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Substrate availability for long-chain base formation as a regulator of hepatic sphingolipid and cholesterol biosynthesis

Conference · · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)
OSTI ID:6965996
;

The de novo biosynthesis of the sphinganine and sphingosine backbones of sphingolipids was studied with isolated rat hepatocytes and established liver cell lines. The rate of incorporation of radiolabel from (/sup 14/C)-serine by intact cells was half maximal at 0.3 mM, which is similar to the K/sub m/ of the initial enzyme of this pathway and in vivo concentrations of this substrate. Long-chain base biosynthesis was stimulated by another precursor, palmitic acid, but other fatty acids were inhibitory. Hepatocytes isolated from fed and fasted rats had different rates of sphingolipid formation, which may also reflect the relative levels of palmitoyl-CoA. These results established that the availability of the precursors of long-chain base formation, serine and palmitic acid, is a major factor in the regulation of this pathway. Since sphingomyelin biosynthesis could be modified, its relationship to cholesterol metabolism was also examined. Both hepatocytes and cultured liver cells in high serine (0.6mM) had increased incorporation of (/sup 14/C)-acetate into cholesterol (13%, P < 0.05 and 50%, P < 0.01, respectively). These results indicate that sphingolipid and cholesterol biosynthesis are coordinately regulated, perhaps because these lipids are located in similar membranes and lipoproteins.

Research Organization:
Emory Univ. School of Medicine, Atlanta, GA
OSTI ID:
6965996
Report Number(s):
CONF-8604222-
Journal Information:
Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Vol. 45:4; ISSN FEPRA
Country of Publication:
United States
Language:
English

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Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ACETATES
AMINO ACIDS
ANIMAL CELLS
ANIMALS
BIOLOGICAL PATHWAYS
BIOSYNTHESIS
CARBON 14 COMPOUNDS
CARBOXYLIC ACID SALTS
CARBOXYLIC ACIDS
CHOLESTEROL
FASTING
HYDROXY ACIDS
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LIPIDS
LIVER CELLS
MAMMALS
ORGANIC ACIDS
ORGANIC COMPOUNDS
RATS
RODENTS
SERINE
SOMATIC CELLS
STEROIDS
STEROLS
SYNTHESIS
TRACER TECHNIQUES
VERTEBRATES