Catabolism of the Carbon Skeletons of Amino Acids

Excess amino acids are catabolized to amphibolic intermediates used as sources of energy or for carbohydrate and lipid biosynthesis. Initial reaction Transamination Remove any additional nitrogen Hydrocarbon skeleton

Amphibolic intermediates formed from the carbon skeletons of amino acids.

Transamination typically initiates amino acid catabolism Except Proline, hydroxyproline, threonine, and lysine.

Catabolism of L-asparagine and of L-glutamine to amphibolic intermediates.

Ornithine Ornithine-aminotransferase Elevate plasma and urinary ornithine Gyrate atrophy of the retina Hyperornithinemia- hyperammonemia syndrome Defective mitochondrial ornithine-citrulline antiporter

Catabolism of arginine

Catabolism of proline.

Type I hyperprolinemia Type II hyperprolinemia Proline dehydrogenase Type II hyperprolinemia Glutamate-semialdehyde dehydrogenase Δ1-pyrroline-3-hydroxy-5-carboxylate is excreted.

Catabolism of histidine.

Disorders of histidine catabolism Impaired histidase Histidinemia Urocanic aciduria Folic acid deficiency Figlu is excreted

Interconversion of serine and glycine

Reversible cleavage of glycine by the mitochondrial glycine synthase complex.

Primary hyperoxaluria Glycinuria Defect in renal tubular reabsorption Primary hyperoxaluria Failure to catabolize glyoxylate formed by deamination of glycine. Oxalate Urolithiasis, nephrocalcinosis Renal failure, hypertension

The cystine reductase reaction.

Catabolism of L-cysteine via the cysteine sulfinate pathway

Catabolism of L-cysteine via the 3-mercaptopyruvate pathway

abnormalities of cysteine metabolism Cystine-lysinuria (cystinuria) Defect in renal reabsorption Cystinosis Deposition of cystine crystals in tissues Homocystinuria Cardiovascular disease

Mixed disulfide of cysteine and homocysteine.

Conversion of threonine to glycine and acetyl-CoA.

Intermediates in L-hydroxyproline catabolism

Hyperhydroxyprolinemia Type II hyperprolinemia 4-hydroxyproline dehydrogenase Type II hyperprolinemia Second dehydrogenase

Intermediates in tyrosine catabolism.

Tyrosine metabolic disorders Type I tyrosinemia (tyrosinosis) fumarylacetoacetate hydrolase Type II tyrosinemia (Richner-Hanhart syndrome) Tyrosine aminotransferase Neonatal tyrosinemia Lowered p-hydroxyphenylpyruvate hydroxylase activity

Alkaptonuria Homogentisate oxidase The urine darkens on exposure to air arthritis and connective tissue pigmentation (ochronosis)

Phenylalanine metabolic disorders Hyperphenylalaninemias Type I, classic phenylketonuria or PKU) Defects in phenylalanine hydroxylase Types II and III defects in dihydrobiopterin reductase Types IV and V Defects in dihydrobiopterin biosynthesis DNA probes facilitate prenatal diagnosis Mental retardation

Alternative pathways of phenylalanine catabolism in phenylketonuria

Catabolism of L-lysine.

Periodic hyperlysinemia Lysine competitively inhibits liver arginase Hyperammonemia

Catabolism of L-tryptophan

Formation of xanthurenate in vitamin B6 deficiency

Hartnup disease Impaired intestinal and renal transport of tryptophan and other neutral amino acids

Formation of S-adenosylmethionine

Conversion of methionine to propionyl- CoA

branched-chain –keto acid dehydrogenase The initial reactions are common to all three branched-chain amino acids branched-chain –keto acid dehydrogenase Multimeric enzyme complex A decarboxylase, a transacylase a dihydrolipoyl dehydrogenase Being inactivated by phosphorylation

The analogous first three reactions in the catabolism of leucine, valine, and isoleucine.

METABOLIC DISORDERS OF BRANCHEDCHAIN AMINO ACID CATABOLISM Maple syrup urine disease (branched-chain ketonuria) α-keto acid decarboxylase complex Plasma and urinary levels of leucine, isoleucine, valine, α-keto acids, and α-hydroxy acids (reduced α-keto acids) are elevated Isovaleric acidemia Isovaleryl-CoA dehydrogenase

Catabolism of the β-methylcrotonyl- CoA formed from L-leucine

Subsequent catabolism of the tiglyl- CoA formed from L-isoleucine.

Subsequent catabolism of the methacrylyl-CoA formed from L-valine

Summary Excess amino acids are catabolized to amphibolic intermediates used as sources of energy or for carbohydrate and lipid biosynthesis. Initial reaction Transamination Remove any additional nitrogen Hydrocarbon skeleton To amphibolic intermediates

Metabolic diseases associated with glycine catabolism Glycinuria Primary hyperoxaluria Metabolic disorders of cysteine catabolism Cystine-lysinuria, Cystine storage disease, Homocystinurias

Metabolic diseases of tyrosine catabolism Tyrosinosis, Richner-Hanhart syndrome, Neonatal tyrosinemia, Alkaptonuria Metabolic disorders of phenylalanine catabolism Phenylketonuria (PKU) Several hyperphenylalaninemias.

Metabolic diseases of lysine catabolism Hyperlysinemiaammonemia Forms Periodic Persistent

Metabolic disorders of branched-chain amino acid catabolism Hypervalinemia Maple syrup urine disease Intermittent branched-chain ketonuria Isovaleric acidemia Methylmalonic aciduria