Clearing factor, a heparin-activated lipoprotein lipase. I. Isolation and characterization of the enzyme from normal rat heart.

The importance of plasma lipoproteins in normal and abnormal fat metabolism has stimulated interest in the heparin-induced lipemia clearing system first observed by Hahn (2). As a result of the efforts of several independent investigators (3,4), it is now known that,, upon the administrat’ion of heparin to animals of many different species, an enzyme appears in the blood which is able to “clear” lipemic serum in viva or in vitro. It has been difficult to evaluate the role of this “clearing factor” in normal fat metabolism since it normally exists in blood in extremely low concentrations, if at all (5). Certainly the clearing factor content of normal blood is insufficient to account for the rate of disappearance of alimentary lipemia. This is most readily‘evidenced by the fact that lipemic serum does not clear in vitro. Recent investigations of Bragdon and Have1 (6) demonstrated t,hat the administration of prot.amine and other antiheparinoid agents to fasting rats increases the serum lipide and lipoprotein concentration and, when injected simultaneously with lipoproteins, delays their removal. These results suggest that a heparinoid-requiring system is involved in normal fat metabolism. The work to be reported in this paper demonstrates the presence in normal rat heart of an enzyme identical with the clearing factor which appears in blood upon heparin administration. In this and the accompanying paper (7), evidence is presented which supports the view that , clearing factor is a heparin-activated lipoprotein lipase which may play a major role in lipide metabolism.