Carnitine effects on coenzyme a profiles in rat liver with
hypoglycin inhibition of multiple dehydrogenases.
Lieu, Yen K., Betty Y. L. Hsu, William A. Price, Barbara E. Corkey,
Charles A. Stanley.
Division of Endocrinology/Diabetes, The Children's Hospital of
Philadelphia, University of Pennsylvania School of Medicine,
Philadelphia, PA 19104; Department of Chemistry and Biochemistry,
LaSalle University, Philadelphia, PA 19141; Diabetes and Metabolism
Unit, Boston University School of Medicine, Boston, MA 02118
APStracts 3:0227E, 1996.
To examine the changes in coenzyme A profile and the possible
corrective effects of carnitine supplementation in the genetic
disorders of mitochondrial -oxidation, experiments were carried out
using an inhibitor of multiple acyl-CoA dehydrogenase enzymes,
methylenecyclopropaneacetic acid (MCPA), in rat hepatocytes. MCPA
irreversibly inhibited ketone synthesis from straight-chain fatty
acids (butyrate, octanoate, palmitate) and branch-chain fatty acids
(a-ketoisocaproate) with a parallel 70-90% reduction of hepatocyte
acetyl-CoA levels. Alone, MCPA or substrates halved free coenzyme A
levels to 15% of total CoA and doubled short & medium-chain acyl-CoA
levels to 30% of total CoA. With MCPA plus substrates combined, free
CoA levels were 10% of total CoA and short & medium-chain acyl-CoA
levels were 45% of total CoA. Comparable changes in coenzyme A
profiles were found in a patient with a severe genetic defect in
-oxidation. Neither the suppression of ketogenesis nor the alterations
in coenzyme A profiles induced by MCPA inhibition could be corrected
by carnitine supplementation.
Received 15 July 1996; accepted in final form 30 October 1996.
APS Manuscript Number E334-6.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 13 November 1996