AMINO ACID METABOLISM - KAPLAN USMLE

- urea cycle defect
- condition: type I hyperammonemia
- metabolites accumulated: ammonia, glutamine, alanine

- urea cycle defect
- condition: type II hyperammonemia
- metabolites accumulated: ammonia, glutamine, orotate

- urea cycle defect
- condition: citrullinemia
- metabolites accumulated: citrulline

- urea cycle defect
- condition: argininosuccinic aciduria
- metabolites accumulated: argininosuccinate

- urea cycle defect
- condition: hyperargininemia
- metabolites accumulated: arginine

- AR defect in branched-chain ketoacid dehydrogenase
- high plasma & urine levels of branched-chain AA (leucine, valine, isoleucine) and their corresponding alpha-keto acids and alpha-hydroxyacids
- urine odor of maple syrup or burnt sugar
- brain damage + death by end of 1st yr if untreated

leu, lys

degraded tp acetyl-CoA or acetoacetyl-CoA --> both converted to ketone bodies

ile, phe, tyr, trp

all others

acetyl-CoA
acetoacetyl-CoA
oxaloacetate
fumarate
succinyl-CoA
alpha-keto glutarate
propionyl-CoA (converted to succinyl-CoA)

glycine, alanine, cysteine, serine, threonine, tryptophan

leucine, isoleucine

leucine, lysine
phenylalanine, tryptophan, tyrosine

asparagine, aspartate

tyrosine, phenylalanine

isoleucine, methionine, threonine, valine

proline, arginine, histidine, glutamine

2/2 deficiency of biotin, propionyl-CoA carboxylase, holocarboxylase synthase, or the enzyme that covalentloy attaches biotin to all carboxylases (in last case, additional organic acids accumulate)

2/2 deficiency in vitamin B12 or defect in methylmalonyl-CoA mutase

some pts respond well to megadose of vit B12

derivative of pyridoxine (vit B6)

acts as coenzyme for all transaminases

high protein diet --> glutamate accumulation --> increase in NAG --> CPS-1 activation

brain, liver, kidney

transferred to pyruvate to form alanine --> dumped into circulation --> picked up by liver, where it is converted back to pyruvate

gluconeogenesis

urea synthesis

deficiency in phenylalanine hydroxylase or dihydrobiopterin reductase

buildup of phenylalanine, phenylpyruvate, phenylacetate, phenyllactate in blood and urine

**tyrosine becomes an essential AA**

musty body odor
MR

PKU + impairment of catecholamine and serotonin synthesis

remove phenylalanine from diet (incl NutraSweet)

dipeptide containing phenylalanine + aspartic acid

phenylalanine

methionine

tyrosine becomes essential AA

cysteine becomes essential AA

coronary heart disease

independent of risk associated with elevated cholesterol

large amts. homocystine in urine

acquired or inherited

most often seen in children with FTT, lens displacement

deficiency in pyridoxine, folate, or vitamin B12

OR

inherited defect in either cystathionine synthase or methionine synthase

all above result in accumulation of homocysteine, which is readily oxidized to its disulfide form, homocystine

disulfide form of homocysteine

2/2 deficiency in pyridoxine or from genetic defect in cystathionase

large amts. cystathionine found in urine + blood

decreased dopamine in substantia nigra

1% of pop > 55yrs

tremors, postural instability, rigidity, bradykinesia

L-dopa + carbidopa

decreases extra-CNS effects of L-dopa

selectively inhibits aromatic acid decarboxylase outside CNS

does not cross BBB so does not inhibit conversion of L-dopa --> dopamine

neoplastic transformation of enterochromaffin cells

secrete excess serotonin

high levels of 5-HI in urine

act in part to spontaneously generate nitric oxide

any abnormality in pathway of heme synthesis

block early in pathway: intermediates buildup & are excreted in urine
block late in pathway: excreted in urine + feces, accumulate in skin

lead poisoning can be considered acquired porphyria b/c inhibits ALA DEHYDRATASE and HEME SYNTHASE (FERROCHELATASE)

massive hemolysis
block in heme catabolism
bile obstruction
liver damage

always jaundice

build stuff (need energy)

break stuff down (makes energy)