PathwayStep2443 PathwayStep2444 PathwayStep2445 PathwayStep2441 PathwayStep2442 PathwayStep2440 PathwayStep2435 PathwayStep2434 PathwayStep2433 PathwayStep2432 PathwayStep2439 PathwayStep2438 PathwayStep2437 PathwayStep2436 PathwayStep2430 PathwayStep2431 PathwayStep2426 PathwayStep2428 PathwayStep2427 PathwayStep2429 Branched-chain amino acid catabolism Authored: D'Eustachio, P, 2003-06-24 00:00:00 Edited: D'Eustachio, P, 0000-00-00 00:00:00 GENE ONTOLOGYGO:0009083 ISBN0079130356 Reactome Database ID Release 4370895 Reactome, http://www.reactome.org ReactomeREACT_197 The branched-chain amino acids, leucine, isoleucine, and valine, are all essential amino acids (i.e., ones required in the diet). They are major constituents of muscle protein. The breakdown of these amino acids starts with two common steps catalyzed by enzymes that act on all three amino acids: reversible transamination by branched-chain amino acid aminotransferase, and irreversible oxidative decarboxylation by the branched-chain ketoacid dehydrogenase complex. Isovaleryl-CoA is produced from leucine by these two reactions, alpha-methylbutyryl-CoA from isoleucine, and isobutyryl-CoA from valine. These acyl-CoA's undergo dehydrogenation, catalyzed by three different but related enzymes, and the breakdown pathways then diverge. Leucine is ultimately converted to acetyl-CoA and acetoacetate; isoleucine to acetyl-CoA and succinyl-CoA; and valine to succinyl-CoA. Under fasting conditions, substantial amounts of all three amino acids are generated by protein breakdown. In muscle, the final products of leucine, isoleucine, and valine catabolism can be fully oxidized via the citric acid cycle; in liver they can be directed toward the synthesis of ketone bodies (acetoacetate and acetyl-CoA) and glucose (succinyl-CoA) (Chuang & Shih 2001, Sweetman & Williams 2001). methylmalonate semialdehyde + NAD+ + CoA => propionyl-CoA + CO2 + NADH + H+ methylmalonyl semialdehyde + NADH + H+ <=> beta-hydroxyisobutyrate + NAD+ beta-hydroxyisobutyrate + NAD+ <=> methylmalonyl semialdehyde + NADH + H+ beta-hydroxyisobutyryl-CoA + H2O => beta-hydroxyisobutyrate + CoA a-ketoisocaproate, a-keto-b-methylvalerate, or a-ketoisovalerate + glutamate <=> leu, ile, or val + alpha-ketoglutarate [BCAT2] leu, ile, or val + alpha-ketoglutarate <=> a-ketoisocaproate, a-keto-b-methylvalerate, or a-ketoisovalerate + glutamate [BCAT2] a-ketoisocaproate, a-keto-b-methylvalerate, or a-ketoisovalerate + glutamate <=> leu, ile, or val + alpha-ketoglutarate [BCAT1] leu, ile, or val + alpha-ketoglutarate <=> a-ketoisocaproate, a-keto-b-methylvalerate, or a-ketoisovalerate + glutamate [BCAT1] Oxidative decarboxylation of branched-chain alpha-keto acids isovaleryl-CoA + FAD => beta-methylcrotonyl-CoA + FADH2 alpha-methylacetoacetyl-CoA + NADH + H+ <=> alpha-methyl-beta-hydroxybutyryl-CoA + NAD+ alpha-methyl-beta-hydroxybutyryl-CoA + NAD+ <=> alpha-methylacetoacetyl-CoA + NADH + H+ isobutyryl-CoA + FAD => methacrylyl-CoA + FADH2 alpha-methyl-acetoacetyl-CoA + CoA => propionyl-CoA + acetyl-CoA beta-methylglutaconyl-CoA + H2O <=> beta-hydroxy-beta-methylglutaryl-CoA beta-methylglutaconyl-CoA + ADP + orthophosphate + H2O <=> beta-methylcrotonyl-CoA + ATP + CO2 [MCCA] tiglyl-CoA + H2O <=> alpha-methyl-beta-hydroxybutyryl-CoA alpha-methylbutyryl-CoA + FAD => tiglyl-CoA + FADH2 beta-methylcrotonyl-CoA + ATP + CO2 <=> beta-methylglutaconyl-CoA + ADP + orthophosphate + H2O [MCCA] methacrylyl-CoA + H2O <=> beta-hydroxyisobutyryl-CoA