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Sphingolipid Biosynthesis by Rat Liver Cells: Effects of Serine, Fatty Acids and Lipoproteins^1,2,

Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322

The effects of circulating factors that might influence de novo sphingolipid biosynthesis were examined with rat liver cells by following the incorporation of [¹⁴C]serine into sphingosine and sphinganine, the predominant long-chain base backbones of hepatic sphingolipids. The rate of long-chain base formation depended on the concentration of [¹⁴C]serine in the medium and exhibited saturation kinetics. Long-chain base formation was stimulated by another precursor, palmitic acid, but stearic, oleic, linoleic and linolenic acids were inhibitory. This kinetic behavior indicates that long-chain base formation in liver is affected by the availability of the substrates of the initial enzyme of this pathway, serine palmitoyltransferase. Since liver is also exposed to sphingolipids associated with circulating lipoproteins, the effects of various lipoprotein fractions were determined and each appeared to decrease long-chain base formation. These results suggest that hepatic long-chain base biosynthesis can be stimulated by increases in the circulating levels of the precursors serine and palmitic acid whereas some other fatty acids and lipoproteins decrease the flux through this pathway.

KEY WORDS: • sphingolipids • serine • palmitic acid • lipoproteins • cholesterol • liver • biosynthesis

¹ Supported by National Institutes of Health grant GM33369, and by funds from the Georgia affiliate of the American Heart Association.

² Presented in part at the 1986 Annual Meeting of the Federation of the American Societies for Experimental Biology, St. Louis, MO, April 13–18, 1986 [MESSMER, T. & MERRILL, A. H., JR. (1986) Substrate availability for long-chain base formation as a regulator of hepatic sphingolipid and cholesterol biosynthesis. Fed. Proc. 45: 842 (abs. 4001)].

³ Present address: Department of Dermatology, Emory University.

⁴ To whom reprint requests should be addressed.

Manuscript received 24 March 1988. Revision accepted 7 December 1988.