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Title: Biogenesis of plasma membrane cholesterol

Abstract

A striking feature of the molecular organization of eukaryotic cells is the singular enrichment of their plasma membranes in sterols. The authors studies are directed at elucidating the mechanisms underlying this inhomogeneous disposition. Cholesterol oxidase catalyzes the oxidation of plasma membrane cholesterol in intact cells, leaving intracellular cholesterol pools untouched. With this technique, the plasma membrane was shown to contain 95% of the unesterified cholesterol of cultured human fibroblasts. Cholesterol synthesized from (/sup 3/H) acetate moved to the plasma membrane with a half-time of 1 h at 37/sup 0/C. They used equilibrium gradient centrifugation of homogenates of biosynthetically labeled, cholesterol oxidase treated cells to examine the distribution of newly synthesized sterols among intracellular pools. Surprisingly, lanosterol, a major precursor of cholesterol, and intracellular cholesterol both peaked at much lower buoyant density than did 3-hydroxy-3-methylglutaryl-CoA reductase. This suggests that cholesterol biosynthesis is not taken to completion in the endoplasmic reticulum. The cholesterol in the buoyant fraction eventually moved to the plasma membrane. Digitonin treatment increased the density of the newly synthesized cholesterol fractions, indicating that nascent cholesterol in transit is associated with cholesterol-rich membranes. The authors are testing the hypothesis that the pathway of cholesterol biosynthesis is spatially organized in variousmore » intracellular membranes such that the sequence of biosynthetic steps both concentrates the sterol and conveys it to the plasma membrane.« less

Authors:
Publication Date:
Research Org.:
Rush Medical College, Chicago, IL
OSTI Identifier:
5272203
Report Number(s):
CONF-8606151-
Journal ID: CODEN: FEPRA; TRN: 86-031453
Resource Type:
Conference
Journal Name:
Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)
Additional Journal Information:
Journal Volume: 45:6; Conference: 76. annual meeting of the Federation of American Society for Experimental Biology, Washington, DC, USA, 8 Jun 1986
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; CELL MEMBRANES; CHEMICAL COMPOSITION; CHOLESTEROL; BIOSYNTHESIS; ACETATES; BIOLOGICAL HALF-LIFE; BIOLOGICAL PATHWAYS; BLOOD PLASMA; CENTRIFUGATION; ENDOPLASMIC RETICULUM; FIBROBLASTS; MAN; MOLECULAR STRUCTURE; OXIDOREDUCTASES; TRACER TECHNIQUES; TRITIUM COMPOUNDS; ANIMAL CELLS; ANIMALS; BIOLOGICAL MATERIALS; BLOOD; BODY FLUIDS; CARBOXYLIC ACID SALTS; CELL CONSTITUENTS; CONNECTIVE TISSUE CELLS; ENZYMES; HYDROXY COMPOUNDS; ISOTOPE APPLICATIONS; LABELLED COMPOUNDS; MAMMALS; MATERIALS; MEMBRANES; ORGANIC COMPOUNDS; ORGANOIDS; PRIMATES; SEPARATION PROCESSES; SOMATIC CELLS; STEROIDS; STEROLS; SYNTHESIS; VERTEBRATES; 550201* - Biochemistry- Tracer Techniques

Citation Formats

Lange, Y. Biogenesis of plasma membrane cholesterol. United States: N. p., 1986. Web.
Lange, Y. Biogenesis of plasma membrane cholesterol. United States.
Lange, Y. Thu . "Biogenesis of plasma membrane cholesterol". United States.
@article{osti_5272203,
title = {Biogenesis of plasma membrane cholesterol},
author = {Lange, Y},
abstractNote = {A striking feature of the molecular organization of eukaryotic cells is the singular enrichment of their plasma membranes in sterols. The authors studies are directed at elucidating the mechanisms underlying this inhomogeneous disposition. Cholesterol oxidase catalyzes the oxidation of plasma membrane cholesterol in intact cells, leaving intracellular cholesterol pools untouched. With this technique, the plasma membrane was shown to contain 95% of the unesterified cholesterol of cultured human fibroblasts. Cholesterol synthesized from (/sup 3/H) acetate moved to the plasma membrane with a half-time of 1 h at 37/sup 0/C. They used equilibrium gradient centrifugation of homogenates of biosynthetically labeled, cholesterol oxidase treated cells to examine the distribution of newly synthesized sterols among intracellular pools. Surprisingly, lanosterol, a major precursor of cholesterol, and intracellular cholesterol both peaked at much lower buoyant density than did 3-hydroxy-3-methylglutaryl-CoA reductase. This suggests that cholesterol biosynthesis is not taken to completion in the endoplasmic reticulum. The cholesterol in the buoyant fraction eventually moved to the plasma membrane. Digitonin treatment increased the density of the newly synthesized cholesterol fractions, indicating that nascent cholesterol in transit is associated with cholesterol-rich membranes. The authors are testing the hypothesis that the pathway of cholesterol biosynthesis is spatially organized in various intracellular membranes such that the sequence of biosynthetic steps both concentrates the sterol and conveys it to the plasma membrane.},
doi = {},
journal = {Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)},
number = ,
volume = 45:6,
place = {United States},
year = {1986},
month = {5}
}

Conference:
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