Hormones and triacylglycerol metabolism under normoxic and ischemic conditions.
Fatty acids, the preferred substrate in normoxic myocardium, are derived from either exogenous or endogenous triacylglycerols. The supply of exogenous fatty acids is dependent of the rate of lipolysis in adipose tissue and of the lipoprotein lipase activity at the coronary vascular endothelium. A large part of the liberated fatty acids is reesterified with glycerol-3-phosphate and converted to triacylglycerols. Endogenous lipolysis and lipogenesis are intracellular compartmentalized multienzyme processes of which individual hormone-sensitive steps have been demonstrated in adipose tissue. The triacylglycerol lipase is the rate-limiting enzyme of lipolysis and glycerol-3-phosphate acyltransferase and possibly phosphatidate phosphohydrolase are the rate-limiting enzymes of lipogenesis. The hormonal regulation of both processes in heart is still a matter of dispute. Triacylglycerol lipase activity in myocardial tissue has two intracellular sources: 1. the endoplasmic reticular and soluble neutral lipase, and 2. the lysosomal acid lipase. Studies in our laboratory have indicated that whereas lipolysis is enhanced during global ischemia and anoxia, overall lipolytic enzyme activities in heart homogenates were not altered. In addition we were unable to demonstrate alterations in tissue triacylglycerol content and glycerol-3-phosphate acyltransferase activity under these conditions. Lipolysis, is subject to feedback inhibition by product fatty acids. Therefore all processes leading to an increased removal of fatty acids from the catalytic site of the lipase will stimulate lipolysis. These studies will be reviewed. In addition, studies from our department have demonstrated the capacity of myocardial lysosomes to take up and degrade added triacylglycerol-particles in vitro. Such a process, stimulated by Ca2+ and stimulated by acidosis, offers another physiological target for hormone actions.
Schoonderwoerd
K
K
Department of Biochemistry I, Medical Faculty, Erasmus University Rotterdam, The Netherlands.
van der Kraaij
T
T
Hülsmann
W C
WC
Stam
H
H
D000818:Animals; D003327:Coronary Disease / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism; D008049:Lipase / Q000378:metabolism; D008066:Lipolysis; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism*
D005227:Fatty Acids; D014280:Triglycerides; D008049:Lipase