Branched-chain amino acid metabolism in rat muscle: abnormal regulation in acidosis.
Branched-chain amino acid (BCAA) metabolism is frequently abnormal in pathological conditions accompanied by chronic metabolic acidosis. To study how metabolic acidosis affects BCAA metabolism in muscle, rats were gavage fed a 14% protein diet with or without 4 mmol NH4Cl X 100 g body wt-1 X day-1. Epitrochlearis muscles were incubated with L-[1-14C]-valine and L-[1-14C]leucine, and rates of decarboxylation, net transamination, and incorporation into muscle protein were measured. Plasma and muscle BCAA levels were lower (P less than 0.05) in acidotic rats. Rates of valine and leucine decarboxylation and net transamination were higher (P less than 0.05) in muscles from acidotic rats; these differences were associated with a 79% increase in the total activity of branched-chain alpha-keto acid dehydrogenase and a 146% increase in the activated form of the enzyme. We conclude that acidosis affects the regulation of BCAA metabolism by enhancing flux through the transaminase and by directly stimulating oxidative catabolism through activation of branched-chain alpha-keto acid dehydrogenase.
D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide); D000138:Acidosis / Q000378:metabolism*; D000597:Amino Acids, Branched-Chain / Q000378:metabolism*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D007656:Ketoglutaric Acids / Q000378:metabolism; D007658:Ketone Oxidoreductases / Q000378:metabolism; D008297:Male; D009097:Multienzyme Complexes / Q000378:metabolism; D009132:Muscles / Q000378:metabolism*; D011773:Pyruvates / Q000378:metabolism; D019289:Pyruvic Acid; D051381:Rats; D011919:Rats, Inbred Strains
D000597:Amino Acids, Branched-Chain; D007656:Ketoglutaric Acids; D009097:Multienzyme Complexes; D011773:Pyruvates; D019289:Pyruvic Acid; D007658:Ketone Oxidoreductases; D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)