MTC exam II week II Flashcards
What is the general design of amino acid degradation? What are the exceptions?
transfer the alpha amino group from the amino acid to alpha-ketogluterate. this forms glutamate and an alpha keto acid
exceptions: lys, thr, glutamate
ALT
alanine amino transferase
alanine + alpha-ketogluterate –> pyruvate + glutamate
AST
aspartate + alpha-ketogluterate –> oxaloacetate + glutamate
What is one co-factor required by amino transferases? What is their mechanism of action?
PLP, a B6 derivative. these are ping-pong enzymes
Where does oxidative deamination take place? What are the reactants and products? What is the enzyme?
mitochondria of liver and kidney. glutamate +NAD(P) –> alphaketogluterate + ammonia + NAD(P)H
enzyme is L-glutamate Dehydrogenase
L glutamate dehydrogenase
converts glutamate and NAD(P) into ammonia and alpha ketogluterate and NAD(P)H in the mitochondria of the liver and kidneys
what two amino acids are exclusively ketogenic?
Leu and Lys
What two amino acids are both ketogenic and glucogenic?
Phe, Iso, Tyr, Trp, Thr
what amino acids can be broken down to form pyruvate?
alanine, cystein, serine, and part of tryptophan
what amino acids are broken down to form alpha ketogluterate?
glutamin, glutamate proline
What amino acids form oxaloacetate?
aspartate and asparagine
what amino acids form acetoacetyl CoA
tryptophan (part of) and lysine
What amino acids require the transfer of a single Carbon?
Thr, His, Met, Gly
When is biotin used as a cofactor in amino acid degredation?
biotin is used as a cofactor when you need to make a new carboxyl group from CO2, as in the degradation of Val, Met, Iso, Thr
What enzyme generates THF from folate?
dihydrofolate reductase
dihydrofolate reductase
generates THF from folate
methionine adenosyl transferase
synthesizes SAM from ATP and methionine
What is cobalamin/B12 used for
regeneration of methionine from homocystein
what are the three pathways for glycine degradation?
- cleaved to CO2 and NH4 by glycine cleavage enzyme. NAD gets the H+ and uses THF as a cofactor
- glycine to serine using THF, pyridoxal phosphate. enzyme is serine hydroxymethyltransferase
- oxidation to glyoxylate to oxalate using NAD
What can be made from threonine?
2-amino-3-ketobutyrate yields glycine and acetyl CoA (ketogenic)
or
degraded to succinyl CoA (glucogenic)
What are the histidine products? Cofactors?
glutamate and alpha-ketogluterate
draw linkage between the cofactors and the sam cycle
see attached
homocysteinuria. other causes?
problems with the enzyme cystathionine synthase. build up of homocystein, which is excreted into the urine.
leads to thromboembolic events, lens dislocation, mental retardation, and osteoporosis. treated with a low met diet
other possible cause: difficulty with MTHFR (enzyme that turns homocystein into methionine)
what happens when ammonia is allowed to accumulate in the brain, biochemically
there is a depletion of glutamate and an increase in glutamine. without glutamate, the brain also doesn’t have enough of the neurotransmitter GABA
leads to osmotic swelling, coma, lethargy, and death
what is the alanine/glucose cycle?
between skeletal muscle and liver
proteins break down into amino acids and ammonia. ammonia added to alpha-ketoglurate to form glutamate. combine with pyruvate to form alanine and alphaketogluterate via alanine aminotransferase (ALT). alanine goes thru blood to liver, where it is digested to pyruvate and glutamate. glutamate forms urea, pyurvate becomes glucose, and glucose returns to blood.
glutaminase
releases ammonia from glutamine in the liver
draw urea cycle
see attached
what are three drugs used to treat urea cycle disorders?
sodium benzoate, phenylbutyrate and phenylacetate. act as a nitrogen sink and can be excreted by the kidneys
What is the one X-linked urea cycle disorder?
OTC deficiency
N-acetylglutamate synthetase
enzyme that convers glutamate and acetyl CoA to N-acetylglutamate. N acetylglutamate increases the activity of CPS-I.
Arginine increases the activity of Nacetylglutamate
What enzyme deficiency causes maple syrup urine disease?
ketoacid dehydrogenase that converts the keto acids of Val, Iso, and Leu into various CoA things
What cofactor is associated with ketoacid dehydrogenase
thiamine
What is the pathway for propinoyl CoA
comes from isobutryl CoA and 2 methylbutryl CoA (from Val and Iso. respectively)
goes to methylmalonyl CoA to succinate
propinoic acidemia
VOMIT: valine, odd chain fatty acids, methionine, isoleucine, and threonine
deficiency in propinoyl CoA carboxylase- cant get from propinoyl CoA to methylmalonyl CoA
failure to thrive, vomiting, resp. distress, anion gap metabolic acidosis, hypoglycemia, hyperammonimia. may be helped with biotin
propionyl CoA carboxylase
enzyme which converts propionyl CoA into methylmalonyl CoA. When deficient, causes propinoic acidemia
when does biotin convert holoenzymes into apoenzymes?
propinyl CoA carboxylase, pyruvate carbxylase, 2-methylcrotonyl CoA carboxylase, because these enzymes are biotinylated by holocarboxylase synthetase
biotinidase
the enzyme that elps recycle biotin. without it, you must supplement biotin or you see multiple carboxylase deficiency
