AJP - Endocrinology and Metabolism, Vol 261, Issue 5 E628-E634, Copyright © 1991 by American Physiological Society
Effect of alpha-ketoacid dehydrogenase phosphorylation on branched-chain amino acid metabolism in muscle
D. A. Hood and R. L. Terjung
Department of Physiology, State University of New York-Health Science Center, Syracuse 13210.
The regulation of leucine and valine metabolism was evaluated in skeletal
muscle of perfused rat hindlimb. Control of the branched-chain
alpha-ketoacid dehydrogenase (BCKADH) via phosphorylation was removed with
0.4 mM alpha-chloroisocaproate (CIC). CIC activated the BCKADH complex 13-
to 26-fold and led to increased rates of leucine and valine uptake into
muscle, transamination to the corresponding alpha-ketoacid, and leucine (3-
to 4-fold) and valine (6-fold) decarboxylation but led to decreased rates
of alpha-ketoacid efflux from muscle. Although the increased rates of
branched-chain amino acid (BCAA) decarboxylation were extensive, they were
far below the extent of BCKADH activation as measured in vitro, suggesting
that factors other than BCKADH activation become dominant in controlling
the flux through alpha-ketoacid decarboxylation in skeletal muscle in situ.
When the BCKADH capacity of muscle was increased 70-90% by a
training-induced increase in mitochondrial content, the same 13- to 26-fold
activation of the complex by CIC led to a rate of BCAA decarboxylation,
which was only marginally greater (10-20%; P less than 0.05) than that of
normal muscle. In addition, increasing the energy demand via muscle
contractions led to a significant increase in leucine decarboxylation in
the presence of complete activation of BCKADH by dephosphorylation. Thus
BCKADH phosphorylation-dephosphorylation plays an important though not
exclusive role in modulating the rates of BCAA metabolism in skeletal
muscle. Differences in valine and leucine metabolism were apparent as
valine catabolism bolstered citric acid cycle contents by increasing malate
in red muscle with high mitochondrial content.(ABSTRACT TRUNCATED AT 250
WORDS)
