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66 Cards in this Set
- Front
- Back
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What parts of metabolism occur in the mitochondria? (4)
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beta-oxidation of fatty acids
acetyl-CoA production TCA cycle oxidative phosphorylation |
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What parts of metabolism occur in the cytosol? (5)
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glycolysis
fatty acid synthesis HMP shunt protein synthesis (RER) steroid synthesis (SER) |
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What parts of metabolism occur in the cytosol AND the mitochondira?
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Heme synthesis
Urea cycle Gluconeogenesis HUG takes 2! |
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What do kinases do?
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use ATP to add high-energy phosphate groups to substrates
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What do phosphorylases do?
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add inorganic phosphate groups sans ATP
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What do dehydrogenases do?
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oxidize substrates
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What do carboxylases do?
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transfer CO2 groups using biotin
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When is NAD used as an electron receptor?
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Catabolic processes to carry reducing equivalents away
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When is NADP used as an electron acceptor?
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Anabolic processes (steroid and FA synth)
respiratory burst cytochrome P-450 glutathione reductase |
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What are the locations and purpose of glucokinase?
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In liver and beta cells instead of hexokinase
phosphorylates excess glucose after a large meal so it can be sequestered in the liver |
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What does arsenic do?
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Inhibits lipoic acid in conversion of pyruvate to acetyl-CoA
--> vomiting, rice water stools, garlic breath |
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What occurs in pyruvate dehydrogenase deficiency?
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backup of pyruvate and alanine --> lactic acidosis
--> neurologic defects congenital or acquired (B1 deficiency) |
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How is pyruvate dehydrogenase deficiency treated?
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Intake of ketogenic nutrients:
fat lysine leucine |
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Name 4 direct inhibitors of the electron transport chain:
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Rotenone
cyanide (CN) antimycin A carbon monoxide (CO) |
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How does oligomycin work as a poison?
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Directly inhibits mitochondrial ATP synthase, stopping the ETC
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Name 3 uncoupling agents
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2,4-DNP
aspiring (acetylsalicylic acid) - responsible for fevers after overdose thermogenin (in brown fat) |
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How do uncoupling agents work?
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increased permeability of mitochondrial membrane causes loss of the proton gradient and increased O2 consumption; ATP synthesis stops but the ETC continues --> heat
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What is the respiratory burst?
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activation of membrane-bound NADPH oxidase creates ROIs for immune response in neutrophils, monocytes
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How is the respiratory burst affected in chronic granulomatous disease?
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patients neutralize their own hydrogen peroxide (due to a NADPH oxidase defect) and can only make ROIs from peroxide produced by invading organisms
they become predisposed to catalase-positive invaders like S. aureus and Apsergillus |
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What happens in glucose-6-phosphate dehydrogenase deficiency?
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impairs the HMP shunt, --> low NADPH
--> hemolytic anemia in response to oxidizing agents and free radicals from infections |
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What are Heinz bodies?
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oxidized hemoglobin precipitated in RBCs due to glucose-6-phosphatase dehydrogenase deficiency
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What is the inheritance and epidemiology of glucose-6-phosphate dehydrogenase deficiency?
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X-linked recessive
--> increased malarial resistance most common IEM; more common in blacks |
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What are bite cells?
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RBCs with chunks taken out of them - from phagocytic removal of Heinz bodies by splenic macrophages
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What is essential fructosuria?
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defect in fructokinase
AR inhertance benign - fructose doesn't enter cells |
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What is fructose intolerance?
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hereditary lack of aldolase B
AR inhertance fructose-1-P accumulates and decreased phosphate inhibits glycogenolysis and gluconeogenesis --> hypoglycemia jaundice cirrhosis vomiting |
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What occurs in galactokinase deficiency?
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galactilol accumulates from dietary galactose
--> galactosemia/uria, infantile cataracts |
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What is classic galactosemia?
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absence of galactose-1-phosphate uridyltransferase
--> accumulation of toxic subtances galactitol accumulates in lens failure to thrive jaundice hepatomegaly infantile cataracts mental retardation |
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How does hyperglycemia cause cataracts, retinopathy, neuropathy, and nephropathy?
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cells trap glucose inside by converting it to sorbitol via aldose reductase
cells lacking sorbitol dehydrogenase to convert sorbitol to fructose can accumulate sorbitol --> osmotic damage |
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What are features of ammonia intoxication?
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tremor
slurred speech somnolence vomiting cerebral edema blurred vision |
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What is the pathogenesis of hyperammonemia?
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acquired (liver disease) or hereditary (urea cycle enzyme deficiency)
excess NH4 depletes alpha-ketoglutarate --> TCA inhibition |
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What is the treatment for hyperammonemia?
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limit dietary protein
benzoate or phenylbutyrate (bind AAs --> excretion) lactulose to acidify GI and trap NH4 for excretion |
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What occurs in ornithine transcarbamoylase (OTC) deficiency?
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x-linked recessive enzyme defect --> excess carbamoyl phosphate --> conversion to orotic acid
--> orotic acidemia/uria, low BUN, hyperammonemia |
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What causes phenylketonuria?
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Low phenylalanine hydroxylase or tetrahydrobiopterin cofactor
tyrosine becomes an essential AA; accumulating phenylalanine --> phenylketones in urine |
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What are features of phenylketonuria?
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normal at birth (maternal enzyme functional)
mental and growth retardation seizures fair skin eczema musty BO |
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Name 3 phenylketones
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phenylacetate
phenyllactate phenylpyruvate |
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What occurs with untreated maternal PKU?
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fetus has microcephaly, retardation, and CHD
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What occurs in alkaptonuria/ochornosis?
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homogentisic acid oxidase deficiency in tyroside degradation
benign disease --> dark CT, browth sclera, black standing urine; arthralgias possible (toxic cartilage degredation) |
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What are three causes of albinism?
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1. loss of tyrosinase --> impaired melanin synthesis
2. tyrosine transporter deficiency --> low tyrosine availability 3. failed migration of neural crest cells |
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How is albinism inherited?
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variable - locus heterogeneity
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What are the 3 causes of homocysteinuria?
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1. cystathione synthase deficiency
2. decreased cystathione synthase affinity for PLP/B6 3. homocysteine methyltransferase deficiency |
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How is cystathione synthase deficiency treated?
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reduce dietary methionine
supplement dietary cysteine and B12 |
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How is reduced cystathione synthase affinity for PLP treated?
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B6 supplementation
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What are features of homocystinuria?
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high homocysteine in urine
mental retardation osteoporosis tall stature kyphosis lens subluxation (down and in) atherosclerosis and infarcts |
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What happens in cystinuria?
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defect of renal PCT AA transporter for cysteine, ornitine, lysine, and arginine
--> cystine kidney stones |
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How is cystinuria treated?
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acetazolamide to alkanize urine
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What is the mechanism of acetazolamide?
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carbonic anhydrase inhibitor
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What is cystine compared to cysteine?
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Cystine = 2 cysteines connected by disulfide bond
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What causes maple syrup urine disease?
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deficient alpha-ketoacid dehydrogenase --> blocked degradation of branched AAs
I Love Vermont = Ile, Leu, Val --> alpha ketoacidemia |
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What are features of maple syrup urine disease?
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severe CNS deficit
mental retardation death urine that smells like syrup |
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What causes Hartnup disease?
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defective neutral AA transporter renal/intestinal epithelium
--> tryptophan excretion in urine and decreased gut absorption --> pellagra |
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Name 4 glycogen storage diseases
Very Poor Carb Metabolism |
Von Gierke's (I)
Pompe's (II) Cori's (III) McArdles (IV) |
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What happens in Von Gierke's disease?
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deficient glucose-6-phosphatase
--> severe fasting hypoglycemia increased liver glycgen increased blood lactate hepatomegaly |
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What happens in Pompe's disease?
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lysosomal alpha-1,4-glucosidase (acid maltase) deficiency
--> cardiomegaly, systemic findings (liver, muscle) early death |
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What happens in Cori's disease?
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debranching enzyme (alpha-1,6-glucosidase) deficiency
--> normal blood lactate gluconeogenesis intact milder hypoglycemia and liver buildup |
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What happens in McArdle's disease?
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skeletal muscle glycogen phosphorylase deficiency
McArdle's = muscle muscle cramps and myoglobinuria with exercise due to built-up unusable glycogen |
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What happens in Fabry's LSD?
enzyme substrate findings |
alpha-galactosidase A
ceramide trihexoside --> hand/feet neuropathy angiokeratomas CVD renal disease |
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Which 2 lysosomal storage diseases has X-linked recessive inheritance?
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Fabry's
Hunter's |
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Which lysosomal storage disease is most common?
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Gaucher's
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What happens in Gaucher's LSD?
enzyme substrate findings |
glucocerebrosidase
glucocerebroside -->hepatosplenomegaly aseptic femoral necrosis bone crises Gaucher's cells - crumpled-tissue macs |
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What happens in Niemann-Pick LSD?
enzyme substrate findings |
sphingomyelinase
sphingomyelin --> progressive neurodegeneration hepatosplenomegaly cherry-red macular spot foam cells |
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What happens in Tay-Sachs LSD?
enzyme substrate findings |
hexosaminidase A
GM2 ganglioside --> progressive neurodegeneration developmental delay cherry-red macular spot onion-skin lysosomes NO hepatosplenomegaly |
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What happens in Krabbe's LSD?
enzyme substrate findings |
beta-galactocerebrosidase
galactocerebroside --> peripheral neuropathy developmental delay optic atrophy globoid cells |
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What happens in metachromatic leukodystrophy LSD?
enzyme substrate findings |
arysulfatase A
cerebroside sulfate --> central/peripheral demyelination w/ ataxia and dementia |
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Name 2 mucopolysaccharidoses
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Hurler's syndrome
Hunter's syndrome |
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What happens in Hurler's syndrome LSD?
enzyme substrate findings |
alpha-L-udironidase
Heparan sulfate, dermatan sulfate --> developmental delay, gargoylism airway obstruction corneal clouding hepatosplenomegaly |
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What happens in Hunter's syndrome LSD?`
enzyme substrate findings |
iduronate sulfatase
heparan sulfate, dermatan sulfate Hurler's minus aggression and corneal clouding |
