Biogenesis of plasma membrane cholesterol

Conference · Thu May 01 04:00:00 EDT 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:5272203

Lange, Y

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.

• Research Organization: Rush Medical College, Chicago, IL
• OSTI ID: 5272203
• Report Number(s): CONF-8606151-
• Conference Information: Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Journal Volume: 45:6
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ACETATES
ANIMAL CELLS
ANIMALS
BIOLOGICAL HALF-LIFE
BIOLOGICAL MATERIALS
BIOLOGICAL PATHWAYS
BIOSYNTHESIS
BLOOD
BLOOD PLASMA
BODY FLUIDS
CARBOXYLIC ACID SALTS
CELL CONSTITUENTS
CELL MEMBRANES
CENTRIFUGATION
CHEMICAL COMPOSITION
CHOLESTEROL
CONNECTIVE TISSUE CELLS
ENDOPLASMIC RETICULUM
ENZYMES
FIBROBLASTS
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
MAN
MATERIALS
MEMBRANES
MOLECULAR STRUCTURE
ORGANIC COMPOUNDS
ORGANOIDS
OXIDOREDUCTASES
PRIMATES
SEPARATION PROCESSES
SOMATIC CELLS
STEROIDS
STEROLS
SYNTHESIS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES