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

Abstract

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.

Authors:
;
Publication Date:
Research Org.:
Emory Univ. School of Medicine, Atlanta, GA
OSTI Identifier:
6965996
Report Number(s):
CONF-8604222-
Journal ID: CODEN: FEPRA; TRN: 87-005731
Resource Type:
Conference
Journal Name:
Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)
Additional Journal Information:
Journal Volume: 45:4; Conference: 70. annual meeting of the Federation of American Society for Experimental Biology, St. Louis, MO, USA, 13 Apr 1986
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; CHOLESTEROL; BIOSYNTHESIS; LIPIDS; ACETATES; BIOLOGICAL PATHWAYS; CARBON 14 COMPOUNDS; CARBOXYLIC ACIDS; FASTING; LIVER CELLS; RATS; SERINE; TRACER TECHNIQUES; AMINO ACIDS; ANIMAL CELLS; ANIMALS; CARBOXYLIC ACID SALTS; HYDROXY ACIDS; HYDROXY COMPOUNDS; ISOTOPE APPLICATIONS; LABELLED COMPOUNDS; MAMMALS; ORGANIC ACIDS; ORGANIC COMPOUNDS; RODENTS; SOMATIC CELLS; STEROIDS; STEROLS; SYNTHESIS; VERTEBRATES; 550201* - Biochemistry- Tracer Techniques

Citation Formats

Messmer, T O, and Merrill, Jr, A H. Substrate availability for long-chain base formation as a regulator of hepatic sphingolipid and cholesterol biosynthesis. United States: N. p., 1986. Web.
Messmer, T O, & Merrill, Jr, A H. Substrate availability for long-chain base formation as a regulator of hepatic sphingolipid and cholesterol biosynthesis. United States.
Messmer, T O, and Merrill, Jr, A H. Wed . "Substrate availability for long-chain base formation as a regulator of hepatic sphingolipid and cholesterol biosynthesis". United States.
@article{osti_6965996,
title = {Substrate availability for long-chain base formation as a regulator of hepatic sphingolipid and cholesterol biosynthesis},
author = {Messmer, T O and Merrill, Jr, A H},
abstractNote = {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.},
doi = {},
journal = {Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)},
number = ,
volume = 45:4,
place = {United States},
year = {1986},
month = {3}
}

Conference:
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