Amino Acid Metabolism Flashcards
3 key cofactors for enzymes in AA metabolism
PLP: transaminase
Tetrahydrafolate (FH4-): 1 C transfers
Tetrahydrobiopterin (BH4): Ring hydroxylations (Phe–>Tyr)
True false, AA biosynthesis and degredation use only one enzyme
How many essential/non-essential AAs?
False
11 non- body can make
9 need to acquire in diet (10 for kids***)
Essential AAs
M.V. Pitthall
Methionine
Valine
Phenylalanine
Isoleucine
Tryptophan
Threonine
Histidine
Arginine *
Leucine
Lysine
What’s unique about tyrosine?
Tyrosine, a non-essential amino acid, requires dietary phenylalanine for synthesis. In the absence of phenylalanine hydroxylase, tyrosine becomes an essential amino acid.
Tyrosine gets an OH- group from Phe via phenylalinine hydroxylase.
What’s unique about cysteine?
Similarly, the biosynthesis of the nonessential amino acid cysteine requires dietary methionine to donate sulfur.
What role does BH4 play in conversion of Phe–>Tyr?
BH4 transfers e-’s from cofactor to H2O.
Glycolysis substrates –> what AA’s?
Pyruvate –> Ala via transamination.
3-PG –> Serine –> cysteine
Serine also <–> glycine
So, 4 AA’s can ultimately come from glycolytic intermediates.
What cofactor transfers Serine’s side chain to make the simplest AA, Gly?
How else can Ser be made?
Tetrahydrofolate (FH4-)
Serine can also be produced by b-elimination from dietary threonine
______ results from inherited mutations (autosomal recessive) in the amino acid carrier for cysteine and basic amino acids (lysine, arginine and ornithine).
Cystinuria.
…When transporters are defective, Cys can’t come back out of kidney lumen. It precipitates there, forming kidney stones
_____ and a _____ from homocysteine are joined to make cysteine.
Degradation of cysteine forms either _____ or _____.
Serine & sulfur from homocysteine –> Cys
Sulfuric acid: acidifies urine –WAY BODY CAN MODULATE PH OF URINE
PAPS: An “activated sulfate” for use in other reactions. – Can donate SO4’s in other rxns
Alanine is the major ______ amino acid. It is transaminated by ______ to pyruvate.
Ala = the gluconeogenic AA
alanini aminotransferase (ALT)
Where does ALT normally exist? If in the blood, it means what?
ALTs are liver enzymes that convert Ala to pyruvate and vice versa. ALT in blood means liver impairment
AA’s derived from TCA cycle:
OAA –> Aspartate –>Asparagine
alpha-KG –> glutamate, which can –> Pro & Arg…glutamate also–> glutamine
Again, AA’s derived from TCA:
From a-ketoglutarate:
glutamate
glutamine
arginine
proline
From oxaloacetate:
aspartate
aparagine
Glu –> alpha-KG via GDH
Another way to convert Glu –> alpha-KG:
Glu –> Gln
All amino acids synthesized from TCA cycle intermediates can be degraded to TCA cycle intermediates.
Essential amino acids can also degrade to TCA cycle intermediates and ketone bodies.
______degradation requires a tetrahydrofolate for conversion to glutamate. In folate deficiency, what accumulates.
Histidine requires FH4
In folate deficiency, an intermediate of histidine degradatin, FIGLU, accumulates
Which AA’s are ketogenic?
Thr, Lys, Iso and Trp
AA’s found elevated in Maple Syrup Disease:
Branch chain AA’s - Iso, Val, Leu: Maple syrup urine disease
WHat enzyme is defective in Maple Syrup Disease?
What characterizes this disease and what AA’s are involved?
Autosomal recessive deficiency in branched chain a-keto acid dehydrogenase
Classic: Presents in infants 1 week old with convulsions, vomitting, maple syrup odor in urine. Fatal if no tx
Labs: Elevated plasma and urine Val, Iso, Leu and keto-acids
Often hypoglycemic
Often ketoacidosis
Treatment:
Acute: hydration, transfusion
Long term: synthetic low BCAA diet
What about mild and intermittant forms of Maple Syrup Disease?
What tx and why?
Intermittant
sporadic bouts of MSUD
Mild
mental retardation
High dose thiamin increases TPP to help out moderately and mildly malfunctioning dehydrogenase enzyme at E1 subunit. Swamping it w/ cofactor gives enzyme best chance to work. Similar to PDH, alpha-keto acid dehydrogenase is inactivated when phosphorylated and active w/o PO4 bound.
