Control of Lipid Metabolism in Human Leukocytes

Abstract

Abstract Human leukocytes were incubated for 6 hours in full or lipid-free serum with either [2-14C]acetate or [2-14C]mevalonate, with and without cycloheximide. There was a marked enhancement of incorporation of [2-14C]acetate but not [2-14C]mevalonate into sterols when lipid-free sera were used. The increased incorporation was partially inhibited by 2.0 µm cycloheximide and completely inhibited by 10 µm. The basal incorporation of [2-14C]acetate and [2-14C]mevalonate was not affected by the cycloheximide. The data are interpreted as proof that an enzyme preceding those acting on mevalonate was induced in the cells incubated in the lipid-free sera. It was found that six hypercholesterolemic individuals with type II lipoprotein patterns could not be distinguished from nine normals by the radioactivity incorporated into sterols by their leukocytes from [2-14C]acetate or [2-14C]mevalonate. However, the ratio of radioactivity incorporated from [2-14C]acetate in lipid-free serum to that incorporated in full serum was higher for the hypercholesterolemics than for the normals (3.02 ± 0.12 versus 1.99 ± 0.06; p l 0.001). The data indicate that, irrespective of the basal level of incorporation, the cells of hypercholesterolemics show an exaggerated response to the lipid-free serum.