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Differential control of the cholesterol biosynthetic pathway in tumor versus liver: evidence for decontrolled tumor cholesterogenesis in a cell-free system

Thesis/Dissertation ·
OSTI ID:6152353
Cholesterol biosynthesis was characterized in cell-free post-mitochondrial supernatant (PMS) systems prepared from both normal rat liver and Morris hepatoma 3924A. Per cell, the rate of cholesterol synthesis from either /sup 14/C-citrate of /sup 14/-acetate in the hepatoma system was 9-fold greater than that observed in the liver system. Furthermore, the ratio of sterol-to-fatty acid synthesis rates from /sup 14/C-citrate was more than 3-fold greater in the tumor than in the normal liver system. Incubations using radiolabeled acetate and mevalonate have demonstrated the loss of a normally rate-limiting control site within the early portion of the cholesterol biosynthetic pathway in the tumor system. Upon analysis of the steady-state levels of early lipogenic intermediates, the specific site of decontrol in the tumor was identified as the 3-hydroxy-3-methylglutaryl-CoA ..-->.. mevalonate site of this pathway. In contrast, this reaction appeared to retain its rate-limiting properties in the cell-free system from normal liver.
Research Organization:
New York Univ., NY (USA)
OSTI ID:
6152353
Country of Publication:
United States
Language:
English

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Related Subjects

550201* -- Biochemistry-- Tracer Techniques
550901 -- Pathology-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ACETATES
ANIMAL CELLS
ANIMALS
BIOLOGICAL PATHWAYS
BIOSYNTHESIS
BODY
CARBON 14 COMPOUNDS
CARBOXYLIC ACID SALTS
CHOLESTEROL
CITRATES
DIGESTIVE SYSTEM
DISEASES
GLANDS
HEPATOMAS
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LIVER
MAMMALS
NEOPLASMS
ORGANIC COMPOUNDS
ORGANS
RATS
RODENTS
STEADY-STATE CONDITIONS
STEROIDS
STEROLS
SYNTHESIS
TRACER TECHNIQUES
TUMOR CELLS
VERTEBRATES