AJP - Endocrinology and Metabolism, Vol 252, Issue 3 E396-E407, Copyright © 1987 by American Physiological Society
Glucocorticoid-mediated activation of muscle branched-chain alpha-keto acid dehydrogenase in vivo
K. P. Block, W. B. Richmond, W. B. Mehard and M. G. Buse
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.
