Branched-chain amino acid metabolism

Branched-chain amino acid metabolism in muscle and liver... 

The acyl-Co A dehydrogenases are a family of mitochondrial flavoenzymes involved in fatty acid and branched chain amino-acid metabolism. In addition to long chain acyl-Co A dehydrogenases (LCADs), there are short/ branched chain acyl-CoA dehydrogenase (SBCAD) that act on 2-methyl branched chain acyl-CoA substrates of varying chain lengths. 

At this point, the pathways for branched-chain amino acid metabolism diverge. 

Bieber LL, Choi YR (1977) Isolation and identification of aliphatic short-chain acylcarnitines from beef heart possible role for carnitine in branched-chain amino acid metabolism. Proc Natl Acad Sci U S A 74 2795-2798... 

Figure 20.20 Pathways of branched-chain amino acid metabolism. A, B, C, D, E, and F indicate defects in valinemia, maple syrup urine disease, isovaleric acidemia, /3-hydroxyisovaleric aciduria, a-methyl-j3-hydroxybutyric aciduria, and methylmalonic aciduria, respectively.

Yeast-derived saturated short-medium chain and branched-chain aldehydes are formed from sugar metabolism, fatty acid metabolism and branched-chain amino acid metabolism (Fig 8D.7). In addition, hexanal, as well as hexenal isomers, are formed during the pre-fermentative stages of winemaking by the sequential action of grape lipoxygenase and hydroperoxide cleavage enzyme on linoleic and linolenic acid, respectively (Crouzet 1986). 

Harris, R.A., Joshi, M., Jeoung, N.H. Mechanisms responsible for regulation of branched-chain amino acid metabolism. Biochem. Biophys. Res. Com. 2004 313 391-396... 

Harper, A. E Miller, R. H and Block, K. F (1984). Branched-chain amino acid metabolism. 

Disorders of Branched Chain Amino Acid Metabolism... 

C. Leucine but none of the other amino acids listed is a branched-chain amino acid. The muscle has a very active branched-chain amino acid metabolic pathway and uses that pathway to provide energy for its own use. The products of leucine metabolism are acetyl-CoA and acetoacetate, which are used in the tricarboxylic acid cycle. Acetoacetate is activated by succinyl-CoA and cleaved to two molecules of acetyl-CoA in the P-ketothiolase reaction. The other branched-chain amino acids, valine, and isoleucine, yield succinyl-CoA and acetyl-CoA as products of their catabolism. 

An aspect of branched-chain amino-acid metabolism which may help in the control of fluxes is that the aminotransferases are very high in muscle, almost missing in liver, and have intermediate activity in the kidney, with the branched-chain a-keto acid dehydrogenase being very high in liver and kidney and less active in muscle. 

The control of branched-chain amino-acid metabolism lies with the branched-chain a-keto-acid dehydrogenase. This enzyme can be phosphorylated to produce an inactive form and, in turn, that enzyme can be dephosphorylated to produce the active form. 

It is not yet known whether the latter can be metabolized to obtain energy. In the nematodes H. polygyrus and Panagrellus redivivus branched-chain amino acid metabolism follows the same pathways as in mammalian liver (22). 

Muscle fuel utilization at rest is dependent on the serum levels of glucose, amino acids, and fatty acids. If blood glucose and amino acids are elevated, glucose will be converted to glycogen, and branched-chain amino acid metabolism will be high. Fatty acids will be used for acetyl CoA production and will satisfy the energy needs of the muscle under these conditions. 

Hutson SM, Fenstermacher D, Mahar C. Role of mitochondrial transamination in branched chain amino acid metabolism. J Biol Chem 1988 263 3618-3625. 

Mason, S.L. Ward, L.C. (1981). Branched chain amino acid metabolism in two avian species Cotumix columix Japonica and Callus domesHca. Comp. Biochem. Physiol, 69B, 265-72. 

Thiamine-dependent enzymes are involved in energy production, nucleic acid synthesis and branched-chain amino acid metabolism. 

The discovery of a novel pathway for biosynthesis of medium and short chain fatty acids in plants (a-keto acid elongation pathway, 1) raises the possibility (however unlikely) that medium-chain fatty acids (mcFAs) of certain oil seeds producing them may be derived by this pathway. Alternatively, these may be formed after release of elongating fatty acid chains from fatty acid synthase mediated biosynthesis (FAS) by specific medium chain thioesterases [2, 3,4]. Thus far the aKAE pathway is only known to occur in trichome glands of plants in the family Solanaceae. In the aKAE pathway, iso-, anteiso- or straight-chain keto acid products of branched-chain amino acid metabolism are elongated by one carbon (via acetate) per cycle. The final step is predicted to be oxidative decarboxylation to yield CoA activated acids. The mechanism that determines the chain length of aKAE products is not understood [1]. 

Roe CR, Roe DS. Detection of gene defects in branched-chain amino acid metabolism by tandem mass spectrometry of carnitine esters produced by cultured fibroblasts. Methods Enzymol. 2000 324 424-31. 

K Bartlett, AG Causey. Radiochemical high-performance liquid chromatography methods for the study of branched-chain amino acid metabolism. Methods Enzymol... 

Further reading Dancis, J. and Levitz, M. (1978). Abnormalities of branched-chain amino acid metabolism (hyper-valinaemia, maple syrup urine disease, isovaleric acidaemia and -methylcrotonic aciduria). In Stanbury, J.B., Wyngaarden, J.B. and Fredrickson, D.S. (eds.) The Metabolic Basis of Inherited Disease. 4th Ed., p. 397. (New York McGraw-Hill)... 

Hutson, S.M., Sweatt, A.J., and LaNoue, K.F., Branched-chain amino acid metabolism implications for establishing safe intakes, J. Nutr., 135, 1557S-1564S, 2005. 

Branched chain amino acid metabolism 251 Table 10.2. Serum and urine organic acids in two patients with isovaleric acidaemia (after Tanaka, 1975). 

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