolipoprotein A-I?

answer

activates lecithin cholesterol acetyl transferase (LCAT)

question

where is apolipoprotein A-I found?

answer

HDL

question

role of Apolipoprotein C-II?

answer

lipoprotein lipase cofactor

question

where is apolipoprotein C-II found?

answer

chylomicrons, VLDL, HDL

question

role of Apolipoprotein B-48?

answer

mediates chylomicron secretion

question

where is apolipoprotein B-48 found?

answer

chylomicrons and chylomicron remnants

question

role of Apolipoprotein B-100?

answer

binds LDL receptor

question

where is apolipoprotein B-100 found?

answer

VLDL, IDL, and HDL

question

Energy source in the first few seconds of exercise?

answer

Stored ATP (decreases quickly) and creatine phosphate (quick rise and fall after stored ATP)

question

energy source for minutes long exercise?

answer

primary=anaerobic glycolysis, secondary=aerobic metabolism and FA oxidation

question

energy source for hours long exercise?

answer

1ary=aerobic metabolism and FA oxidation; 2ary=anaerobic glycolysis

question

what is the body's priority during fasting and starvation states?

answer

supply sufficient glucose to the brain and RBCs; preserve protein

question

Amount of energy stored in 1g carbs?

answer

4 kcal

question

Amount of energy stored in 1g protein?

answer

4 kcal

question

Amount of energy stored in 1g fat?

answer

9 kcal

question

Primary source of energy in fed state? (post prandial)

answer

glycolysis and aerobic respiration; Insulin stimulates storage of lipids, proteins, and glycogen

question

Primary source of energy in fasted state (b/w meals)?

answer

Major=hepatic glycogenolysis, minor=hepatic gluconeogenesis AND adipose release of FFA. Glucagon and adrenaline stimulate use of fuel reserves

question

Primary source of energy in 1-3 days starvation?

answer

hepatic glycogenolysis, adipose release of FFA.

question

What change takes place in the muscle and liver during 1-3 days of starvation?

answer

shift fuel use from glucose to FFA

question

What contributes to hepatic gluconeogenesis during 1-3 days of starvation?

answer

peripheral tissue lactate and alanine, glycerol and propionyl-coA from adipose tissue (from odd chain FFA-only trg components that contribute to gluconeogenesis)

question

How long does it take glycogen reserves to be depleted in starvation?

answer

Glycogen reserves depleted after day 1

question

Can RBCs use ketones for fuel?

answer

NO! because they lack mitochondria

question

Energy source in starvation greater than 3 days?

answer

Adipose stores (ketone bodies become main energy source for brain+heart); post adipose-deletion, vital protein degradation accelerates leading to organ failure and death

question

What determines survival time in starvation?

answer

amount of adipose stores

question

rate limiting step of cholesterol synthesis?

answer

HMG-CoA reductase catalyzed conversion of HMG-CoA to mevalonate

question

What enzyme esterifies plasma cholesterol?

answer

2/3 of plasma cholesterol is esterified by lecithin-cholesterol acyltransferase (LCAT)

question

Where does fatty acid degradation occur?

answer

mitochondria-where the products will be consumed

question

Findings of acyl-coA dehydrogenase deficiency?

answer

Increased dicarboxylic acids, decreased glucose and ketones. Presents w/severe hypoglycemia

question

defect in carnitine deficiency?

answer

inability to transport LCFAs into the mitochondria -> toxic accumulation

question

Symptoms/physical findings of carnitine deficiency?

answer

weakness, hypotonia, hypoketotic hypoglycemia and cardiomyopathy (b/c heart needs carnitine)

question

what in the mitochondrial membrane needs to be active for fatty acid synthesis?

answer

Citrate shuttle (citrate=synthesis)

question

what in the mitochondrial membrane needs to be active for fatty acid degradation?

answer

carntitine shuttle

question

What are fatty acids and amino acids metabolized to in the liver?

answer

acetoacetate and beta-hydroxybutyrate (to be used in muscle+brain)

question

What molecule used for gluconeogenesis is depleted in prolonged starvation and DKA?

answer

oxaloacetate. Leads to stalling of TCA cycle which shunts glucose and FFA towards production of ketone bodies

question

Which molecules are found in excess in alcoholism?

answer

NADH and malate (excess NADH shunts oxaloacetate to malate). Stalls TCA cycle shunting glucose and FFA towards production of ketone bodies

question

What are ketone bodies made from?

answer

HMG-CoA

question

What are ketone bodies metabolized to in the brain?

answer

2 molecules of acetyl-coA

question

How are ketone bodies excreted?

answer

urine (but urine test for ketones does not detect betahydroxybutyrate which is favored by a high redox state!)

question

Findings in Fabry's disease?

answer

peripheral neuropathy of hand/feet, angiokeratomas, cardiovascular/renal dz

question

Deficient enzyme in Fabry's disease?

answer

alpha-galactosidase A

question

accumulated substrate in Fabry's disease?

answer

ceramide trihexosidase

question

inheritance of fabry's disease?

answer

X-linked recessive

question

Findings in Gaucher's disease?

answer

Hepatosplenomegaly, aseptic necrosis of femur, bone crises, Gaucher's cells (macrophages that look like crumpled tissue paper) *most common sphingolipidosis*

question

Deficient enzyme in Gaucher's disease?

answer

glucocerebrosidase

question

Accumulated substrate in Gaucher's dz?

answer

glucocerebroside

question

Inheritance in Gaucher's dz?

answer

Autosomal recessive

question

Findings in Niemann-Pick dz?

answer

progressive neurodegeneration, hepatosplenomegaly, cherry red spot on macula, foam cells

question

deficient enzyme in Niemann-Pick dz?

answer

sphingomyelinase

question

Accumulated substrate in Niemann-Pick dz?

answer

sphingomyelin

question

Inheritance in Niemann-Pick dz?

answer

autosomal recessive

question

Findings in Tay-Sachs dz?

answer

progressive neurodegeneration, developmental delay, cherry red spot on macula, lysosomes w/onion skin. NO hepatosplenomegaly

question

Deficient enzyme in Tay-Sachs disease?

answer

Hexosaminidase A

question

Accumulated substrate in Tay-Sachs dz?

answer

GM2 ganglioside

question

Inheritance in Tay-Sachs dz?

answer

autosomal recessive

question

Findings in Krabbe's dz?

answer

peripheral neuropathy, developmental delay, optic atrophy, globoid cells

question

Deficient enzyme in Krabbe's dz?

answer

galctocerebrosidase

question

accumulated substrate in krabbe's dz?

answer

galactocerebroside

question

inheritance in Krabbe's dz?

answer

autosomal recessive

question

findings in metachromatic leukodystrophy?

answer

central and peripheral demyelination w/ataxia, dementia

question

deficient enzyme in metachromatic leukodystrophy?

answer

arylsulfatase A

question

accumulated substrate in Krabbe's dz?

answer

cerebroside sulfate

question

Inheritance in metachromatic leukodystrophy?

answer

autosomal recessive

question

Findings in Hurler's syndrome?

answer

developmental delay, gargoylism, airway obstruction, corneal clouding, hepatosplenomegaly

question

Deficient enzyme in Hurler's syndrome?

answer

alpha-L-iduronase

question

accumulated substrate in Hurler's syndrome?

answer

Heparan sulfate and dermatan sulfate

question

inheritance in Hurler's syndrome ?

answer

autosomal recessive

question

findings in Hunter's syndrome?

answer

mild Hurler's + aggressive behavior BUT no corneal clouding

question

deficient enzyme in Hunter's syndrome?

answer

iduronate sulfatase

question

Accumulated substrate in Hunter's syndrome?

answer

Heparan sulfate and dermatan sulfate

question

inheritance in Hunter's syndrome ?

answer

X-linked recessive

question

Which lysosomal storage diseases are more common in the Ashkenazi Jewish population?

answer

Tay-sachs, Niemann-Pick, some forms of Gaucher's dz

question

Findings in von Gierke's dz?

answer

severe fasting hypoglycemia, very increased glycogen in liver, increased blood lactate, hepatomegaly (=type I glycogen storage dz)

question

deficient enzyme in von Gierke's dz?

answer

glucose-6-phosphatase

question

Inheritance of von Gierke's dz?

answer

autosomal recessive

question

Findings in Pompe's dz?

answer

cardiomegaly, systemic findings leading to early death (=type II glycogen storage disease)

question

Deficient enzyme in Pompe's disease?

answer

lysosomal alpha-1,4-glucosidase (acid maltase)

question

Inheritance of Pompe's dz?

answer

autosomal recessive (*Pompe's trashes the pump*)

question

Findings in Cori's disease?

answer

Milder form of type I/Von Gierke's dz with normal lactate levels (=type III glycogen storage dz) Gluconeogenesis is intact

question

deficient enzyme in Cori's disease?

answer

debranching enzyme=alpha-1,6-glucosidase

question

Inheritance of Cori's disease?

answer

autosomal recessive

question

Findings in McArdle's dz?

answer

increased glycogen in muscle but can't break down->painful muscle cramps, myoglobinuria with strenuous exercise (=Type V glycogen storage dz)

question

deficient enzyme in McArdle's dz?

answer

skeletal muscle glycogen phosphorylase

question

Inheritance of McArdle's dz?

answer

autosomal recessive

question

Types of bonds present in glycogen?

answer

branches have alpha-1,6-bonds, linkages have alpha-1,4-bonds

question

When is glycogen in skeletal muscle used?

answer

Rapidly metabolized during exercise. Glycogen->glycogenolysis-> glucose-1-phosphate->glucose-6-phosphate

question

Findings in all forms of cystinuria?

answer

Excess homocysteine in urine resulting in cysteine becoming essential, mental retardation, osteoporosis, tall stature, kyphosis, lens subluxation (down and in), atherosclerosis->stroke,MI

question

Inheritance of all forms of homocystinuria?

answer

autosomal recessive

question

Defects causing homocystinuria?

answer

1. Cystathionine synthase deficiency 2.decreased affinity of cystathionine synthase for pyridoxal phosphate 3. homocysteine methyltransferase deficiency (req B12 as cofactor)

question

Tx for homocystinuria due to cystathionine synthase deficiency?

answer

decrease methionine and increase cysteine, B12, and folate in diet

question

Tx for homocystinuria due to decreased affinity of cystathionine synthase for pyridoxal phosphate?

answer

Greatly increase vitamin B6 in diet

question

Defect in cystinuria?

answer

defect of renal tubular amino acid transporter for cysteine, ornithine, lysine, and arginine in PCT of kidneys

question

Findings in cystinuria?

answer

excess cysteine in urine-> precipitation of hexagonal crystals-> renal staghorn calculi

question

Treatment and inheritance of cystinuria?

answer

good hydration and urinary alkalinization. Autosomal recessive. Common!

question

What is cystine?

answer

2 cysteines connected by a disulfide bond

question

Defect in maple syrup urine dz?

answer

blocked degradation of branched amino acids (Ile, Leu, Val) due to decreased alpha-ketoacid dehydrogenase (B1)->increased alpha-ketoacids in blood (esp Leu)

question

Findings in maple syrup urine dz?

answer

severe CNS defects, mental retardation, death. Autosomal recessive inheritance

question

Defect in Hartnup dz?

answer

defective neutral amino acid transporter on renal and intestinal epithelial cells

question

Findings in Hartnup dz?

answer

tryptophan excretion in urine + decreased absorption in gut->pellagra

question

defect in phenylketonuria?

answer

decreased phenylalanine hydroxylase or decreased tetrahydrobiopterin cofactor (malignant PKU)

question

Findings in PKU?

answer

mental and growth retardation, seizures, fair skin, eczema, musty body odor, excess phenylketones in urine (due to excess phenylalanine)

question

Treatment for pku?

answer

decrease phenylalanine in diet (contained in aspartame), increase tyrosine in diet

question

What is maternal PKU?

answer

lack of proper dietary therapy in pregnancy. Findings in infant: microcephaly, mental and growth retardation, congenital heart dz

question

inheritance of pku?

answer

autosomal recessive

question

what are the 3 phenylketones?

answer

phenylacetate, phenyllactate, phenylpyruvate

question

defect in alkaptonuria (ochronosis)?

answer

deficiency of homogentisic acid oxidase in the degradative pathway of tyrosine to fumarate. Autosomal recessive

question

findings in alkaptonuria?

answer

dark connective tissue, brown pigmented sclera, urine turns black on prolonged exposure to air. Benign disease. May have debilitating arthralgias (homogentisic acid toxic to cartilage)

question

2 defects possible in albinism?

answer

1. Deficiency of tyrosinase (inability to synthesize melanin from tyrosine). Autosomal recessive. 2. Defective tyrosine transporters (decrease amounts of tyrosine therefore melanin). *can also result from a lack of migration of neural crest cells)

question

What are pts with albinism at increased risk for?

answer

skin cancer 2/2 lack of melanin

question

Inheritance of albinism?

answer

variable inheritance due to locus heterogeneity (unlike ocular albinism which is x-linked recessive)

question

Possible defects leading to hyperammonemia?

answer

1. acquired (liver dz.) 2. Hereditary (urea cycle enzyme deficiencies). Both result in excess NH4+ ->depletion of alpha-ketoglutarate->inhibition of TCA cycle

question

Treatment for hyperammonemia?

answer

Limit protein in diet. Benzoate or phenylbutyrate (both bind amino acid and lead to excretion so decrease nh4 levels). Lactulose to acidify the GI tract and trap nh4+ for excretion

question

Symptoms/physical findings of hyperammonemia?

answer

tremor/asterixis, slurring of speech, somnolence, voming, cerebral edema, blurring of vision

question

inheritance of orithine transcarbamoylase deficiency?

answer

Xlinked recessive (unlike other urea cycle disorders that are autosomal recessive). Most common urea cycle disorder

question

defect in ornithine transcarbamoylase deficiency?

answer

excess carbamoyl phosphate converted to orotic acid (part of pyrimidine synthesis pathway) due to lack of enzyme. Inability to eliminate ammonia

question

findings in ornithine transcarbamoylase deficiency?

answer

Increased orotic acid in blood and urine, decreased BUN, symptoms of hyperammonemia. Usually presents in 1st few days, may present w/late onset

question

What are the important derivatives of phenylalanine?

answer

uses BH4 to make tyrosine (thyroxine) and dopa (melanin), B6+dopa->dopamine. Add vitamin C to dopamine->NE, add SAM ->epi

question

Important derivatives of tryptophan?

answer

1. NAD+/NADH (w/B6 and niacin) 2. Melatonin (add BH4 to serotonin)

question

Important derivatives of histidine?

answer

Add histamine (req B6)

question

Important derivatives of glycine?

answer

Heme. Intermediate step req B6 and makes porphyrin

question

Important derivatives of arginine?

answer

1. Creatine 2.Urea 3. Nitric oxide

question

Important derivatives of glutamate?

answer

1. GABA (req B6) 2. Glutathione

question

glucogenic essential amino acids?

answer

Met, Val, His

question

Glucogenic/Ketogenic essential amino acids?

answer

Ile, Phe Thr,Trp

question

Ketogenic essential amino acids?

answer

Leu, Lys

question

Acidic amino acids?

answer

Asp, Glu (negatively charged at body pH)

question

Basic amino acids?

answer

Arg, Lys, His (arg=most basic. His=neutral at body pH)

question

When are Arg and His required in the diet?

answer

during periods of growth

question

Which amino acids are found in increased concentration in histones?

answer

Arg, His b/c they are positive and bind negatively charged DNA

question

Features of galactokinase deficiency?

answer

Galactitol accumulates (if galactose present). Relatively mild, autosomal recessive

question

Defect in classic galactosemia?

answer

absence of galactose-1-phosphate uridyl transferase resuls in accumulation of toxic substances including galactitol (lens of eye)

question

Symptoms of classic galactosemia?

answer

failure to thrive, jaundice, hepatomegaly, infantile cataracts, mental retardation

question

Treatment of classical galactosemia?

answer

exclude galactose and lactose (=galactose+glucose) from diet

question

What cells/tissues are prone to accumulation of sorbitol? Why?

answer

scwann cells, retina, kidneys. B/c they lack the enzyme to convert sorbitol to fructose (=sorbitol dehydrogenase). They only have aldose reductase

question

What metabolic condition predisposes to accumulation of sorbitol?

answer

High blood levels of glucose OR galactose (sorbitol =sugar alcohol, alt method for trapping glucose in cell)

question

Symptoms of lactase deficiency?

answer

bloating, cramps, osmotic diarrhea. All due to loss of brush border enzyme (disaccharidase)

question

Who is lactase deficiency most common in?

answer

african americans, asians.

question

Consequences of glucose-6-phosphate dehydrogenase deficiency?

answer

NADPH is necc. to keep glutathione reduced->detoxifies free radicals + peroxides. Decreased NADPH in RBCs->hemolytic anemia (poor RBC defense against oxidizing agents incl fava beans, sulfonamides, primaquine, TB drugs). Hemolysis may also follow infectin

question

Inheritance of glucose-6-phosphate dehydrogenase deficiency?

answer

x linked recessive. Most common human enzyme deficiency b/c increases malarial resistance

question

Blood smear findings in glucose-6-phosphate dehydrogenase deficiency?

answer

1. Heinz bodies=oxidized hemoglobin precipitated w/in RBCs 2. Bite cells-resulting from phagocytic removal of Heinz bodies by splenic macrophages

question

Defect in essential fructosuria?

answer

defect in fructokinase

question

Symptoms of essential fructosuria?

answer

Asymptomatic->fructose appears in blood and urine. Benign b/c fructose not trapped in cells

question

Inheritance of essential fructosuria?

answer

autosomal recessive

question

Defect in fructose intolerance?

answer

Heredtary deficiency of aldolase B-> fructose-1-phosphate accumulates->decrease in available phosphate->inhibition of glycogenolysis+gluconeogenesis

question

Inheritance of fructose intolerance

answer

autosomal recessive

question

Symptoms of fructose intolerance?

answer

hypoglycemia, jaundice, cirrhosis, vomiting

question

Treatment of fructose intolerance?

answer

decreased intake of both fructose and sucrose (glucose+fructose)

question

Name 4 electron transport inhibitors?

answer

1. Rotenone 2. Cyanide 3. Antimycin A 4. CO

question

Consequence of poisoning w/e-transport inhibitor?

answer

directly inhibits electron transport->decreased proton gradient->block of ATP synthesis

question

Oligomycin

answer

ATP synthase inhibitor

question

Consequence of oligomycin?

answer

directly inhibits mitochondrial atp synthase-> increases proton gradient. NO ATP produced b/c electron transport stops

question

Name 3 uncoupling agents.

answer

1. 2,4 DNP 2. aapirin (fevers often occur in aspirin OD) 3. thermogenin in brown fat

question

Consequences of uncoupling agents?

answer

Increased permeability of membrane -> decreased proton gradient-> increased O2 consumption. ATP synth stops, but e- transport continues. Produces heat

question

Role of pyruvate kinase?

answer

irreversible enzyme in gluconeogenesis. In mitochondira converts pyruvate to oxaloacetate.

question

Cofactors for pyruvate kinase?

answer

Biotin. Also requires ATP and activation by acetyl-CoA

question

Role of PEP Carboxykinase?

answer

Irreversible enzyme in gluconeogenesis. In cytosol converts oxaloacetate->phosphoenolpyruvate. Req GTP

question

role of Fructose-1,6-bisphosphatase?

answer

irreversible enzyme in gluconeogenesis. In cytosol. Converts fructose-1,6-bisphosphate->fructose-6-p

question

Role of glucose-6-phosphatase?

answer

Irreversible enzyme in gluconeogenesis. In ER. Converts glucose-6-p->glucose.

question

What type of fatty acid can serve as a substrate for gluconeogenesis? Why?

answer

Odd chain fatty acids (yield 1 propionyl coA which can enter TCA cycle as succinyl coA and then undergo gluconeogenesis). Even chain fatty acids cannot produce new glucose b/c they only produce acetyl-coA equivalents

question

Why does muscle not participate in gluconeogenesis?

answer

Lack of glucose-6-phosphatase

question

Primary location of gluconeogenesis?

answer

Liver. Enzymes also found in kidney, intestinal epithelium.

question

Defect in pyruvate dehydrogenase complex deficiency?

answer

Most cases due to mutation in xlinked gene for E1-alpha subunit of PDC

question

consequecne of pyruvate dehydrogenase complex deficiency?

answer

causes backup of pyruvate and alanine resulting in lactic acidosis

question

Findings in pyruvate dehydrogenase complex deficiency?

answer

neurologic deficits, usually starting in infancy, severe acidosis, hypoglycemia, vomiting, hypotonia

question

treatment of pyruvate dehydrogenase deficiency?

answer

increase intake of ketogenic nutrients (high fat content) or increase lysine and leucine

question

Findings in arsenic poisoning?

answer

vomiting, rice water stools, garlic breath. Due to inhibition of lipoic acid

question

Enzymes and cofactors required by pyruvate dehydrogenase complex?

answer

1. pyrophosphate (b1,thiamine, tpp) 2.FAD (b2,riboflavin) 3. NAD (B3, niacin) 4. CoA (B5,pantothenate) 5.Lipoic acid

question

Changes in pyruvate dehydrogenase complex activated by exercise?

answer

1. Increased NAD+/NADH ratio 2. Increased ADP 3. Increased Ca2+

question

1st step of glycolysis?

answer

Phosphorylation of glucose->glucose-6-p catalyzed by either hexokinase or glucokinase

question

Hexokinase?

answer

Ubiquitous phosphorylator of glucose. High affinity, Low Km, low capacity, low Vmax, uninduced by insulin, feedback inhibited by glucose-6-phosphate

question

Glucokinase?

answer

Phospylator of glucose in liver and beta cells of pancreas. Low affinity, high Km, high capacity, high Vmax, induced by insulin. At low glucose []s hexokinase sequesters glucose in tissue. At high glucose []s. excess glucose is stored in liver

question

Universal e- acceptors?

answer

Nicotinamides. 1. NAD+ generally used in catabolic processes 2. NADPH used in anabolic processes as a supply of reducing equivalents.

question

where is nadph made?

answer

hmp shunt

question

4 uses for NADPH?

answer

1. Anabolic processes 2. respiratory burst 3. P450 4.Glutathione reductase

question

Where is the malate-aspartate shuttle and what is its function?

answer

Heart and liver. Makes 32 ATP by active metabolism of glucose

question

Where is the glycerol-3-phosphate shuttle and what is its function?

answer

Muscle, produces 30 ATP

question

Rate limiting enzyme of glycolysis?

answer

Phosphofructokinase-1=PFK1. Regulated pos by AMP, fructose-2,6-BP inhibited by ATP, citrate

question

rate limiting enzyme of gluconeogenesis?

answer

Fructose-1,6-bisphosphatase. Pos reg by ATP. Inhib by AMP, fructose-2,6-BP

question

rate limiting enzyme of TCA cycle?

answer

isocitrate dehydrogenase. Pos reg by ADP, inhib by ATP, NADH

question

rate limiting enzyme of glycogen synthesis?

answer

glycogen synthase. Pos reg by glucose, insulin. Inhib by glucagon, epinephrine

question

rate limiting enzyme of glycogenolyisis?

answer

glycogen phosphorylase. Pos reg by AMP, epinephrine, glucagon. Inhib by insulin, atp

question

rate limiting enzyme of HMP shunt?

answer

glucose-6-phosphate dehydrogenase (G6PD). Pos reg by NADP+. Inhib by NADPH

question

rate limiting enzyme of de novo pyrimidine synthesis?

answer

Carbamoyl phosphate synthetase II

question

rate limiting enzyme of de novo purine synthesis?

answer

Glutamine-PRPP amidotransferase. Inhib by AMP, IMP, GMP

question

rate limiting enxyme of urea cycle?

answer

carbamoyl phosphate synthetase I. Pos reg by N-acetylglutamate

question

rate limiting enzyme of fatty acid synthesis?

answer

Acetyl-coA carboxylase (ACC). Pos reg by insulin, citrate. Inhib by glucagon, palmitoyl-CoA

question

rate limiting enzyme of fatty acid oxidation?

answer

Carnitine acyltransferase I. Inhib by malonyl coA

question

rate limiting enzyme of Ketogenesis?

answer

HMG-CoA synthase

question

rate limiting enzyme of cholesterol synthesis?

answer

HMG-CoA reductase. Pos reg by insulin, thyroxine. Inhib by glucagon, cholesterol

question

Cause and findings of kwashiorkor?

answer

protein malnutrition->skin lesions, edema, liver malfunction (fatty change due to apolipoprotein synthesis)

question

Clinical picture of kwashiorkor?

answer

Small child w/swollen belly

question

Cause and findings of marasmus?

answer

energy malnutrition->tissue and muscle wasting, loss of subcutaneous fat, variable edema

question

What metabolic processes take place in the mitochondria?

answer

fatty acid oxidation (beta-oxidation), acetyl-CoA production, TCA cycle, oxidative phosphorylation

question

What metabolic processes take place in the cytoplasm?

answer

Glycolysis, fatty acid synthesis, HMP shunt, protein synthesis (RER), steroid synthesis (SER), cholesterol synthesis

question

What metabolic processes take place in both the cytoplasm and mitochondria?

answer

Heme synthesis, urea cycle, gluconeogenesis

question

What is the function of vitamin k?

answer

catalyzes gamma-carboxylation of glutamic acid residues on various proteins concerned with blood clotting

question

Where is vitamin K synthesized?

answer

Intestinal flora

question

Findings of vitamin K deficiency?

answer

Neonatal hemorrhage w/increased PT and PTT but normal bleeding time. May also occur after prolonged use of broad spectrum antibiotics

question

Why are neonates given vitamin K?

answer

To prevent hemorrhage-vit k is not in breast milk, and neonates have sterile intestines and are unable to synth vit k

question

Function of zinc?

answer

essential for the activity of 100+ enzymes and important in the formation of zinc fingers (transcription factor motif)

question

Findings of zinc deficiency?

answer

delayed wound healing, hypogonadism, decreased adult (axillary, pubic, facial) hair, dysgeusia, anosmia, may predispose to alcoholic cirrhosis

question

Limiting reagent of ethanol metabolism?

answer

NAD+

question

What type of kinetics does alcohol dehydrogenase operate under?

answer

zero order

question

What is fomeprizole?

answer

inhibits alcohol dehydrogenase and is an antidote for methnol or ethylene glycol poisoning

question

What is disulfiram?

answer

Inhibits acetaldehyde dehydrogenase->accum of acetaldehyde-> hangover symptoms

question

Physiology of ethanol hypoglycemia?

answer

etoh metabolism increases NADH/NAD+ in liver->diversion of pyruvate to lactate and OAA to malate->inhibition of gluconeogenesis & stim fatty acid synth->hypoglycemia and hepatic steatosis. Over production of lactate may lead to acidosis.. Depletion of oxaloacetate shuts down TCA cycle->acetyl coA to ketone production. breakdown of excess malate increases NADPH->increased fatty acid synthesis

question

Function of vitamin C?

answer

antioxidant, facailitates iron absorption by keeping iron in Fe2+ reduced state, necc for hydroxylation of proline+lysine in collagen synth, necc for dopamine beta-hydroxylase which converts dopamine to NE

question

Vitamin C deficiency?

answer

scurvy=swollen gums, bruising, hemarthrosis, anemia, poor wound healing, weakened immune response

question

Vitamin C excess?

answer

nausea, vomiting, diarrhea, fatigue, sleep problems, can increase risk of iron toxicity in pts with hemachromatosis or transfusions

question

Describe the 4 forms of vitamin D.

answer

1. D2=ergocalciferol, ingested from plants. 2.D3=cholecalciferol, ingested from milk, formed in sunexposed skin 3. 25-OH D3=storage form 4. 1,25-(OH)2D3=calcitriol, active form

question

function of vitamin D

answer

Increased absorption of ca and phosphate->increased bone mineralization

question

Findings in vit D deficiency

answer

Rickets in children (bone pain+deformity), osteomalacia in adults (bone pain+muscle weakness), hypocalcemic tetany, breast milk has decr vitamin D (supplement in dark skinned pts)

question

Finding in Vitamin D excess

answer

hypercalcemia, hypercalciuria, loss of appetite, stupor, seen in sarcoidosis (2/2 incr activation of vitamin D by epitheliod macrophages)

question

Function of vitamin E

answer

Antioxidant (protects erythocytes and membranes from free radical damage)

question

Findings in vit E deficiency

answer

Increased fragility of erythrocytes (hemolytic anemia), muscle weakness, posterior column, and spinocerebellar tract demyelination

question

Function of vitamin B12

answer

cofactor for homocysteine methyltransferase (transfers CH3 groups as methylcobalamin) and methylmalonyl-coA mutase

question

Findings in Vit B12 deficiency

answer

Macrocytic, megaloblastic anemia, hypersegmented PMNs, neurologic symptoms (paresthesias, subacute combined degeneration) due to abnormal myelin. Prolonged deficiency leads to irreversible nervous system damage

question

Causes of vit B12 deficiency

answer

Usually caused by malabsorption (spue, entertitis, Diphyllobotrium latum), lack of intrinsic factor (pernicious anemia, gastric bypass surgery), or absence of terminal ileum (Crohn's disease). Usually found in animal products, synth only by microorgs. Several year reserve pool stored primarily in the liver

question

S-adenosyl-methionine

answer

ATP+methionine->SAM. SAM transfers methyl units. Regeneration of methionine (+therefore SAM) is dependent on vit B12 and folate. REQ for conversion of NE to epinephrine

question

Function of vitamin B7 (Biotin)

answer

cofactor for carboxylation enzymes (add a 1 carbon group). 1. Pyruvate carboxylase (Converts Pyruvate->oxaloacetate) 2. Acetyl-CoA carboxylase (Converts acetyl-CoA->malonylCoA) 3. Propionyl-CoA carboxylase (propionyl coA->methylmalonyl-CoA

question

Findings in B7/biotin deficiency

answer

Relatively rare. Dermatitis, alopecia, enteritis. Caused by antibiotic use or excessive ingestion of raw eggs (Avidin in egg whites avidly binds biotin)

question

Functions of B9/folic acid

answer

converted to tetrahydrofolate (THF) a coenzyme for 1-carbon transfer/methylaton rxns. Important for synthesis of nitrogen bases in DNA and RNA

question

Findings in B9/folic acid deficiency

answer

macrocytic, megaloblastic anemia, NO neurologic symptoms, most common vit deficiency in US. Seen in alcoholism and pregnancy.

question

Causes of B9/folic acid deficiency

answer

Alcoholism, pregnancy, drugs (phenytoin, sulfonamides, MTX)

question

Sources of folic acid/B9

answer

green leafy vegetables. Small reserve pool stored primarily in liver. Supplemental folic acid early in pregnancy reduces neural tube defects

question

function of vit B2/riboflavin

answer

cofactor in oxidation and reduction (FADH2). FAD and FMN are derived from riboflavin

question

Findings in vit B2 deficiency

answer

cheilosis, corneal vascularization

question

Function of vit b3/niacin

answer

constituent of NAD+, NADP+ (used in redox rxns), derived from tryptophan. Synth req vit B6.

question

Findings in deficiency of vit B3/niacin

answer

Glossitis. Severe deficiency leads to pellagra (can be caused by hartnup dz/decr tryptophan absorption), malignant carcinoid syndrome (incr tryptophan metabolism), and INH (decr vit B6). (Pellagra=diarrhea, dementia, dermatitis)

question

Findings in excess of vit B3/niacin

answer

facial flushing (2/2 pharmacologic doses for treatment of hyperlipidemia

question

Function of vitamin B5/pantothenate

answer

essential component of CoA (a cofactor for acyl transfers) and fatty acid synthase

question

Findings in deficiency of vit B5/pantothenate

answer

dermatitis, enteritis, alopecia, adrenal insufficiency

question

Function of vit B6/pyridoxine

answer

converted to pyridoxal phosphate, cofactor used in transamination(eg ALT and AST), decarboxylation rxns, glycogen phosphorylase. Synth of cystathionine, heme, niacin, histamine, and neurotransmitters incl serotonin, epinephrine, norepinephrine, and GABA

question

Findings in deficiency of vit B6/pyridoxine

answer

convulsions, hyperirritability, peripheral neuropathy (deficiency inducible by INH and ocps), sideroblastic anemias due to impaired hemoglobin synthesis and iron excess.

question

Causes of fat soluble vitamin deficiencies

answer

malabsorption syndromes(steratorrhea->cystic fibrosis, sprue) or mineral oil intake

question

Function of vitamin A/retinol

answer

antioxidant; constituent of visual pigments (retinal); essential for normal differentiation of epithelial cells into sepecialized tissue (pancreatic cells, mucus secreting cells); prevents squamous metaplasia. Used to treat measles and AML, subtype M3. found in liver and leafy vegetables

question

Findings in Vit A deficiency

answer

night blindness, dry skin

question

Findings in Vit A excess

answer

arthralgias, fatigue, headaches, skin changes, sore throat, alopecia. Teratogenic (cleft palate, cardiac abnormalities)->neg pregnancy test and reliable contraception needed before giving isotretinoin for severe acne

question

22q11 deletion syndromes

answer

variable presentation, including cleft palate, abnormal facies, thymic aplasia -> t cell deficiency. Cardiac defects, hypocalcemia 2ary to parathyroid aplasia, due to microdeletion at 22q11. Due to aberrant development of 3rd and 4th branchial pouches

question

DiGeorge syndrome

answer

thymic, parathyroid, and cardiac defects.

question

velocardofacial syndrome

answer

palate, facial, and cardiac defects

question

Williams syndrome

answer

congenital microdeletion of long arm of chromosome 7 (deleted region including elastin gene). Findings: distinctive "elfin" facies, intellectual disability, hypercalcemia (incr sensitivtiy to vit D), well developed verbal skills, extreme friendliness w/strangers, cardiovascular problems

question

Cri-du-Chat syndrome

answer

congenital microdeletion of short arm of chromosome 5 (46XX or XY, 5p-_) Findings: microcephaly, severe mental retardation, high pitched crying/mewing, epicanthal folds, cardiac abnormalities

question

Robertsonian Translocation

answer

Nonreciprocal chromosomal translocation that commonly involves chromosome pairs 13,14,15,21,and22. One of the most common types of translocations. Occurs when 2 acrocentric chromosomes fuse and the 2 short arms are lost. Balanced translocations normally do not cause any abnormal phenotype. Unbalanced translocation results in miscarriage, stillbirth, and chromosomal imbalance

question

Patau's syndrome (trisomy 13)

answer

severe mental retardation, rocker bottom feet, microphtalmia, microcephaly, cleft lip/palate, holoprosencephaly, polydactyly, cogenital heart dz. Death usually occurs w/in 1 year of birth. Results of 1st trimester pregnancy screen: decr free beta hCG, decr PAPP-A, and incr nuchal translucency

question

Edward's syndrome (trisomy 18)

answer

Findings: severe mental retardation, rocker bottom feet, micrognathia, low set ears, clenched hands, prominent occiput, congenital heart dz. Death usually occurs within one year of birth. Most common trisomy resulting in live birth after trisomy 21. results of pregnancy quad screen: decr alpha-fetoprotein, decr beta hCG, decr estriol, normal inhibin A

question

Findings in Down syndrome

answer

mental retardation, flat facies, prominent epicanthal folds, simian crease, gap b/w 1st 2 toes, duodenal atresia, congenital heart dz (most commonly ostium primum type ASD)

question

Late sequelae of Down syndrom

answer

Incr risk of ALL and Alzheimer's Dz (>35 yo)

question

Cause of Down syndrome

answer

95% of cases due to meiotic nondisjunction of homologous chromosomes (ass'd w/AMA), 4% of cases due to Robersonian translocation, 1% of cases due to Down mosaicism (no maternal ass'n)

question

Results of pregnancy quad screen in Down syndrome

answer

decr alpha-fetoprotein, incr beta-hCG, decr estriol, incr inhibin A. Ultrasound shows incr nuchal translucency in first trimester

question

Trinucleotide repeat expansion diseases

answer

1. Fragile X syndrome (CGG) 2. Friedreich's Ataxia (GAA) 3. huntington's disease (CAG) 4. myotonoic dystrophy (CTG). All may show genetic anticipation (disease severity incr and age of onset decr in successive generations)

question

Fragile X syndrome

answer

X-linked defect affecting the methylation and expression of the FMR1 gene. 2nd most common cause of genetic mental retardation. Findings: macroorchidism, long face w/large jaw, large everted ears, autism, mitral valve prolapse. CGG

question

Becker's muscular dystrophy

answer

X-linked mutated dystrophin gene. Less severe than Duchenne's/ onset in adolescene or early adulthood

question

Duchenne's muscular dystrophy

answer

Xlinked frameshift mutation-> deletion of dystrophin gene-> accelerated muscle breakdown. Weakness begins in pelvic girdle muscles and progresses superiorly. Pseudohypertrophy of calf muscles due to fibrofatty replacement of muscle. Gower's manuver. onset before 5 years of age.

question

Dystrophin gene

answer

DMD=longest known human gene-> incr rate of spontaneous mutation. Dystrophin helps anchor muscle fibers, primarily in skeletal and cardiac muscle.

question

Diagnosis of muscular dystrophy

answer

Incr CPK and muscle biopsy

question

X linked recessive disorders

answer

Bruton's agammaglobulinemia, Wiskott-Aldrich syndrome, Fabry dz, G6PD deficiency, ocular albinism, Lesch-nyhan syndrome, Duchennes and Beckers muscular dystrophy, Hunter's syndrome, Hemophilia A and B, Ornitihine transcarbamoylase deficiency. Female carriers may be affected and have less severe symptoms due to random x xsome inactivation in each cell.

question

Defect in cystic fibrosis

answer

Autosomal recessive defect in CFTR gene on chromosome 7, commonly deleton of Phe 508. CFTR channel actively secretes Cl- in lungs and GI tract and actively resorbs Cl- from sweat

question

Pathophysiology of cystic fibrosis

answer

defective cl- channel -> secretion of abnormally thick mucus that plugs lungs, pancreas, and liver -> recurrent pulm infections (Pseudomonas spp, S. aureus), chronic bronchitis, bronchiectasis, pancreatic insufficiency (malabsorption and steattorhea), nasal polyps, and meconium ileus in newborns. Mutation often causes abnormal protein folding resulting in degradation of channel before reaching cell surface.

question

Diagnosis of cystic fibrosis

answer

incr [] of Cl- ions in sweat test is diagnostic

question

Treatment of cystic fibrosis

answer

N-acetylcysteine to loosen mucus plugs (cleaves disulfide bonds w/in mucous glycoproteins)

question

Why are males w/CF infertile?

answer

bilateral absence of vas deferens

question

Autosomal recessive diseases

answer

albinism, ARPKD, cystic fibrosis, glycogen storage dzs, hemochromatosis, mucopolysaccharidoses (except Hunters), phenylketonuria, sickle cell, sphingolipidoses (exc Fabry's), thalassemas

question

von Hippel lindau dz

answer

Autosomal dominant. Hemangioblastomas of retina/cerebellum/medulla, majority of affected individuals develop multiple bilateral renal cell carcinomas and other tumors. Ass'd w/deletion of VHL gene (tumor suppressor) on chromosome 3 (3p). Results in constitutive expression of HIF (transcription factor) and activation of angiogenic growth factors

question

Tuberous sclerosis

answer

Autosomal dominant. Facial lesions (adenoma sebaceoum), hypopigmented (ash leaf spots) on skin, cortical, and retinal hamartomas, seizures, mental retardation, renal cysts, renal angiomyolipomas, cardiac rhabdomyomas, incr incidence of astrocytomas. Incomplete penetrance, variable presentation

question

Neurofibromatosis type 2

answer

Biilateral acoustic schwannomas, juvenile cataracts, NF2 gene on chromosome 22. Autosomal dominant

question

Neurofibromatosis type 1/von Recklinghausen's dz

answer

café-au-lait spots, neural tumors, Lisch nodules (pigmented iris hamartomas). Also marked by skeletal pathologies (scoliosis) and optic pathway gliomas. On long arm of xsome 17. Autosomal dominant

question

Multiple endocrine neoplasias

answer

autosomal dominant. Several distinct syndromes.

question

Marfan's syndrome

answer

autosomal dominant. Fibrillin-1 gene mutation -> connective tissue disorder affecting skeleton, heart, and eyes. Tall w/long extremities, pectus excavatum, hypermobile joints, long tapering fingers and toes (arachnodactyly). Cystic medial necrosis of aorta->aortic incompetence and dissecting aortic aneurysmsl floppy mitral valve. subluxation of lenses

question

Huntingtons disease

answer

autosomal dominant. Depression, progressive dementia, choreiform movements, caudate atrophy, decr levels of GABA and decr ACh in brain. Symptoms manifest b/w ages of 20-50. gene located on chromosome 4. trinucleotide repeat disorder (CAG)

question

Hereditary spherocytosis

answer

autosomal dominant.spheroid erythrocytes due to spectrin or ankyrin defect; hemolytic anemia, incr MCH. Splenectomy is curative

question

Hereditary hemorrhagic telangiectasia (Osler-weber-rendu)

answer

autosomal dominant.inherited disorder of blood vessels. Findings: telangiectasia, recurrent epistaxis, skin discolorations, arteriovenous malformations

question

Familial hypercholesterolemia (hyperlipidemia type IIA)

answer

autosomal dominant. elevated LDL due to defective or absent LDL receptor. Heterozygotes have cholesterol ~200. Homozygotes (rare) have cholesterol ~700. severe atherosclerotic dz early in life. Tendon xanthomas (classically achilles). MI may develop before age 20

question

Familial adenomatous polyposis

answer

Autosomal dominant. Colon becomes covered w/adenomatous polyps after puberty. Progresses to colon cancer unless colon is resected. Mutations on chromosome 5 (APC gene)

question

Autosomal dominant polycystic kidney disease

answer

adult. Always bilateral massive enlargement of kidneys due to multiple large cysts. Presents w/flank pain, hematuria, htn, progressive renal failure. 85% of cases are due to mutation in PKD1 on chromosome 16. ass'd w./polycystic liver dz, berry aneurysms, mitral valve prolapse. infantile form is recessive

question

achondroplasia

answer

autosomal dominant. Cell-signaling defect of fibroblast growth factor (FGF) receptor 3. results in dwarfism, short limbs, larger head but trunk size is normal. Ass'd w/advanced paternal age

question

mItochrondial myopathies

answer

group of rare disorders resulting from mutations affecting mitochondrial function. Often present w/myopathy and CNS dz. Muscle biopsy often shows "ragged red fibers"

question

Mitochondrial inheritance

answer

trasmitted only through mother. All offspring of affected females may show dz. Often due to failures in oxidative phosphorylation. Variable expression in pop'n due to heteroplasmy

question

Xlinked dominant

answer

transmitted through both parents. Either male or female offspring of the affected mother may be affected; all female offspring of affected father are affected

question

Hypophosphatemic rickets

answer

aka vitamin D resistant rickets. Inherited disorder resulting in incr phosphate wasting at proximal tubule

question

xlinked recessive

answer

sons of heterozygous mothers have a 50% chance of being affected. No male-to-male transmission. Females usually must be homozygous to be affected

question

Autosomal recessive

answer

25% of offspring from 2 carrier parents are affected. Often due to enzyme deficiencies. Usually seen in only 1 generation. Commonly more severe than dominant disorders. Likely present in childhood

question

Autosomal dominant

answer

often due to defects in structural genes. Many generations, both male and female, affected. Often pleiotropic. Family history crucial to diagnosis

question

Angelman's syndrom

answer

Maternal allele is not expressed. Mental retardation, seizures, ataxia, inappropriate laughter

question

Prader-Willi syndrome

answer

Paternal allele is not expressed. Mental retardation, hyperphagia, obesity, hypogonadism, hypotonia

question

Imprinting

answer

At some loci only 1 allele is active, the other is inactive (imprinted/inactivated by methylation). With 1 allele inactivated, deletion of the active allele -> disease. Both prader-willi and angelman's sydnromes due to inactivation or deletion of genes on chromosome 15. can also occur as a result of uniparental disomy

question

Hardy-Weinberg Law assumptions

answer

1. No mutation occurring at the locus 2. No selection for any of the geneotypes at the locus 3. Completely random mating 4. No net migration

question

Hardy-Weinberg pop'n genetics

answer

p^2+2pq+q^2=1; p+q=1. Frequency of an xlinked recessive disease in males=q and in females=q^2

question

Uniparental disomy

answer

offspring receives 2 copies of a chromosome from 1 parent and no copies from the other parent. Heterodisomy indicates a meiosis I error; Isodisomy indicates a meiosis II error or postzygotic chromosomal duplication of one of a pair of chromosomes, and loss of the original pair. Most occurrences of UPD->normal phenotype. Consider UPD in an individual manifesting a recessive disorder when only one parent is a carrier.

question

Heteroplasmy

answer

presence of both normal and mutated mtDNA, results in variable expression of mitochondrially inherited dz

question

Locus heterogeneity

answer

Mutations at dif't loci can produce the same phenotype. Marfan's syndrome, MEN2B, and homocystinuria all cause marfanoid habitus. Albinism

question

Mosaicism

answer

occurs when cells in the body differ in genetic makeup due to postfertilization loss or change of genetic info during mitosis. Can be a germ-line mosaic (gonadal mosaicism) which may cause a dz not carried by a parent's somatic cells.

question

Chimeric individual

answer

Formed from 2 individual zygotes that subsequently fuse

question

Linkage disequilibrium

answer

Tendency for certain alleles at 2 linked loci to occur together more often than expected by chance. Measured in a pop'n, not in a family, and often varies in dif't pop'ns

question

Dominant negative mutation

answer

exerts a dominat effect. Heterozygote produces a nonfunctional altered protein that also prevents the normal gene product from functioning. Ex: mutation of a transcription factor in an allosteric site. Nonfunctioning mutant can still bind DNA preventing normal wild type transcription factor from binding

question

Loss of heterozygosity

answer

if a pt inherits or develops a mutation in a tumor supressor gene, the complementary allele must be deleted/mutate before cancer develops. NOT true of oncogenes. Ex: retinoblastoma and "two-hit" hypothesis

question

Anticipation

answer

Increased severity or earlier onset of disease in succeeding generations. Ex: huntingtons

question

Pleiotropy

answer

one gene contributes to multiple phenotypic effects. Ex: pku causes many seemingly unrelated symptoms: mental retardation to hair/skin changes

question

Incomplete penetrance

answer

not all individuals w/a mutant genotype show the mutant phenotype. BRCA1 gene mutations do not always result in breast/ovarian cancer

question

Variable expressivity

answer

Phenotype varies among individuals w/same genotype. 2 pts w/neurofibromatosis type I may have varying dz severity

question

Codominance

answer

both alleles contribute to the phenotype of the heterozygote. Blood groups

question

karyotyping

answer

process in which metaphase chromosomes are stained, ordered, and numbered according to morphology, size, arm-length ratio, and banding pattern. Can be performed on a sample of blood, bone marrow, amniotic fluid, or placental tissue. Used to diagnose chromosomal imbalances (trisomies, sex chromosome disorders)

question

Gene expression modifications

answer

transgenic strategies in mice: 1.random insertion of gene into mouse genome 2. targeted insertion or deletion of gene through homologous recombination w/mouse gene

question

Cre-lox system

answer

Can inducibly manipulate genes at specific developmental points using an antibiotic controlled promoter (eg to study a gene whose deletion causes embryonic deletion)

question

RNA interference

answer

RNAi. dsRNA is synthesized that is complementary to the mRNA sequence of interest. When transferred into human cells, dsRNA separates and promotes degradation of targe mRNA, knocking down gene expression

question

Cloning methods

answer

Cloning=production of recombinant DNA molecule that is self perpetuating. 1. Isolate eukaryotic mRNA (post-RNA processing steps) of interest 2. Expose mRNA to reverse transcriptase to produce DNA 3. Insert cDNA fragments into bacterial plasmid containing antibiotic resistance genes 4. surviving bacteria on antibiotic medium produces cDNA library.

question

Fluorescence in situ hybridization (FISH)

answer

Fluorescent DNA or RNA probe binds to specific gene site of interest on chromosomes. Used for specific localization of genes and direct visualization of anomalies (e.g. microdeletions) at molecular level (when deletion is too small to be visualized by karyotype). Fluorescence=gene is present, No fluorescence=gene has been deleted

question

Enzyme linked immunoabsorbent assay

answer

Rapid immunologic technique testing for antigen-antibody reactivity. Both sensitivity and specificity approach 100%

question

Indirect ELISA

answer

uses a test antigen to see if a specific antibody is present in the patient's blood; 2ary antibody copied to a color generating enzyme. If target is present in sample, sol'n will have an intense color

question

Direct ELISA

answer

uses a test antibody coupled to a color generating enzyme see if a specific antigen is present in a patient's blood

question

Microarrays

answer

thousands of nucleic acid sequences are arranged in grids on glass or silicon. DNA or RNA probes are hybridized to the chip and an scanner detects relative amounts of complementary binding. Used to profile gene expression levels of thousands of genes simultaneously. abile to detect SNPs

question

Southwestern blot

answer

idnetifies DNA-binding proteins (eg transcription factors) using labeled oligonucleotide probes

question

Western blot

answer

Sample proetin is separated via gel electrophoresis and transferred to filter. Labeled antibody used to bind to relevant protein

question

Northern blot

answer

similar to southern blot except that an RNA sample is electrophoresed. Useful for studying mRNA levels

question

Southern blot

answer

SNA sample Is electrophoresed on a gel and then transferred to a filter. Soaked in denaturent and subseq exposed to a radiolabeled DNA probe that recognizes and anneals to its complementary strand. Resulting double-stranded, labeled piece of DNA is visualized when filter is exposed to film

question

Steps of polymerase chain reaction

answer

1. Denaturation-DNA is denatured by heating to generate 2 separate strands 2. Annealing-during cooling, excess premade DNA primers anneal to a specific sequence on each strand to be amplified 3. elongation-heat stable DNA polymerase replicates the DNA sequence following each primer. Steps are repeated multiple times for DNA sequence amplification. agarose gel electrophoresis-used for size separation of PCR products (smaller molecules travel farther) compared against a DNA ladder

question

Elastin

answer

stretchy protein w/in skin, lungs, large areteries, elatic ligaments, vocal cord, ligamenta flava (connect vertebrae->relaxed and stretched conformations). Rich in proline and glycine, nonhydroxylated forms. Tropoelastin w/fibrillin scaffolding. Crosslinking takes place extracellulary and gives elastin its elastic properties. broken down by elastase which is normally inhibited by alpha-1-antitrypsin

question

Alport syndrome

answer

due to a variety of gene defects resulting in abnormal type IV collagen. Most common form is xlinked recessive. Characterized by progressive hereditary nephritis and deafness. May be ass'd w/ocular disteurbances. Type iV collagen =important component of basement membrane of kidney, ears, and eyes

question

Ehlers-Danos syndrome

answer

Faulty collagen synth causing hyperextensible skin, tendencyto bleed (easy bruising), and hypermobile joints. 6 types: severity and inheritance vary. Can be autosomal dominant or receissive. May be ass'd w.joint dislocations, berry aneurysms, organ rupture. Type I or Type V collagen most freq affected in severe classic Ehlers-Danlos syndrome

question

Osteogenesis imperfecta

answer

Caused by a variety of genetic defects-most common=autosomal dominant. Abnormal type I collagen causes: 1.multiple fractures w/minimal trauma. May occur during birth process 2.blue sclerae due to translucency of connective tissue over choroidal veins 3. hearing loss (abnormal middle ear bones) 4.dental imperfections due to lack of dentin. NOTE-may be confused w/child abuse

question

Synthesis of collagen.

answer

Inside fibroblasts-rough endoplasmic reticulum. Translation of collagen alpha chains (precollagen)-usually Gly-X-Y. (X and Y are proline or lysine)

question

hydroxylation of collagen

answer

In endoplasmic reticulum of fibroblast. hydroxylation of specific proline and lysine residues (requires vit C->deficiency->scurvy)

question

Glycosylation of collagen

answer

in endoplasmic retiuclum of fibroblast. Glycosylation of pro-alpha-chain hydroxylysine residues and formation of procollagen via hydrogen and disulfide bonds (triple helix of 3 collagen alpha chains). Problems forming triple helix=osteogenesis imperfecta

question

Exocytosis of collagen

answer

exocytosis of procollagen from fibroblast into extracellular space

question

Proteolytic processing of collagen

answer

Cleavage of disulfide rich terminal regions of procollagen transforming it into insoluble tropocollagen. Takes place outside of fibroblast

question

Cross-linking of collagen

answer

reinforcement of many staggered tropocollagen molecules by covalent lysine-hydroxylysine cross linkage (by Cu2+ containing lysyl oxidase) to make collagen fibrils. Problems w/crosslinking=Ehlers Danlos

question

Collagen

answer

most abundant protein in the human body. Extensively modified by posttranslational modification. Organizes and strengthens extracellular matrix.

question

Type I collagen

answer

most common (90%). Bone, skin, tendon, dentin, fascia, cornea, late wound repair. Defective in osteogenesis imperfecta

question

type II collagen

answer

cartilage (including hyaline), vitreous body, nucleus pulposus

question

Type III collagen

answer

reticulin. Skin, blood vessels, uterus, fetal tissue, granulation tissue. Defective in ehlers danlos

question

type IV collagen

answer

basement membrane or basal lamina. Defective in alport syndrome

question

Sodium-potassium pump

answer

Na+K+ATPase located in plasma membrane w/ATP site on cytosolic side. For each ATP consumed, 3Na+ go out, 2K+ come in. During cycle, pump is phosphorylated. Ouabain inhibits by binding to K+ site. Cardiac glycosides (digoxin and digitoxin) directly inhibit Na+ K+ ATPase which leads to indirect inhibition of Na+/Ca2+ exchange->incr Ca2+ concentration ->incr cardiac contractility

question

Cell type stained by neurofilaments

answer

neurons

question

cell type stained by GFAP

answer

neuroglia

question

cell type stained by cytokeratin

answer

epithelial cells

question

cell type stained by desmin

answer

muscle

question

cell type stained by vimentin

answer

connective tissue

question

plasma membrane composition

answer

asymmetric lipid bilayer. Contains cholesterol, phospholipids, sphingolipids, glycolipids, and proteins

question

Intermediate filaments

answer

cytoskelatal element resp for structure.vimentin, desmin, cytokeratin, lamins, glial fibrillary acid proteins (GFAP)

question

Microtubule

answer

cytoskeletal element responsible for movement. Cilia, flagella, mitotic spindle, axonal trafficking, centrioles

question

Actin and myosin

answer

cytoskeletal element. Microvilli, muscle contraction, cytokinesis, adherens junctions

question

Cilia structure

answer

9+2 arrangement of microtubules. Axonemal dynein-ATPase that links peripheral 9 doublets and causes bending of cilium by differential sliding of doublets

question

Kartageners syndrome aka primary ciliary dyskinesia

answer

immotile cilia due to a dynein arm defect. Results in male infertility (immotile sperm) and decr female infertility, bronchiectasis, and recurrent sinusitis (bacteria and particles not pushed out) ,ass'd with situs inversus

question

Structure of microtubule

answer

cylindrical structure composed of a helical array of polymerized dimers of alpha- and beta- tubulin. Each dimer has 2 GTP bound. Incorporated into flagella, cilia, mitotic spindles. Grows slowly, collapses quickly. Also involved in slow axoplasmic transport in neurons.

question

Molecular motor proteins

answer

transport cellular cargo toward opposite ends of microtubule tracks. Dynein=retrograde to microtubule (+ -> -) Kinesin=anterograde to microtubule (- ->+)

question

Drugs that act on microtubules

answer

mebendazole/thiabendazole (antihelminthic), griseofulvin (antifungal), vincristine/vinblastine (anti-cancer), paclitaxel (anti-breast cancer), colchicine (anti-gout)

question

Chediak-Higashi syndrome

answer

mutation in the lysosomal trafficing regulator gene (LYST) whose product is req'd for the microtubule dependent sorting of endosomal proteins into late multivesicular endosomes. Results in recurrent pyogenic infections, partial albinism, peripheral neuropathy

question

Proteasome

answer

barrel-shaped protein complex that degrades damaged or unnecc proteins tagged for destruction with ubiquitin

question

peroxisome

answer

membrane-enclosed organelle involved in catabolism of very long fatty acids and amino acids

question

I-cell disease aka inclusion cell disease

answer

inherited lysosomal storage disorder, failure of addition of mannose-6-phosphate to lysosome proteins (enzymes are secreted outside the cell instead of being targeted to the lysosome) results in coarse facial features, clouded corneas, restricted joint movement, and high plasma levels of lysosomal enzymes. often fatal in childhood

question

Vesicular trafficking proteins

answer

1. COPI: Golgi->Golgi (retrograde); Golgi->ER 2. COPII: Golgi->Golgi (anterograde); ER->Gogli 3. Clathrin: trans-Golgi->lysosomes; plasma membrane->endosomes (receptor mediated endocytosis)

question

Cell trafficking

answer

golgi=distribution center for proteins and lipids from the ER to the vesicles and plasma membrane. Modifies N-oligosaccharides on asparagine. Adds O-oligosaccharides on serine and threonine. Adds mannose-6-phosphate to proteins for trafficking to lysosomes. endosomes are sorting centers for material from outside the cell or from the Golgi, sending it to lysosomes for destruction or back to the membrane/Golgi for further use

question

smooth endoplasmic retiuclum

answer

site of steroid synthesis and detox of drugs and poisons. Liver hepatocytes and steroid hormone producing cells of the adrenal cortex are rich in SER

question

Rough endoplasmic reticulum

answer

site of synth of secretory (exported) proteins and of N linked oligosaccharide add'n to many proteins. Mucus secreting goblet cells of the small intestine and antibody secreting plasma cells are rich in RER

question

Nissl bodies

answer

(=RER in neurons). Synthesize enzymes (eg ChAT aka choline acetyltransferase makes ACh) and peptide neurotransmitters.

question

Free ribosomes

answer

unattached to any membrane, site of synth of cytosolic and organellar proteins

question

Labile cell types

answer

never go to G0, divide rapidly w/a short G1. Bone marrow, gut epithelium, skin, hair follicles, germ cells

question

Stable (quiescent) cell types

answer

Enter G1 from G0 when stimulated. Hepatocytes, lymphocytes

question

Permanent cell types

answer

remain in G0, regenerate from stem cells. Neurons, cardiac and skeletal muscle, RBCs

question

Tumor suppressors

answer

p53 and hypophosphorylated Rb normally inhibit G1-to-S progression; mutations in these genes result in unrestrained cell division

question

Cyclin-CDK complexes

answer

must be both activated and inactivated for cell cycle to progress

question

cyclins

answer

regulatory proteins that control cell cycle events; phase specific, activate CDKs

question

CDKs

answer

cyclin-dependent kinases; constitutive and inactive

question

Cell cycle phases

answer

checkpoints control transitions b/w phases of cell cycle. This process is regulated by cyclins, CDKs, and tumor suppressors. Mitosis (shortest phase): prophase-metaphase-anaphase-telophase. G1 and G0 of variable duration

question

Proteosomal degradation

answer

Post-translational modification. Attachment of ubiquitin to defective proteins to tag them for breakdown

question

Covalent alterations

answer

Post translational modifications. Phosphorylation, glycosylation, hydroxylation, methylation, and acetylation

question

Trimming

answer

post translatonal modification. Removal of n- or c- terminal propeptides from zymogens to generate mature proteins

question

Initiation of protein synthesis

answer

Activated by GTP hydrolysis, initiation factors (eukaryotic Ifs) help assemble the 40S ribosomal subunit with the initiator tRNA and are released when the mRNA and the ribosomal subunit assemble with the complex. ATP-tRNA activation. GTP-tRNA translocation. Eukaryotes:40S+60S->80S. Prokaryotes: 30S+50S->70S

question

Elongation (protein synthesis)

answer

1. Aminoacyl tRNA binds to A site (except for initiator methionine) 2. Ribosomal rRNA (ribozyme) catalyzes peptide bond formation, transfers growing polypeptide to amino acid in A site 3. Ribosome advances 3 nucleotides toward 3' end of mRNA, moving peptidyl tRNA to P site (translocation)

question

Termination (protein synthesis)

answer

stop codon is recognized by release factor, and completed protein is released from ribosome

question

Antibiotics that act as protein synthesis inhibitors

answer

1. Aminoglycosides-bind 30S + inhibit formation of initiation complex->cause misreading of mRNA. 2. Tetracyclines bind 30S + block aminoacyl tRNA from entering the acceptor site 3. Chloramphenicol binds 50S and inhibits peptidyl transferase 4. Macrolides bind 50S + prevent release of uncharged tRNA after it has donated its amino acid

question

tRNA wobble

answer

Accurate base pairing is req'd only in 1st 2 nucleotide positions of an mRNA codon so codons differing in the 3rd "wobble" position may code for the same tRNA/amino acid ( as a result of degeneracy of genetic code)

question

Charging of tRNA

answer

aminoacyl-tRNA synthetase (1 per amino acid "matchmaker"uses ATP) scrutinizes amino acid before and after it binds to tRNA. If incorrect, bond is hydrolyzed. Amino acid-tRNA bond has energy for formationof peptide bond. Mischarged tRNA reads usual codon but inserts wrong amino acid. Aminoacyl tRNA synthetase + binding of charged tRNA to the codon are responsible for accuracy of amino acid selection. Tetracyclines bind to 30S subunit, preventing aminoacyl-tRNA.

question

Structure of tRNA

answer

75-90 nucleotides, 2ary structure, cloverleaf form, anticodon end is opposite. 3' aminoacyl end. All tRNAs, both eukaryotic and prokaryotic, have CCA at 3' end along w/a high percentage of chemically modified bases. The amino acid is covalently bound to the 3' end of the tRNA

question

Introns

answer

intervening noncoding segments of DNA

question

Exons

answer

contain the actual genetic info coding for protein. Dif't exons can be combined by alternative splicing to make unique proteins in dif't tissues (eg beta-thal mutations)

question

Splicing of pre-mRNA

answer

1. 1ary transcript combines w/snRNPs and other proteins to form spliceosome. 2. Lariat shaped (looped) intermediate is generated. 3. Lariat is released to remove intron precisely and join 2 exons. Pts w/lupus make Abs to spliceosomal snRNPS

question

RNA processing (eukaryotes)

answer

Initial transcript=heterogenous nuclear RNA (hnRNA). hnRNA destined for translation=pre-mRNA. Processing occurs in nucleus. After transcription: capping on 5'end (add'n of 7-methylguanosine cap), polyadenylation on 3' end (=200As), splicing out of introns. capped, tailed, and spliced transcript is called mRNA. Only processed RNA is transported out of nucleus. Poly-A polymerase does not require a template. AAUAAA=polyadenylation signal

question

Prokaryote RNA polymerase

answer

1 RNA polymerase (multisubunit complex) makes all 3 kinds of RNA

question

RNA polymerase I

answer

makes rRNA (most numerous RNA)

question

RNA polymerase II

answer

makes mRNA (largest RNA). No proofreading function but can initiate chains. RNA polymerase II opens DNA at promoter site.

question

RNA polymerase III

answer

makes tRNA (smallest RNA)

question

alpha-amantin

answer

found in Amanita phalloides (death cap mushrooms) inhibits RNA polymerase II. Causes severe hepatotoxicity if ingested.

question

Silencer (gene expression)

answer

site where negative regulators (repressors) bind

question

Enhancer (gene expression)

answer

stretch of DNA that alters gene expression by binding transcription factors. Enhancers and silencers may be located close to, far from, or even within (in an intron) the gene whose expression it regulates.

question

Promoter (gene expression)

answer

site where RNA polymerase and multiple other transcription factors bid to DNA upstream from gene locus (AT-rich upstream sequence with TATA and CAAT boxes). Promoter mutation commonly results in dramatic decr in amount of gene transcribed

question

mRNA stop codons

answer

UGA, UAA, UAG

question

mRNA start codons

answer

AUG (rarely GUG)

question

Eukaryote mRNA start codons

answer

codes for methionine which may be removed before translation is completed

question

Prokaryote mRNA start codons

answer

Codes for formylmethionine (f-met)

question

DNA/RNA/protein sytnthesis direction

answer

DNA and RNA are both synthesized 5'->3'. 5' of incoming nucleotide bears the triphosphate (energy source for bond). Triphosphate bond=target of 3'hydroxyl attack. Drugs blocking DNA replication often have modified 3'OH, preventing add'n of next nucleotide ("chain termination") mRNA is read 5' to 3'. Protein synth is N-terminus to C-terminus

question

Nonhomologous end joining

answer

Binds together 2 ends of DNA fragments to repair double stranded breaks. No req for homology. Mutated in ataxia telangiectasia

question

Mismatch repair

answer

Newly synth stand is recognized, mismatached nucleotides are removed and gap is filled and resealed. Mutated In hereditary nonpolyposis colorectal cancer

question

Bae excision repair

answer

Specific glycosylases recognize and remove damaged bases, apurinic/apyriminidic endonuclease cuts DNA at both apurinic and pyrimidinic sites, empty sugar is removed, and gap is filled and resealed. Important in repair of spontaneous/toxic deamination

question

Nucleotide excision repair

answer

Specific endonucleases release the oligonucleotide-containing damaged bases, DNA polymerase and ligase fill and reseal the gap, respectively. Repairs bulky helix-distorting lesions. Mutated in xeroderma pigmentosum, which prevents repair of pyrimidine dimers b/c of UV light exposure

question

telomerase

answer

enzyme adds DNA to 3' end of chromosomes to avoid loss of genetic material w/every duplication

question

DNA ligase

answer

catalyzes the formation of phosphodiesterase bond w/in a strand of dsDNA (ie joins Okazaki fragment). Seals

question

DNA polymerase I

answer

prokaryotic only. Degrades RNA primer, replaces it with DNA. Has same functions as DNA polymerase III but also excises RNA primer with 5'->3' exonuclease

question

DNA polymerase III

answer

prokaryotic only. Elongates leading strand by adding deoxynucleotides to the 3' end. Elongates lagging strand until it reaches primer of preceding fragment 3'->5' exonuclease activity "proofreads" each added nucleotide. DNA polymerase III has 5'->3' synthesis and proofreads w/ 3'->5' exonuclease

question

Primase

answer

makes an RNA primer on which DNA polymerase III can initiate replication.

question

DNA topoisomerases

answer

create a nick in the helix to relieve supercoils created during replication. Fluoroquinolones inhibit DNA gyrase (prokaryotic topoisomerase II)

question

Single stranded binding proteins

answer

prevent strands from reannealing

question

helicase

answer

unwinds DNA template at replication fork

question

replication fork

answer

Y shaped region along DNA template where leading and lagging strands are synthesized

question

Origin of replication

answer

particular consensus sequence of base pairs in genome where DNA replication begins. May be single (prokaryotes) or multiple (eukaryotes)

question

DNA replication

answer

eukaryotic DNA replication is more complex than prokaryotic process but uses many enzymes analagous. In both prokaryotes and eukaryotes, DNA replication is semiconservative and involves both continuous and discontinuous (Okazaki fragment) synthesis

question

Frameshift mutation

answer

change resulting in misreading of all nucleotides downstream, usually resulting in a truncated, nonfunctional protein

question

Nonsense mutation

answer

change resulting in early stop codon

question

Missense mutation

answer

changed amino acid (conservative-new amino acid is similar in chemical structure)

question

Silent mutation

answer

same amino acid, often base change in 3rd position of codon (tRNA wobble)

question

Severity of point mutations in DNA

answer

silent<missense<nonsense<frameshift

question

Universal genetic code

answer

genetic code is conserved throughout evolution. Exception in humans=mitochondria

question

Commaless, nonoverlapping genetic code

answer

read from a fixed starting point as a continuous sequence of bases. Exceptions=some viruses.

question

Degenerate/redundant genetic code

answer

most amino acids are coded by multiple codon. Exceptions=methionine and tryptophan encoded by only 1 codon (AUG and UGG respectively)

question

unambiguous genetic code

answer

each codon specifies only 1 amino acid

question

Lesch-Nyhan syndrome

answer

defective purine salvage owing to absence of HGPRT which converts hypoxanthine to IMP and guanine to GMP. Results in excess uric acid production and deNovo purine synthesis. Xlinked recessive. Findings=retardation, self-mutilation, aggression, hyperuricemia, gout, choreoathetosis

question

Adenosine deaminase deficiency

answer

Excess ATP and dATP imbalances nucleotide pool via feedback inhibition of ribonucleotide reductase->prevents DNA synth and decr lymphocyte count. One of the major causes of SCID. Autosomal recessive. 1st dz to be treated by experimental human gene therapy

question

orotic aciduria

answer

inability to convert orotic acid to UMP (de novo pyrimidine synth pathway) b/c of defect in UMP synthase (a bifunctional enzyme). Autosomal recessive

question

Findings in orotic aciduria

answer

incr orotic acid in urine, megaloblastic anemia (does not improve w/vit B12 or folic acid), failure to thrive. No hyperammonemia (vs OTC deficiency which has incr orotic acid w/hyperammonemia)

question

Treatment of orotic aciduria

answer

oral uridine administration

question

Antineoplastic and antibiotic drugs that function by interfering w/purine synthesis

answer

1. Hydroxyurea-inhibits ribonucleotide reductase 2. 6-mercaptopurine blocks de novo purine synth 3. 5-fluorouracil inhibits thymidylate synthase (decr deoxythymidine monophosphate aka dTMP) 4. Methotrexate (MTX) inhibits dihydrofolate reductase (decr dTMP) 5. Trimethoprim inhibits bacterial dihydrofolate reductase (decr dTMP)

question

Nucleotides

answer

purines (A,G)-2 rings. Pyrimidines (C,T,U) 1 ring. Guanine has a ketone. Thymine has a methyl. Deamination of cytosine makes uracil. Uracil found in RNA, thymine in DNA. G-C bond (3H bonds) stronger than A-T bond ( 2Hbonds). Incr G-C content->incr melting temp

question

Amino acids necc for purine synthesis

answer

glycine, aspartate, glutamine

question

Nucleoside

answer

base+ribose (sugar)

question

Nucleotide

answer

base + ribose + phosphate linked by 3'-5' phosphodiester bond

question

Histone acetylation

answer

relaxes DNA coiling, allowing for transcription. Acetylation makes DNA active

question

Histone methylation

answer

inactivates transcription of DNA (makes DNA mute)

question

DNA methylation

answer

template strand cytosine and adenine are methylated in DNA replication which allows mismatch repair enzymes to distinguish b.w old and new strands in prokaryotes

question

Euchromatin

answer

less condensed, transcriptionally active, sterically accessible. Eu[=truly transcribed

question

Heterochromatin

answer

condensed, transcriptionally inactive, sterically inaccesseble. Highly condensed

question

Chromatin structure

answer

DNA exists in the condensed, chromatin form to fit into the nucleus. Negatively charged DNA loops twice around positively charged histone octamer to form nucleosome "bead". Histones are rich in the amino acids lysine and arginine. H1 ties nucleosome beads together in a string. In mitosis, DNA condenses to form chromosomes. H1 is only histone that is not in the nucleosome core

question

Aspartate transcarbamoylase (ATCase)

answer

What is the rate limiting step of de novo pyrimidine synthesis

question

Glutamine-PRPP amidotransferase

answer

What is the rate limiting step of de novo purine synthesis

question

Phosphofructokinase-1 (PFK-1)

answer

What is the rate limiting step of glycolysis

question

Fructose-1,6-bisphosphatase (F-1,6-BP)

answer

What is the rate limiting step of gluconeogenesis

question

Isocitrate dehydrogenase

answer

What is the rate limiting step of the TCA cycle

question

Glycogen synthase

answer

What is the rate limiting step of glycogen synthesis

question

Glycogen phosphorylase

answer

What is the rate limiting step of glycogenolysis

question

Glucose-6-phosphate dehydrogenase (G6PD)

answer

What is the rate limiting step of the HMP shunt

question

Acetyl-CoA carboxylase (ACC, sytrate=synthesis, uses citrate shuttle)

answer

What is the rate limiting step of fatty acid synthesis

question

Carnitine acyltransferase I (carnage, uses carnitine shuttle)

answer

What is the rate limiting step of fatty acid oxidation

question

HMG-CoA synthase

answer

What is the rate limiting step of ketogenesis

question

HMG-CoA reductase (inhibited by statins)

answer

What is the rate limiting step of cholesterol synthesis

question

ALA synthase

answer

What is the rate limiting step of Heme synthesis

question

Carbamoyl phosphate synthase I

answer

What is the rate limiting step of the urea cycle

question

32 (heart and liver, malate-aspartate shuttle) or 30 (muscle, glycerol-3-phosphate shuttle)

answer

ATP produced by aerobic metabolism

question

"makes DNA Mute"

answer

CpG methylation

question

"CUT the Py" and "PURe As Gold"

answer

Purines/2rings = AG Pyrimidines = CUT (THYmine has a meTHYl)

question

"GAG"

answer

aa's necessary for purine synthesis: Glycine, Aspartate, Glutamine (+THF)

question

"Egyptians were very orotic"

answer

Orotic acid necessary for pyrimidine synthesis

question

MOA: ribavirin and Mycophenolate

answer

IMP dehydrogenase (Purines)

question

MOA: Hydroxyurea

answer

ribonucleotide reductase (pyrimidines)

question

MOA: 6-MP

answer

inhibit de novo purine synthesis

question

MOA: 5-FU

answer

Inhibit thymidylate synthase (pyrimidines)

question

MOA: MTX, TMP, Pyrimethamine

answer

Inhibit dihydrofolate reductase (humans, bacteria, and protozoa; pyrimidines)

question

MOA: Leflunomide

answer

Inhibit dihydroorotate dehydrogenase (pyrimidines)

question

"HGPRT", Lesch-Nyhan syndrome *X-linked recessive

answer

(Purine salvage deficiency) Hyperuricemia Gout Pissed off (Aggression, self-mutilation) Retardation dysTonia

question

One of the major causes of SCID

answer

ADA (adenosine deaminase deficiency) *Excess ATP→ feedback inhibition ribonucleotide reductase → ↓ DNA synthesis and ↓lymphocytes

question

MOA: Fluoroquinolones

answer

inhibit DNA gyrase (prokaryotic topoisomerase II)

question

Genetic defect: Xeroderma pigmentosum

answer

Nucleotide excision repair (i.e. pyrimidine dimers from UV)

question

Genetic defect: HNPCC (hereditary nonpolyposis colorectal cancer)

answer

Mismatch repair

question

Genetic defect: Ataxia telangiectasia

answer

Brings 2 DNA fragment ends together (i.e. double stranded breaks)

question

mRNA stop codons

answer

UGA: U Go Away UAA: U Are Away UAG: U Are Gone

question

MOA: alpha-amanitin

answer

inhibits RNA pol II (mRNA synthesis); heptatotoxicity

question

AAUAAA

answer

Poly-adenylation signal (3' tail of mRNA)

question

Anti-Smith antibodies

answer

antibodies to spliceosomal snRNPs *Specific for SLE

question

Anti-U1 RNP antibodies

answer

(RNP = ribonucleoproteins) *Associated with mixed connective tissue disease

question

"Can Carry Amino acids"

answer

At 3' end of tRNA (CCA); covalently bound aa

question

"Eukaryotes are Even", "prOkaryotes are Odd"

answer

Ribosomes Eukaryotes: 40S + 60S → 80S prOkaryotes: 30S + 50S → 70S

question

Li-Fraumeni Syndrome

answer

mutation in p53 and Rb; uncontrolled cell growth (G1 → S)

question

I-Cell Disease

answer

Defect in phosphotransferase → Golgi cannot phosphorylate mannose residues → ↓mannose-6-phosphate →proteins excreted, not trafficked to lysosomes *Coarse facies, clouded corneas, restricted joint movement

question

Signal Recognition Particle

answer

RNP; trafficks proteins from cytosol → RER

question

Peroxisome

answer

Catabolism of very long chain fatty acids; branched chain fatty acids; amino acids

question

Parkinson dx theory

answer

defect in ubiquitin-proteasome system

question

"Micotubules Get Constructed Very Poorly"

answer

Mebendazole (anti-heminth) Griseofulvin (anti-fungal) Colchicine (anti-gout) Vincristine/Vinblastine (anti-cancer) Paclitaxel (anti-cancer)

question

Molecular Motor Proteins

answer

Dynein (retrograde) Kinesin (anterograde)

question

Kartagener syndrome

answer

primary ciliary dyskinesia: dynein defect *infertility, bronchiectasis, sinusitis, situs inversus

question

Stains: 1. ViMENTin 2. DesMin 3. Cytokeratin 4. Gfap 5. Neurofilaments

answer

1. Vimentin - Connective tissue ('meant' to be together) 2. DesMin - Muscle 3. Cytokeratin - Epithelial 4. Gfap - neuroGlia 5. Neurofilaments - neurons

question

MOA: Cardiac glycosides (digoxin and digitoxin) and Ouabain

answer

direct inhibition of Na/K ATPase → ↑Ca → ↑contractility binds to K site of Na/K pump

question

"Be (So Totally) Cool, Read Books"

answer

Collagen Type I (90%): Bone, Skin, Tendon, dentin, fascia, cornea, later wound repair Type II: Cartilage, vitreous body, nucleus pulposus Type III: Reticulin -- skin, blood vessels, uterus, fetal tissue, granulation tissue Type IV: Basement membrane, basal lamina, lens

question

Type IV collagen Dx

answer

Alport syndrome (defective) and Goodpasture Syndrome (autoantibodies)

question

Type III collagen Dx

answer

Ehlers-Danlos, vascular type (uncommon)

question

Scurvy Osteogenesis Imperfecta Ehlers-Danlos Menkes

answer

Scurvy (RER): Hydroxylation of Proline and lysine Osteogenesis Imperfecta (RER): Formation of procollagen (triple helix) Ehlers-Danlos (outside fibroblast): Lysyl Oxidase, crosslinking of tropocollagen Menkes (outside fibroblast): ↓Cu absorption leads to defective lysyl oxidase/crosslinking

question

Joint dislocation, berry and aortic aneurysms, organ rupture

answer

Ehlers-Danlos syndromes (classical→Type V; vascular→Type III)

question

Brittle, kinky hair; growth retardation; hypotonia

answer

Menkes (↓Cu absorption and transport)

question

Marfan Syndrome

answer

Fibrillin defect

question

Emphysema

answer

↓ alpha-1 antitrypsin, leads to excess elastase activity

question

SNoW DRoP

answer

Southern blot = DNA Northern blot = RNA (mRNA levels, for gene expression) Western blot = Protein (used to confirm HIV) Southwestern = DNA binding proteins using oligonucleotide probes (TFs)

question

Indirect vs Direct ELISA

answer

Indirect = uses antigens to detect antibody in serum Direct = uses antibodies to detect antigens in serum

question

RNAi

answer

dsRNA complmentary to mRNA sequence of interest --> knocks down gene expression

question

Ex of genetic "Pleiotropy"

answer

PKU (light skin, intellectual disability, musty body odor)

question

Ex of "Loss of heterozygosity"

answer

Retinoblastoma (tumor suppressor genes)

question

Ex of "Dominant negative"

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Mutation of tumor suppressor in allosteric site (prevents wild type from binding)

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Ex of "Locus heterogeneity"

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Albinism

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Ex of "Allelic heterogeneity"

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Beta-Thalassemia

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"Heteroplasmy"

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mtDNA mutation (leads to variable expression)

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Hyperphagia, obesity, intellectual disability, hypogonadism, hypotonia

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Prader-Willi *25% maternal uniparental disomy

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"happy puppet", inappropriate laughter, seizures, ataxia, severe intellectual disability

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Angelman Syndrome *5% paternal uniparental disomy

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Ex of X-linked DOMINANT disease

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Hypophosphatemic rickets (vitamin D-resistant rickets, due to wasting of phosphate at proximal tubule)

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"Ragged red fibers" on muscle biopsy

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Mitochondrial disease - myopathy, lactic acidosis, CNS disorder.. all secondary to Ox Phos disorder

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Mutation in APC gene

answer

Familial Adenomatous Polyposis (AD, chromosome )

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Achilles tendon xanthoma

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Familial Hypercholesterolemia

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AVMs, GI bleeding, recurrent epistaxis, hematuria

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Hereditary Hemorrhagic Telangiectasia (Osler-Weber-Rendu syndrome) (AD, disorder of blood vessels)

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Hemolytic anemia, ↑ MCHC

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hereditary spherocytosis (AD, Ankyrin defect, Rx: splenectomy)

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Caudate atrophy (part of basal ganglia; voluntary movement, learning, memory) and ↓ GABA and ACh

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Huntington disease (AD, CAG repeats, chr. 4)

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Subluxation of lenses (up and temporal), floppy mitral valve, and arachnodectyly

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Marfan syndrome (AD, Fibrillin-1)

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Gene associated with MEN2a and MEN2b

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ret gene (AD)

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von Recklinghausen disease

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NF1 (AD, variable expression, but 100% penetrance)

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Juvenile cataracts, meningiomas, ependymomas, and bilateral acoustic schwannomas

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NF2 (AD)

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Numerous benign hamartomas

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Tuberous Sclerosis (AD, variable expression, incomplete penetrance)

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Numerous tumors (malignant and benign)

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von Hippel-Lindau disease (AD, deletion of VHL tumor suppressor, ch 3)

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X-linked recessive disorders (Be Wise, Fool's GOLD Heeds Silly HOpe)

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Bruton agammaglobulinemia Wiskott-Aldrich syndrome Fabry disease G6PD deficiency Ocular albinism Lesch-Nyhan syndrome Duchenne (and Becker) MD Hunter syndrome Hemophilia A and B Ornithine transcarbamylase deficiency

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Weakness in pelvic girdle, progressing superiorly

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Duchenne MD

question

Cause of death in DMD

answer

Dilated cardiomyopathy

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CTG tri-nucleotide repeat expansion in DMPK gene (myotonin protein kinase) Muscle wasting, arrhythmia, testicular atrophy, balding

answer

Myotonic Type 1

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2nd most common cause of genetic intellectual disability

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Fragile-X syndrome

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Signs of Fragile X

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"eXtra large testes, jaw, ears"

question

Genetics of Fragile X

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trinucleotide repeat (CGG), affects methylation and expression of FMR1 gene on X-chromosome

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Trinucleotide repeat expansion diseases: "X-Girlfriend's First Aid Helped Ace MY Test"

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Fragile-X (CGG) Friedreich ataxia (GAA) Huntington disease (CAG) Myotonic dystrophy (CTG)

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First and second trimester findings in Down syndrome (21)

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First: ↑ nuchal translucency hypoplastic nasal bone ↓ PAPP-A ↑ beta-hCG Second: ↓ alpha-fetoprotein ↓ estriol ↑ beta-hCG ↑ inhibin A

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First and second trimester findings in Edward syndrome (18)

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First: ↓ PAPP-A ↓ Beta-hCG Second: All ↓ (alpha-fetoprotein, beta-hCG, estriol, inhibin A)

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First trimester findings in Patau syndrome (13)

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↓ FREE beta-hCG ↓ PAPP-A ↑ nuchal translucency

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The "P's" of Patau syndrome (13)

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cleft liP or Palate holoProsencephaly Polydactyly

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Non-dysjunction in meiosis I vs meiosis II

answer

Meiosis I = 2 different maternal chromosomes Meiosis II = 2 of the (almost) same maternal chromosome

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Genetics of cri-du-chat syndrome

answer

microdeletion of short arm of chromosome 5 (5p-)

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Genetics of Williams syndrome

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microdeletion of long arm of chromosome 7 (includes elastin gene)

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Syndrome with hypercalcemia, well-developed verbal skills, and friendliness with strangers

answer

Williams syndrome

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Aberrant development of 3rd and 4th branchial pouches ("CATCH-22")

answer

Cleft palate Abnormal facies Thymic aplasia (T-cell deficiency) Cardiac defects Hypocalcemia (parathyroid dysplasia) *d/t microdeletion at chromosome 22q11

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Thymic, parathyroid, and cardiac defects

answer

DiGeorge syndrome

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Palate, Cardiac, and facial defects

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Velocardiofacial syndrome

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Fat-soluble vitamins

answer

A, D, E, K *require working gut and pancreas

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Dermatitis, glossitis, and diarrhea

answer

Vitamin B deficiencies

question

Name the B vitamins

answer

B1: thiamine (TPP) B2: riboflavin (FAD, FMN) B3: Niacin (NAD+) B5: pantothenic acid (CoA) B6: Pyridoxine (PLP) B7: Biotin B9: Folate B12: Colbalamin

question

Cofactor for several dehydrogenase reactions (Glycolysis --> TCA, HMP shunt, branched-chain ketoacid dehydrogenase)

answer

Bi: Thiamine

question

Deficiency of this vitamin leads to impaired glucose metabolism (ATP depletion is WORSENED by glucose infusion)

answer

B1: Thiamine - Wernicke-Korsakoff syndrome (medial dorsal nucleus of thalamus and mammillary bodies) - Dry and Wet Beriberi (symmetrical muscle wasting, hi-output cardiac failure)

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Cofactors for redox reactions

answer

B2: Riboflavin (FAD) B3: Niacin (NAD)

question

Deficiency of this vitamin leads to cheilosis and corneal vascularization (2 C's)

answer

B2: Riboflavin

question

Deficiency of this vitamin leads to Diarrhea, Dementia, and Dermatitis/hyperpigmentation (3 D's)

answer

B3: Niacin *symptoms of pellagra, can be caused by decreased tryptophan (Hartnup disease, malignant carcinoid syndrome, and isoniazid use)

question

Cofactor required for CoA and fatty acid sythase

answer

B5: pantothenate

question

Cofactor used for transamination, decarboxylation, and glycogen phosphorylase. Synthesis of 5-HT, NE, Epi, DA, GABA, histamine, heme, cystathionine, and niacin

answer

B6: Pyridoxine

question

Deficiency of this vitamin can lead to sideroblastic anemia d/t impaired hemoglobin synthesis + iron excess

answer

B6: Pyridoxine

question

Cofactor for homocysteine methyltransferase and methylmalonyl-CoA mutase

answer

B12: Colbalamin

question

Deficiency of this vitamin leads to megaloblastic anemia with hypersegmented PMNs, and degeneration of dorsal columns, lateral corticospinal tracts, and spinocerebellar tracts

answer

B12: Colbalamin

question

growth retardation, facial anomalies (microcephaly), photosensitive rash, immunodeficiency

answer

Blood Syndrome (DNA helicase mutation)

question

flushing, tachycardia, headache, nausea and vomiting, confusion

answer

cyanide poisoning (Rx: amyl nitrite, Na thiosulfate)

question

B vitamins req. for pyruvate dehydrogenase

answer

B1 (thymine pyrophosphate) --> Must be administered prior to glucose B2 (FADH2) B3 (NADH) B5 (CoA)

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Dx. with lethargy, liver problems, and Fanconi syndrome

answer

Hereditary Fructose Intolerance (Aldolase B)

question

Deficient Enzyme: Glucose-6-phosphatase (final step in glycogenolysis)

answer

von Gierke

question

Glycogen storage Dx: hypoglycemia, lactic acidosis, hyperuricemia, short stature, doll-like facies, emaciated extremities and protruding abdomen

answer

von Gierke

question

Deficient Enzyme: lysosomal alpha 1,4-glucosidase

answer

Pompe (acid maltase deficiency)

question

Glycogen storage Dx: cardiomegaly, weakness, death by 2 years; inclusion bodies composed of glycogen

answer

Pompe (acid maltase deficiency)

question

Conditions that increase indirect bilirubin

answer

Hemolysis Crigler-Najjar syndromes Gilbert syndrome newborn (low levels of conjugation enzymes- UDP glucuronyl transferase) Liver dmg

question

Conditions that increase direct bilirubin

answer

Liver dmg Bile duct obstruction Dubin-johnson (black liver) Rotor syndrome

question

Clay colored stools

answer

Bile-duct obstruction

question

Drugs of choice for UTI in pregnant woman

answer

Augmentin (amox + clavulanate) nitrofurantoin

question

Deficient Enzyme: Glycogen debranching enzyme

answer

Cori

question

Glycogen storage Dx: hypoglycemia with liver enlargement; glycogen has shortened outer branches with a glucose residue at the end

answer

Cori

question

Deficient Enzyme: Branching enzyme

answer

Andersen (amylopectinosis)

question

Glycogen storage Dx: infantile hypoglycemia, cirrhosis, death by 2 years; glycogen has very few branches

answer

Andersen (amylopectinosis)

question

Deficient Enzyme: Muscle glycogen phosphorylase

answer

McArdle

question

Glycogen storage Dx: muscle cramping and weakness with exercise, myoglobinuria

answer

McArdle

question

Deficient Enzyme: Hepatic glycogen phosphorylase

answer

Hers

question

Glycogen storage Dx: mild fasting hypoglycemia, hepatomegaly, cirrhosis; normal glycogen

answer

Hers

question

Symptoms resemble Marfan syndrome but with mental retardation and limited joint mobility ↑ levels of methionine

answer

Homocystinuria / cystathionino synthase deficiency

question

Lysosomal enzyme: Hexosaminidase Ganglioside GM2 accumulates

answer

Tay-Sachs

question

Lysosomal storage Dx: cherry red spots on macula, blindness, psychomotor retardation, death < 2 years, startle reflex

answer

Tay-Sachs

question

Lysosomal enzyme: Glucocerebrosidase Glucocerebroside accumulates

answer

Gaucher

question

Lysosomal storage Dx: Adult hepatosplenomegaly and fractures, pancytopenia, macrophages with "crumpled paper inclusions"

answer

Gaucher

question

Lysosomal enzyme: Sphingomyelinase Sphingomyelin accumulates

answer

Neimann-Pick

question

Lysosomal storage Dx: Severe M.R., hepatosplenomegaly, foamy macrophages, "zebra bodies" in inclusions, cherry red spot on macula (possible), early death

answer

Neimann-Pick

question

Missing enzyme: Phenylalanine hydroxylase Untreated: M.R., white-blond hair and fair skin

answer

Phenylketonuria

question

Missing enzyme: Homogentisate oxidase

answer

Alcaptonuria (build up of homogentisic acid, from phenylalanine metabolism)

question

Missing enzyme: Branched-chain keto-acid dehydrogenase

answer

Maple-Syrup Urine Disease (avoid leucine and

question

Triggers for hemolysis in G6PD

answer

Sulfonamides Dapsone infections Fava beans

question

Sx: short stature, increased incidence of AML, anaplastic aneima

answer

Fanconi anemia (loss of DNA cross-link repair)

question

Neonate: enlarged spleen and chronic hemolysis

answer

Pyruvate kinase deficiency (↓ATP, stiff RBC's)

question

Sx: shortness of breath during airplane ride or activity with ↓pO₂

answer

Hemoglobin Bs varient (heterozygous or homozygous)

question

Cell that relies on anaerobic glycolysis

answer

RBC's

question

Impaired OH- of proline residues

answer

Vit C deficiency (scurvy) --> weak b.v. walls d/t unstable triple helix

question

Bleeding in alcoholic patient

answer

clotting factor deficiency Vit K deficiency hyperspleenism (↓ platelets) Scurvy

question

Differences in Pompe vs Von Gierke Dx

answer

Pompe: cardiac and skeletal muscles, early death Von Gierke: Hypoglycemia and acidotic episodes

question

Drugs/toxins that cause tissue hypoxia --> lactic aid buildup

answer

Phenformin catecholamines isoniazid salicylate cyanide

question

OMP decarboxylase deficiency (part of UMP synthase)

answer

Orotic aciduria

question

Rate-limiting enzyme of glycolysis

answer

Phosphofructokinase-1

question

Role of carnitine palmitoyltransferase

answer

Transport long-chain fatty acids into the mitochondria

question

Cystathionine synthase deficiency: serum finding

answer

Elevated methionine and homocysteine

question

Infant with elevated serum ammonia

answer

Urea cycle defect -Orotic aciduria - ↓OTC - carbamoyl sythetase

question

Sx: Increased erythrocyte Zn-protophyrin

answer

Inhibited or defective ferrochelatase (lead poisoning, iron deficiency, genetic). Last step in heme synthesis does not occur

question

Sx: decrease in urinary coproporphyrins

answer

uroporphyrinogen decarboxylase deficiency and congenital erythropoietic porphyria (decreased uroporphyrinogen III synthase)

question

Sx: increased urinary and fecal coproporphyrins

answer

Hereditary coproporphyria (decreased activity of coproporphyrinogen oxidase)

question

Sx: infant with growth failure, vomiting and diarrhea, cataracts, liver dx, aminoaciduria, and mental retardation

answer

Classical galactosemia (deficiency of galatose-1-phosphate uridyltransferase)

question

Enzyme associated with negatively-birefringent, needle shaped crystals

answer

Gout - Xanathine Oxidase (often under-excretion of uric acid)

question

Enzyme associated with defect in purine (ATP and GTP) salvage pathway

answer

HGPRT - Lesch-Nyhan syndrome

question

Essential amino acids (PVT TIM HaLL)

answer

Phenylalanine, valine, tryptophan, threonine, isoleucine, methionine, histadine, lysine and leucine

question

Primary hemolytic anemias (association)

answer

Defects in glycolysis or the hexose monophosphate shunt (pentose phosphate pathway)

question

RBCs are unable to produce sufficient ATP to maintain the Na/K pump --> swelling and lysis

answer

Pyruvate Kinase deficiency

question

Citrate is a negative allosteric regulator of _________________, and a positive allosteric regulator of __________________.

answer

Negative: PFK-1 (glycolysis) Positive: cytosolic acetyl CoA carboxylase (fatty acid synthesis)

question

Neural Crest Cells

answer

- PNS - Schwann cells - Autonomic Ganglia - Chromaffin cells - Ondontoblasts - Megalocytes - Aorticopulmonary septum - pharyngeal arches

question

Negative Nikolsky sign, Antibodies against dystonin

answer

Bullous Pemphigoid

question

Mutation in E-cadherin (CDHI1)

answer

Associated with gastric adenocarcinomas and infiltrating lobular carcinomas

question

P450 Inducers (Bull Shit CRAP GPS induces my rage)

answer

Barbituates St. John's wort Carbamazepine Rifampin Alcohol (chronic) Phenytoin Griseofulvin Phenobarbital Sulfonylureas

question

P450 Inhibitors (VICK'S FACE All Over GQ stops ladies in their tracks)

answer

Valproate Isoniazid Cimetidine Ketoconazole Sulfonamides Fluconazole Alcohol (acute) Chloramphenicol Erythromycin (macrolides x-cept azithromycin) Amiodarone Omeprazole Grapefruit juice Quinidine

Biochemistry Steps Mnemonics – Biochemistry – Flashcards

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