L.5 AA Metabolism Diseases and Coenzymes Flashcards
Histidinemia
-Histininase deficiency
-Histidine metabolism
-Elevated histidine
in blood/urine, very benign
Albinism
- Tyrosinase deficiency
- Tyrosine metabolism
- No melanin production, so are albino
Alkaptonuria
- Homogentistic oxidase deficiency
- Tyrosine metabolism
- Homogentisic acid accumulation in urine/tissues (causes oxidation)
- Causes crippling arthritis
Tyrosinemia Type I
- Fumaryl-Acetoacetate Hydrolase deficiency
- Tyrosine metabolism
- Accumulation of Fumarylacetoacetate/succinyl acetone in urine (cabbage like odor)
- Accumulation is toxic, causes liver/kidney failure
- Tx: Dietary restriction of phenylalanine/tyrosine, drug blocks production of Fumarylacetoacetate/succinyl acetone
Phenylketonuria
-Phenylalanine Hydroxylase deficiency (or BH4) deficiency
Phenylalanine/tyrosine metabolism
-Elevated phenylalanine phenylpyruvate/phenyllactate/phenylacetate in blood/urine (musty odor)
-Neurological problems (reduced production of catecholamines/high levels of phenylalanine prevent other AA entry to brain)
-Hypopigmentation from reduced melanin production (from lack of tyrosine)
Tx: Restrict phenylalanine, avoid aspartame (contains phenylalanine, supplement tyrosine
Tetrahydrobiopterin (BH4) Deficiency
-More severe form of PKU
-Affects more than phenylalanine metabolism
-BH4 needed for hydroxylation of: Phenylalanine (tyrosine production), Tyrosine (catecholamine synthesis), Tryptophan (serotonin/melatonin synthesis)
-Elevated phenylalanine phenylpyruvate/phenyllactate/phenylacetate in blood/urine (musty odor)
-Neurological problems
-Hypopigmentation
Tx: provide synthesized BH4
Methylmalonic Acidemia
- Methylmalonyl CoA Mutase deficiency/Vit B12 deficiency
- Valine/isoleucine/threonine/methionine metabolism
- Elevated levels of methylmalonyl acid in blood
- Causes metabolic acidosis/developmental problems
- Leads to secondary hyperammonemia bc accumulated metabolites inhibit activation of urea cycle via N-Acetylglutamate
Propionic Acidemia
- Propionyl CoA Carboxylase deficiency, biotin deficiency
- Valine/isoleucine/threonine/methionine metabolism
- Elevated 3-OH propionic acid
- Metabolic acidosis/developmental problems
- Leads to secondary hyperammonemia bc accumulated metabolites inhibit activation of urea cycle via N-Acetylglutamate
Homocystinuria
-Cystathionine Synthase deficiency/B6
-Methionine Metabolism
-High homocysteine in urine, high methionine and its metabolites in blood
-High homocysteine also from low BH4/B12
-Mental, retardation, osteoporosis, MI risk, lens dislocation
-Causes cysteine to become essential AA
Tx: restrict methionine, supplement cysteine
Cystathionuria
- Cystathionase deficiency/B6
- Methionine metabolism
- Accumulation of cystathionine
- No clinical symptom
Megaloblastic Anemia
-Folic Acid deficiency
-Folic acid makes Tetrahydrofolate (THF) -> THF makes:Purines,
Thymidine monophosphate (TMP), necessary for DNA synthesis, Methionine
-Histidine/glycine/serine metabolism
-Very Large RBCs (precursors grow, but can’t divide due to not enough TMP for DNA synthesis)
Maple Syrup Urine Disease
-Branched Chain a-Keto Acid Dehydrogenase deficiency
-Leucine/valine/isoleucine metabolism
-Accumulation of BCAAs in blood and their keto acids in blood/urine, (maple syrup urine)
-Neurological problems due to BCAAs and their keto acids = inefficient NT synthesis
Tx: BCAA restriction (not entirely limited bc are essential AAs)
Pellagra
- Tryptophan/B3 deficiency
- Tryptophan makes Serotonin/Melatonin and NAD/NADP
- Tryptophan metabolism
- Dermatitis, Diarrhea, Dementia, Death
B6/Pyridoxal-Phosphate
- Transamination and Deamination
- Methionine metabolism
- Cystathionine B-Synthase
- Cystathionase
Folic Acid/Tetrahydrofolate/THF
- One carbon transfer reactions
- Serine, Glycine, Methionine, Histidine metabolism
- Serine -> Glycine
- Methionine Synthase
- Purine and TMP synthesis
