Amino Acid Metabolism Flashcards
Name the following:
Purely ketogenic amino acids (2)
Glucogenic and ketogenic amino acids (5)
Glucogenic amino acids (13)
Lys, Leu
Phe, Tyr, Trp, Ile, Thr
Everything else
Non-Ketotic Hyperglycinemia: Cause Diagnosis Presentation (Infants and Survivors) Treatment
Inherited deficiency of Gly cleavage enzyme
Elevated Gly in blood and CSF
Infants - seizures, coma, apnea, high mortality
Survivors - severe neurological deficits
Benzoic acid and NMDA receptor blockers
Homocystineuria:
Cause
Abnormalities
Treatment
Deficiency of cystathionine synthase.
INCREASED HOMOCYSTEINE
Osetoporosis, ectopia lentis, thromboemblism, mental deficiency, psychiatric problems
High doses of B6, B9, or B12, Methionine restriction, betaine to stimulate homocysteine to Met reaction
Maple Syrup Urine Disease: Cause Abnormalities Diagnosis Clinical course Treatment
Deficiency of branched-chain alpha-ketoacid dehydrogenase
Accumulation of Val, Leu, Ile and their alpha-ketoacids
Amino or organic acid profiling (newborn screening)
Complete enzyme deficiency causes neonatal encephalopathy and early death (protein intolerance in survivors with incomplete deficiency)
Few respond to thiamine (B1), rigorous diet with no Val, Ile, Leu
Methylmalonic Acidemia: Cause Presentation Mechanism Treatment
Inherited deficiency of methylmalonyl-CoA mutase
Episodes of metabolic acidosis
Methylmalonic acid builds up causing acidosis (ketosis in acute crisis)
Treatment = Adenosyl-cobalamin, restriction of dietary protein, avoidance of stress and fasting, antibiotics during acute crisis
Propionic Acidemia:
Cause
Presentation
Treatment
Inherited deficiency of propionyl-CoA carboxylase
Recurrent episodes of metabolic acidosis and neurologic complications
Biotin rarely effective, treat like methylmalonic acidemia
Phenylketonuria (PKU): Cause Mechanism Pathogenesis Diagnosis Mothers with PKU
Deficiency of Phe hydroxylase (Phe –> Tyr)
Transamination reaction becomes main reaction and Phe, phenylpyruvate, phenyllactate and phenylacetate accumulate
Brain damage, mental retardation, light skin and hair, mousy odor of infant
Newborn screening
Excess Phe crosses placenta causing fetal brain damage
Alkaptonuria:
Cause
Presentation
Dificiency of homogentisate oxidase
Black pigment deposits in cartilage, arthritis, black urine
Tyrosinemia:
Cause
Presentation
Treatment
Deficiency of fumarylacetoacetate hydrolase
Liver and kidney failure
Phe and Tyr restriction and p-hydroxyphenylpyruvate oxidase inhibitor (NTBC)
Histidinemia:
Deficiencies (2)
Accumulating substance in each deficiency
1) Folate - N-formiminoglutamate (FIGLU) accumulation
2) Histidase - HISTIDINE accumulation, forming
imidazolepyruvate (no clinical phenotype)
Oculocutaneous Albinism:
Cause
Presentation
Tyr deficiency or Tyr transporter deficiency in melanosome membrane
Light hair and skin (benign)
synthesis of Non-Essential AA
alanine + alpha-ketoglutarate –> [ALT= alanine transaminase//B6] –> Pyruvate + glutamate
(ALanine//ALt//Pyr)
aspartate + alpha-ketoglutarate –> [AST=aspartate transaminase//B6] –> Oxaloacetate
(ASpartate//ASt//Ox)
What is used to mop up extra ammonia to prevent toxicity?
Glutamine
metabolism of small aa
they get converted to Glycine
1) trimethylamine (rotten fish smell)
2) CO2, NH3 (via THF)
3) Oxalate
cc: non-ketotic hyperclycemia
- deficiency in glycine cleavage enzyme
- elevated glycine in blood and CSF
- presentation = seizures/coma
- treatment: benzoic acid and MNDA receptor blockers
Methionine cycle
Methionine –> SAM –> SAH –> homocysteine –> [serine + [cystathionine synthase//b6] –> cystathione –> cysteine –> glucogenic products
Homocysteine –> (b12) –> methionine
