Leucine and isoleucine activate skeletal muscle branched-chain alpha-keto acid dehydrogenase in vivo.
The response of rat skeletal muscle branched-chain alpha-keto acid dehydrogenase to administration of branched-chain amino acids in vivo was determined using a soluble preparation of the enzyme. After detergent extraction of the complex in the presence of kinase and phosphatase inhibitors, initial in vivo activity was typically 1 nmol X min-1 X g muscle-1, with 0.1 mM alpha-[1-14C]ketoisocaproate as substrate. Total activity of the dephosphorylated complex, measured after preincubation with 15 mM Mg2+, typically reached a maximum of 29 nmol X min-1 X g-1. Thus in overnight-fasted rats the complex was 2-3% active. Initial activity increased three- to fivefold after leucine or isoleucine (at higher concentrations) but not valine administration in vivo. After intravenous leucine injection (0.25 mmol/kg) initial muscle enzyme activity increased rapidly and subsequently decreased, paralleling plasma leucine concentrations, while plasma valine and isoleucine decreased. In conclusion, muscle branched-chain alpha-keto acid dehydrogenase complex is rapidly activated when circulating leucine is increased to concentrations that may occur after meals. During hyperleucinemia accelerated valine and isoleucine degradation by muscle may account for the observed "antagonism" among the branched-chain amino acids.
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D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide); D000818:Animals; D004789:Enzyme Activation / Q000187:drug effects; D007532:Isoleucine / Q000097:blood / Q000494:pharmacology*; D007658:Ketone Oxidoreductases / Q000378:metabolism*; D007700:Kinetics; D007930:Leucine / Q000097:blood / Q000494:pharmacology*; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D009097:Multienzyme Complexes / Q000378:metabolism*; D009132:Muscles / Q000201:enzymology*; D051381:Rats; D011919:Rats, Inbred Strains; D014633:Valine / Q000097:blood / Q000494:pharmacology
D009097:Multienzyme Complexes; D007532:Isoleucine; D007658:Ketone Oxidoreductases; D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide); D007930:Leucine; D014633:Valine; D008274:Magnesium