Glucocorticoid-mediated activation of muscle branched-chain alpha-keto acid dehydrogenase in vivo.
Muscle branched-chain alpha-keto acid dehydrogenase, the rate-limiting enzyme for branched-chain amino acid oxidation in skeletal muscle, was measured after treatment of rats with glucocorticoids. Cortisone treatment (10 mg X 100 g body wt-1 X day-1 for 2-5 days) resulted in an approximate doubling of the percentage of active enzyme. To further characterize this effect, the enzyme complex was measured 4 h after the intraperitoneal injection of 6 alpha-methylprednisolone, a water-soluble glucocorticoid with rapid onset effects. The percentage of active enzyme increased linearly as the dose of methylprednisolone was increased from 0.125 to 12.5 mg/100 g body wt, while total enzyme activity was unchanged. Administration of insulin with glucose had no significant effect on the activity of the enzyme. However, treatment of rats with insulin and glucose after methylprednisolone administration partially blocked branched-chain alpha-keto acid dehydrogenase activation. The activity of the enzyme complex was correlated with the concentration of leucine in plasma and muscle. Activation of skeletal muscle branched-chain alpha-keto acid dehydrogenase by increased glucocorticoids may play a role in the acceleration of branched-chain amino acid oxidation observed during severe stress.
D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide); D000255:Adenosine Triphosphate / Q000494:pharmacology; D000315:Adrenalectomy; D000597:Amino Acids, Branched-Chain / Q000378:metabolism; D000818:Animals; D003348:Cortisone / Q000031:analogs & derivatives / Q000494:pharmacology; D004492:Edetic Acid / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005459:Fluorides / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology; D007658:Ketone Oxidoreductases / Q000378:metabolism*; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D008776:Methylprednisolone Hemisuccinate / Q000494:pharmacology; D009097:Multienzyme Complexes / Q000378:metabolism*; D009132:Muscles / Q000201:enzymology*; D051381:Rats
D000597:Amino Acids, Branched-Chain; D005938:Glucocorticoids; D007328:Insulin; D009097:Multienzyme Complexes; D008776:Methylprednisolone Hemisuccinate; D000255:Adenosine Triphosphate; D004492:Edetic Acid; D007658:Ketone Oxidoreductases; D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide); D008274:Magnesium; D005459:Fluorides; D003348:Cortisone