catabolism of amino acids Flashcards
(25 cards)
what stimulates the synthesis of N-acetylglutamate?
arginine
why will hyperammonemia cause CNS defects?
high NH4 leads to depletion of TCA cycle intermediates as well as decreased synthesis of NTs (all of the intermediates are busy trying to excrete the excess NH4)
what occurs with ornithine transcarbamoylase deficiency?
enzyme responsible for carbamoyl phosphate + ornithine –> citrulline is deficient, leads to high NH4/glutamine in the blood, “orotic acuduria” is the defining feature
how does orotic acuduria occur?
in OTC def, levels of carbamoyl phosphate increase and spill out of the mitochondria into the cytosol. CPS II (present in cytosol) converts it to orotic acid, which accumulates and can be found in the urine
what is an essential aa if OTC deficiency is present?
arginine. Since it is usually synthesized during the urea cycle, but cannot be synthesized if urea cycle cannot run
causes of elevated BUN? increased urinary NH4+ excretion?
inc BUN = impaired renal function/dehydration
inc NH4 = acidosis, starvation
glucogenic aa (3)
alanine, aspartate, glutamate
ketogenic aa (2)
leucine, lysine
both ketogenic and glycogenic aa
isoleucine, phenylalanine, tryptophan, tyrosine, threonine
tryptophan catabolism results in the production of-
Niacin
what is affected in maple syrup urine disease?
catabolism of branched chain aa because of defect in a-keto acid decarboxylase. ketoacidosis will occur because first step (transamination) occurs as usual
some pts with MSUD will respond to therapy with __ because?
thiamine
a-ketoacid dehydogenase complex has multiple subunits. E1 catalyzes a decarboxylation that uses thiamine as a cofactor.
PKU typically results from a defect in
phenylalanine hydroxylase
what becomes an essential aa when PKU present?
tyrosine
what cofactor is used by Phe hydroxylase
BH4 (tetrahydrobiopterin)
what used to be used to test for PKU? what has replaced it?
guthrie test, replaced with mass spec
what is the role of BH4?
donates H during hydroxylation reactions
why do some patients have PKU like disease but normal phenylalanine hydroxylase?
defect in BH4 metabolism- either unable to synthesize it (problem with dehydratase) or unable to recycle BH2 (problem with BH2 reductase)
which aa provide carbon skeletons for gluconeogenesis in the liver?
alanine and glutamine
what does the kidney use glutamine for?
glutamine –> glutamate + NH4, NH4 used to buffer urine
how does the kidney use glutamate?
glutamate –> a-ketoglutarate + NH4, a-ketoglutarate used for gluconeogenesis
major fuel of the kidney during:
normal
acidosis
fasting
normal- lactate
acidosis- glutamine
fasting- fatty acids
how does mm export NH4?
as glutamate or alanine
how does liver use alanine?
alanine –> pyruvate + NH4
pyruvate = gluconeogenesis
NH4 = urea cycle
