Transamination Typically Initiates amino acid Catabolism
المؤلف:
Peter J. Kennelly, Kathleen M. Botham, Owen P. McGuinness, Victor W. Rodwell, P. Anthony Weil
المصدر:
Harpers Illustrated Biochemistry
الجزء والصفحة:
32nd edition.p291-293
2025-08-18
415
Removal of α-amino nitrogen by transamination, catalyzed by a transaminase (Figure 1), is the first catabolic reaction of most of the protein amino acids. The exceptions are proline, hydroxyproline, threonine, and lysine, whose α-amino groups do not participate in transamination. The hydrocarbon skeletons that remain are then degraded to amphibolic intermediates as outlined in Figure 2.
Fig1. Transamination. The reaction is freely reversible with an equilibrium constant close to unity.
Fig2. Overview of the amphibolic intermediates that result from catabolism of the protein amino acids.
Asparagine & Aspartate Form Oxaloacetate
All four carbons of asparagine and of aspartate form oxaloacetate via subsequent reactions catalyzed by asparaginase (EC 3.5.1.1) and a transaminase.
Asparagine + H2O → Aspartate + NH4+
Aspartate + Pyruvate → Alanine + Oxaloacetate
Glutamine & Glutamate Form α-Ketoglutarate
Successive reactions catalyzed by glutaminase (EC 3.5.1.2) and a transaminase form α-ketoglutarate.
Glutamine + H2O → Glutamate + NH4+
Glutamate + Pyruvate → Alanine + α-Ketoglutarate
While both glutamate and aspartate are substrates for the same transaminase, metabolic defects in transaminases, which fulfill central amphibolic functions, may be incompatible with life. Consequently, no known metabolic defect is associated with these two short catabolic pathways that convert asparagine and glutamine to amphibolic intermediates.
Proline
The catabolism of proline takes place in mitochondria. Since proline does not participate in transamination, its α-amino nitrogen is retained throughout a two-stage oxidation to glutamate. Oxidation to Δ1-pyrroline-5-carboxylate is catalyzed by proline dehydrogenase, EC 1.5.5.2. Subsequent oxidation to glutamate is catalyzed by Δ1-pyrroline-5-carboxylate dehydrogenase (also called glutamate-γ-semialdehyde dehydrogenase, EC 1.2.1.88; Figure 3). There are two metabolic disorders of proline catabolism. Inherited as autosomal recessive traits, both are consistent with a normal adult life. The metabolic block in type I hyperprolinemia is at proline dehydrogenase. There is no associated impairment of hydroxy proline catabolism. The metabolic block in type II hyperprolinemiais at Δ1-pyrroline-5-carboxylate dehydrogenase, which also participates in the catabolism of arginine, ornithine, and hydroxyproline. Since proline and hydroxyproline catabolism are affected, both Δ1-pyrroline-5-carboxylate and Δ1-pyrroline-3-hydroxy-5-carboxylate are excreted.
Fig3. Catabolism of proline. Red bars and circled numerals indicate the locus of the inherited metabolic defects in 1 type-I hyperprolinemia and 2 type-II hyperprolinemia. In this and subsequent figures, blue highlights emphasize the portions of the molecules that are undergoing chemical change.
Arginine & Ornithine
The initial reactions in arginine catabolism are conversion to ornithine followed by transamination of ornithine to glutamate-γ semialdehyde (Figure 4). Subsequent catabolism of glutamate γ-semialdehyde toα-ketoglutarateoccurs as described for proline (see Figure 3). Mutations in ornithine δ-aminotransferase (ornithine transaminase, EC 2.6.1.13) elevate plasma and urinary ornithine, and are associated with gyrate atrophy of the choroid and retina. Treatment involves restricting dietary arginine. In the hyperornithinemia–hyperammonemia syn drome, a defective ORC1 mitochondrial ornithine-citrulline antiporter impairs transport of ornithine into mitochondria, where it participates in urea synthesis.
Fig 4. Catabolism of arginine. Arginase-catalyzed cleavage of l-arginine forms urea and l-ornithine. This reaction (red bar) represents the site of the inherited metabolic defect in hyperargininemia. Subsequent transamination of ornithine to glutamate-γ-semialdehyde is followed by its oxidation to α-ketoglutarate.
Histidine
Catabolism of histidine proceeds via urocanate, 4-imidazolone 5-propionate, and N-formiminoglutamate (Figlu). Formimino group transfer to tetrahydrofolate forms glutamate, then α-ketoglutarate (Figure 5). In folic acid deficiency, transfer of the formimino group is impaired, and Figlu is excreted. Excretion of Figlu following a dose of histidine thus can be used to detect folic acid deficiency. Benign disorders of histidine catabolism include histidinemia and urocanic aciduria associated with impaired histidase and urocanase, respectively.
Fig5. Catabolism ofl-histidine to α-ketoglutarate. (H4 folate, tetrahydrofolate.) The red bar indicates the site of an inherited metabolic defect.
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