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Carnitine effects on coenzyme A profiles in rat liver with hypoglycin inhibition of multiple dehydrogenases
Ist Teil von
American journal of physiology: endocrinology and metabolism, 1997-03, Vol.272 (3), p.E359-E366
Ort / Verlag
United States
Erscheinungsjahr
1997
Quelle
MEDLINE
Beschreibungen/Notizen
Y. K. Lieu, B. Y. Hsu, W. A. Price, B. E. Corkey and C. A. Stanley
Division of Endocrinology/Diabetes, The Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, 19104, USA.
To examine the changes in coenzyme A profile and the possible corrective
effects of carnitine supplementation in the genetic disorders of
mitochondrial beta-oxidation, we carried out experiments 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 branched-chain fatty acids (alpha-ketoisocaproate) with a parallel
70-90% reduction of hepatocyte acetyl-CoA levels. Alone, MCPA or substrates
halved free CoA levels to 15% of total CoA and doubled short- and
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- and
medium-chain acyl-CoA levels were 45% of total CoA. Comparable changes in
CoA profiles were found in a patient with a severe genetic defect in
beta-oxidation. Neither the suppression of ketogenesis nor the alterations
in CoA profiles induced by MCPA inhibition could be corrected by carnitine
supplementation.