Branched-chain 2-oxoacid dehydrogenase

BCOADC branched-chain 2-oxoacid dehydrogenase complex... 

Lau, K.S. Fatania, H.R. Randle, P.J. Regulation of the branched chain 2-oxoacid dehydrogenase kinase reaction. FEBS Lett., 144, 57-62 (1982)... 

Lawson, R. Cook, K.G. Yeaman, S.J. Rapid purification of bovine kidney branched-chain 2-oxoacid dehydrogenase complex containing endogenous kinase activity. FEBS Lett., 157, 54-58 (1982)... 

Amino acid catabohsm is particularly important dining starvation. Because of the mass of muscle, amino acid catabohsm is particularly important in this tissue which, in starvation, supplies the liver with most of its gluconeogenic precursors (see also Fig. 13-11). Amino acids resulting from proteolysis during starvation are interconverted in the muscle so that 60% of the amino acid mass that leaves the muscle is either glutamine or alanine. The branched-chain amino acids valine, leucine, and isoleucine, which are aU essential amino acids, are deaminated in muscle by a specific aminotransferase, and the corresponding 2-oxoacids are transported to the liver for further metabohsm via branched-chain 2-oxoacid dehydrogenase (BCOADH). The aminotransferase is inactive in the hver, and this ensures that the peripheral tissues are supphed with valine, leucine, and isoleucine. 

Within many tissues the enzymatic activities of the pyruvate and branched chain oxoacid dehydrogenases complexes are controlled in part by a phosphorylation -dephosphorylation mechanism (see Eq. 17-9). Phosphorylation of the decarboxylase subunit by an ATP-dependent kinase produces an inactive phosphoenzyme. A phosphatase reactivates the dehydrogenase to complete the regulatory cycle (see Eq. 17-9 and associated discussion). The regulation is apparently accomplished, in part, by controlling the affinity of the protein for... 

In a rare autosomal recessive condition (discovered in 1954) the urine and perspiration has a maple syrup odor/ High concentrations of the branched-chain 2-oxoacids formed by transamination of valine, leucine, and isoleucine are present, and the odor arises from decomposition products of these acids. The branched-chain amino acids as well as the related alcohols also accumulate in the blood and are found in the urine. The biochemical defect lies in the enzyme catalyzing oxidative decarboxylation of the oxoacids, as is indicated in Fig. 24-18. Insertions, deletions, and substitutions may be present in any of the subunits (Figs. 15-14,15-15). The disease which may affect one person in 200,000, is usually fatal in early childhood if untreated. Children suffer seizures, mental retardation, and coma. They may survive on a low-protein (gelatin) diet supplemented with essential amino acids, but treatment is difficult and a sudden relapse is apt to prove fatal. Some patients respond to administration of thiamin at 20 times the normal daily requirement. The branched-chain oxoacid dehydrogenase from some of these children shows a reduced affinity for the essential coenzyme thiamin diphosphate.d... 

Branched-chain-oxoacid dehydrogenase complex, which is responsible for the oxidative decarboxylation of the oxoacids derived from leucine, isoleucine and valine. Increased concentrations of all 3 branched chain amino acids and their oxoacids in urine, plasma and cerebrospinal fluid. Serum tilso contains alloiso-leucine (probably derived from isoleucine). Urine has characteristic odor. Marked cerebral degeneration apparently shortly after birth. Usually fatal within weeks or months of birth. 

Figure 8.17 The metabolism of branched-chain amino acids in muscle and the fate of the nitrogen and oxoacids. The a-NH2 group is transferred to form glutamate which is then aminated to form glutamine. The ammonia required for aminab on arises from glutamate via glutamate dehydrogenase, but originally from the transamination of the branded chain amino acids. Hence, they provide both nitrogen atoms for glutamine formation.

The intermediary metabolism has multienzyme complexes which, in a complex reaction, catalyze the oxidative decarboxylation of 2-oxoacids and the transfer to coenzyme A of the acyl residue produced. NAD" acts as the electron acceptor. In addition, thiamine diphosphate, lipoamide, and FAD are also involved in the reaction. The oxoacid dehydrogenases include a) the pyruvate dehydrogenase complex (PDH, pyruvate acetyl CoA), b) the 2-oxoglutarate dehydrogenase complex of the tricarboxylic acid cycle (ODH, 2-oxoglutarate succinyl CoA), and c) the branched chain dehydrogenase complex, which is involved in the catabolism of valine, leucine, and isoleucine (see p. 414). 

NAD+ serves as the oxidant. The reaction is catalyzed by a complex of enzymes whose molecular mass varies from 4 to 10 x 106, depending on the species and exact substrate.297 Separate oxoacid dehydrogenase systems are known for pyruvate,298-300 2-oxoglut-arate,301 and the 2-oxoacids with branched side chains derived metabolically from leucine, isoleucine, and... 

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