Interaction of various metabolites and agents with branched-chain 2-oxo acid oxidation in rat and human muscle in vitro.
The interaction of various metabolites and agents with the 14CO2 production from 0.1 mM [1-14C]-labelled 2-oxoisocaproate (KIC) and 2-oxoisovalerate (KIV) was studied in rat and human heart and skeletal muscle preparations. Glucose and carnitine had no effect in any of the studied systems; palmitate gave a small increase of KIC oxidation only in soleus muscle. With rat hemidiaphragms a considerable decrease was found in the presence of high concentrations of a competitive branched-chain 2-oxo acid and of pyruvate, and in the presence of ketone bodies. A considerable increase was found in the presence of the branched-chain 2-oxo acid dehydrogenase kinase inhibitor 2-chloroisocaproate and the transminase inhibitor amino-oxyacetate. 2-Oxoglutarate increased and clofibric acid decreased only KIC oxidation. Divergent effects were given by intermediates of the degradation route of KIC and KIV and by monocarboxylate translocator inhibitors. The observed interactions are discussed and related to regulatory mechanisms which are known to affect the branched-chain 2-oxo acid dehydrogenase complex.
D000597:Amino Acids, Branched-Chain / Q000378:metabolism; D000818:Animals; D002331:Carnitine / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007651:Keto Acids / Q000378:metabolism*; D008297:Male; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D010084:Oxidation-Reduction; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000494:pharmacology; D051381:Rats
D000597:Amino Acids, Branched-Chain; D007651:Keto Acids; D010169:Palmitic Acids; D019308:Palmitic Acid; D005947:Glucose; D002331:Carnitine