Effect of alpha-ketoacid dehydrogenase phosphorylation on branched-chain amino acid metabolism in muscle.
The regulation of leucine and valine metabolism was evaluated in skeletal muscle of perfused rat hindlimb. Control of the branched-chain alpha-ketoacid dehydrogenase (BCKADH) via phosphorylation was removed with 0.4 mM alpha-chloroisocaproate (CIC). CIC activated the BCKADH complex 13- to 26-fold and led to increased rates of leucine and valine uptake into muscle, transamination to the corresponding alpha-ketoacid, and leucine (3- to 4-fold) and valine (6-fold) decarboxylation but led to decreased rates of alpha-ketoacid efflux from muscle. Although the increased rates of branched-chain amino acid (BCAA) decarboxylation were extensive, they were far below the extent of BCKADH activation as measured in vitro, suggesting that factors other than BCKADH activation become dominant in controlling the flux through alpha-ketoacid decarboxylation in skeletal muscle in situ. When the BCKADH capacity of muscle was increased 70-90% by a training-induced increase in mitochondrial content, the same 13- to 26-fold activation of the complex by CIC led to a rate of BCAA decarboxylation, which was only marginally greater (10-20%; P less than 0.05) than that of normal muscle. In addition, increasing the energy demand via muscle contractions led to a significant increase in leucine decarboxylation in the presence of complete activation of BCKADH by dephosphorylation. Thus BCKADH phosphorylation-dephosphorylation plays an important though not exclusive role in modulating the rates of BCAA metabolism in skeletal muscle. Differences in valine and leucine metabolism were apparent as valine catabolism bolstered citric acid cycle contents by increasing malate in red muscle with high mitochondrial content.(ABSTRACT TRUNCATED AT 250 WORDS)
Hood
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DA
Department of Physiology, State University of New York-Health Science Center, Syracuse 13210.
Terjung
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RL
D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide); D000597:Amino Acids, Branched-Chain / Q000378:metabolism*; D000818:Animals; D002208:Caproates / Q000494:pharmacology; D003653:Decarboxylation; D006843:Hydrocarbons, Chlorinated; D007658:Ketone Oxidoreductases / Q000378:metabolism*; D007930:Leucine / Q000378:metabolism; D008297:Male; D009097:Multienzyme Complexes / Q000378:metabolism*; D009119:Muscle Contraction; D009132:Muscles / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D011919:Rats, Inbred Strains; D014633:Valine / Q000378:metabolism
D000597:Amino Acids, Branched-Chain; D002208:Caproates; D006843:Hydrocarbons, Chlorinated; D009097:Multienzyme Complexes; C036533:2-chloroisocaproic acid; D007658:Ketone Oxidoreductases; D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide); D007930:Leucine; D014633:Valine