LIPOPROTEIN LIPASE - THE MOLECULE AND ITS INTERACTIONS

Abstract

It is clear from the primary sequences that lipoprotein lipase (LPL)is related to hepatic lipase and to pancreatic lipase. Consideration of sequence homologies and biochemical evidence suggests that the folded structure of LPL may also be similar to that for pancreatic lipase. Both enzymes require small proteins for function in their physiological environment, apolipoprotein CII and colipase, respectively. There is however, no homology between the activators, which probably evolved separately. The lipases are very efficient with turnover numbers for triglyceride hydrolysis in the physiological environment of over 1000 sec" To probe their mode of action we have compared hydrolysis of triglycerides and phospholipids in mixed liposomes and in emulsions. Binding oflipase to the two types of particles was similar. Yet, triglyceride hydrolysis was more than 10 times more rapid and the ratio of triglyceride to phospholipid hydrolysis was more than 50-fold higher with the emulsion droplets than with the liposomes. This suggests that the route of substrate entry into the active site is from below, and that the lipase stays at the interface for several rounds oflipolysis. This would seem to fit well with the x-ray structure of pancreatic lipase, which shows the active site at the bottom of a cleft. Lipoprotein lipase (LPL) is member of a protein family which also includes hepatic lipase and pancreatic lipase. The three lipases are engaged in different aspects oflipid transport and serve basically similar functions. They hydrolyze triglycerides to fatty acids and monoglycerides which can be taken up by cells for use in metabolic reactions, or be packaged for further transport.