Regulation of sphingomyelin long chain base synthesis in human fibroblasts in culture. Role of lipoproteins and the low density lipoprotein receptor

Abstract

We have studied regulation of synthesis of long chain bases in human fibroblasts using 3 different radioactive precursors and 2 different hydrolysis and separation procedures. Serum and low density lipoproteins inhibited synthesis. Inhibition of long chain base synthesis by various concentrations of low density lipoproteins paralleled inhibition of cholesterol synthesis. This inhibition was dependent on the low density lipoprotein receptor pathway since fibroblasts from homozygous familial hypercholesterolemic patients did not show the inhibition observed with normal fibroblasts. Incorporation of precursor palmitate into free or total long chain bases was inhibited by low density lipoproteins to the same extent as incorporation into sphingomyelin long chain bases. We thus propose that an enzyme in the pathway leading to sphinganine synthesis, probably palmitoyl-CoA:L-serine C-palmitoyltransferase (decarboxylating) EC 2.3.1.50, is regulated by low density lipoproteins.