AJP - Heart and Circulatory Physiology, Vol 253, Issue 1 41-H46, Copyright © 1987 by American Physiological Society
Stimulation of myocardial coenzyme A degradation by fatty acids
G. D. Lopaschuk and J. R. Neely
Coenzyme A (CoA) levels were increased in isolated hearts from 537 +/- 14
to 818 +/- 44 nmol/g dry wt by perfusion for 45 min under conditions known
to stimulate CoA synthesis (5). Subsequently, perfusion of these hearts
with buffer containing glucose (11 mM) and pyruvate (5 mM) for 3 min had no
effect on CoA levels (789 +/- 42 nmol/g dry wt). However, perfusion with a
buffer containing glucose (11 mM) and palmitate (1.2 mM) decreased CoA
levels to 683 +/- 34 nmol/g dry wt within 3 min. This decrease in CoA
appeared to occur in the cytosolic compartment with no change in
mitochondrial CoA content and was associated with a rise in tissue content
of long-chain acyl-CoA. An increased incorporation of fatty acids into
triglycerides was associated with the rise in total acyl-CoA suggesting
that long-chain acyl-CoA levels were elevated in the cytosolic compartment.
Perfusion conditions which maximally increased acyl-CoA levels also
maximally stimulated CoA degradation. These observations suggest that the
cytosolic degradation of CoA is related to high levels of long-chain
acyl-CoA in this compartment. Use of these perfusion conditions in future
studies should help define the pathway of CoA degradation and determine the
mechanisms which control cellular levels of CoA.
