Enzymes involved in branched-chain amino acid metabolism in humans.
Branched-chain amino acids (leucine, isoleucine and valine) are structurally related to branched-chain fatty acids. Leucine is 2-amino-4-methyl-pentanoic acid, isoleucine is 2-amino-3-methyl-pentanoic acid, and valine is 2-amino-3-methyl-butanoic acid. Similar to fatty acid oxidation, leucine and isoleucine produce acetyl-coA. Additionally, leucine generates acetoacetate and isoleucine yields propionyl-coA. Valine oxidation produces propionyl-coA, which is converted into methylmalonyl-coA and succinyl-coA. Branched-chain aminotransferase catalyzes the first reaction in the catabolic pathway of branched-chain amino acids, a reversible transamination that converts branched-chain amino acids into branched-chain ketoacids. Simultaneously, glutamate is converted in 2-ketoglutarate. The branched-chain ketoacid dehydrogenase complex catalyzes the irreversible oxidative decarboxylation of branched-chain ketoacids to produce branched-chain acyl-coA intermediates, which then follow separate catabolic pathways. Human tissue distribution and function of most of the enzymes involved in branched-chain amino acid catabolism is unknown. Congenital deficiencies of the enzymes involved in branched-chain amino acid metabolism are generally rare disorders. Some of them are associated with reduced pyruvate dehydrogenase complex activity and respiratory chain dysfunction that may contribute to their clinical phenotype. The biochemical phenotype is characterized by accumulation of the substrate to the deficient enzyme and its carnitine and/or glycine derivatives. It was established at the beginning of the twentieth century that the plasma level of the branched-chain amino acids is increased in conditions associated with insulin resistance such as obesity and diabetes mellitus. However, the potential clinical relevance of this elevation is uncertain.
Nephrology Division, Hospital General Juan Cardona, c/Pardo Bazán s/n, 15406, Ferrol, Spain. madevaa@yahoo.com.
María M
0000-0002-9997-2568
MM
Adeva-Andany
Nephrology Division, Hospital General Juan Cardona, c/Pardo Bazán s/n, 15406, Ferrol, Spain.
Laura
L
López-Maside
Nephrology Division, Hospital General Juan Cardona, c/Pardo Bazán s/n, 15406, Ferrol, Spain.
Cristóbal
C
Donapetry-García
Nephrology Division, Hospital General Juan Cardona, c/Pardo Bazán s/n, 15406, Ferrol, Spain.
Carlos
C
Fernández-Fernández
Nephrology Division, Hospital General Juan Cardona, c/Pardo Bazán s/n, 15406, Ferrol, Spain.
Cristina
C
Sixto-Leal
D000597:Amino Acids, Branched-Chain / Q000378:metabolism*; D006801:Humans; D009097:Multienzyme Complexes / Q000378:metabolism*; D010084:Oxidation-Reduction
D000597:Amino Acids, Branched-Chain; D009097:Multienzyme Complexes
Acetyl-coA; Hydroxybutyrate; Isoleucine; Leucine; Valine