The fate of arachidonic acid and linoleic acid in isolated working rat hearts containing normal or elevated levels of coenzyme A.
If myocardial levels of coenzyme A (CoA) are elevated, an increase in the rate of esterification of palmitate into myocardial triacylglycerols will occur. In this study, we determined the fate of linoleic acid and arachidonic acid in isolated working rat hearts containing normal or elevated levels of CoA. In hearts containing normal levels of CoA, oxidative rates (measured as 14CO2 production) of [14C]arachidonic acid were significantly lower than those of [14C]palmitic acid, whereas a significantly greater incorporation of [14C]arachidonic acid into myocardial neutral lipids (comprised predominantly of triacylglycerols) was seen when compared to hearts perfused with [14C]palmitic acid. In a second series of hearts, myocardial CoA levels were elevated by perfusing hearts with no carbon substrate, 15 microM pantothenate, 0.5 mM cysteine and 1 mM dithiothreitol, resulting in an increase in myocardial CoA levels from 553 +/- 2 to 918 +/- 63 nmol/g dry wt. Subsequent perfusion of hearts containing elevated CoA levels with 1.2 mM [3H]arachidonic acid or [14C]linoleic acid resulted in a significant increase in incorporation of both these fatty acids into myocardial neutral lipids compared to control hearts. Incorporation of these fatty acids into phospholipids was significantly lower than their incorporation into neutral lipids and was not affected by myocardial CoA levels. Linoleic acid oxidation was unaffected by increases in myocardial levels of CoA. If linoleic acid oxidation was inhibited by adding 5 mM pyruvate to the perfusate, no effect on the incorporation of [14C]linoleic acid into neutral lipids was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
Saddik
M
M
Department of Pediatrics, University of Alberta, Edmonton, Canada.
Lopaschuk
G D
GD
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D003065:Coenzyme A / Q000096:biosynthesis / Q000378:metabolism*; D007700:Kinetics; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010084:Oxidation-Reduction; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D008041:Linoleic Acids; D010169:Palmitic Acids; D016718:Arachidonic Acid; D019308:Palmitic Acid; D019787:Linoleic Acid; D003065:Coenzyme A