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

• Published in: The Journal of biological chemistry Vol. 257; no. 3; pp. 1412 - 1417
• Main Authors: R B Verdery, 3rd, R Theolis, Jr
• Format: Journal Article
• Language: English
• Published: United States American Society for Biochemistry and Molecular Biology 10-02-1982
• Subjects: Acetates - metabolism; Cholesterol - biosynthesis; Fatty Acids - biosynthesis; Fibroblasts - drug effects; Fibroblasts - metabolism; Humans; Hypercholesterolemia - metabolism; Kinetics; Lipoproteins - blood; Lipoproteins, HDL - pharmacology; Lipoproteins, LDL - metabolism; Lipoproteins, LDL - pharmacology; Male; Receptors, Cell Surface - metabolism; Receptors, LDL; Skin - metabolism; Sphingomyelins - biosynthesis
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(19)68208-6

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.