Heparin-bound lipoprotein lipase is catalytically active and can be stimulated by apolipoprotein CII

Abstract

Lipoprotein lipase hydrolyses acylglycerols in chylomicrons and very low density lipoproteins at the vascular endothelium [l]. It has been proposed that the enzyme is held in place there via interaction with a heparin-like polyanion; e.g., heparan sulphate [2]. This theory has gained support from studies showing that enzymatic digestion of the heparan sulphate chains on cultured endothelial cell impedes the binding of lipoprotein lipase to the cells [3,4]. Lipoprotein lipase readily binds heparin [5]; this stabilizes the enzyme [6] and makes it more soluble [7]. However, heparin seems to have little or no effect on the catalytic activity of lipoprotein lipase. This is true both in crude systems with very low density lipoproteins as the substrate [8] and with triglyceride emulsions [9]. Since the heparin molecule has a strong negative charge and specifically affects the activity of several enzymes in the coagulation cascade the lack of effect on lipoprotein lipase was somewhat surprising. There were two possible explanations: (i) Binding of heparin does not affect the function of those regions of the lipase molecule which are involved in catalysis; or (ii) The complex between heparin and lipoprotein lipase dissociates when the enzyme binds to a lipoprotein. In support of (ii), there is a report that apolipoprotein CII, the activator protein for lipoprotein lipase, and heparin compete for binding to the enzyme [lo]. It was therefore important to investigate directly the relation between binding of the enzyme to heparin and its ability to carry out the catalytic reaction. We report here that lipoprotein lipase can hydrolyze acylglycerols while bound to heparin-Sepharose and that