5. alpha. -cholest-8(14)-en-3. beta. -ol-15-one. Studies on its metabolism in cultured cells and male baboons. Volume 1 and 2

Miscellaneous · Sun Jan 01 00:00:00 EST 1989

OSTI ID:5475602

Pajewski, T N

5{alpha}-Cholest-8(14)-en-3{beta}-ol-15-one is a potent is a potent inhibitor of cholesterol biosynthesis which has been found to have significant hypocholesterolemic action upon oral administration to rodents and nonhuman primates. The metabolism of (2,4-{sup 3}H)5{alpha}-cholest-8(14)-3n-3{beta}-ol-15-one was studied in Chinese hamster ovary (CHO-K1) cells. The incorporation of the labeled 15-ketosterol into the cells was linear with respect to sterol concentration in the medium over the range of concentrations studied and was higher than the uptake of cholesterol. The results of detailed analyses of the lipids recovered from the cells after 6 hours of incubation with the (2,4-{sup 3}H)-15-ketosterol indicated that most of the {sup 3}H was associated with the free 15-ketosterol. Considerably smaller amounts of {sup 3}H were associated with esters of the 15-ketosterol. No conversion of the 15-ketosterol to cholesterol or other C{sup 27} monohydroxysterols was observed. The labeled material with the chromatographic behavior of esters of the 15-ketosterol gave, after mild saponification, the free 15-ketosterol which was characterized by cocrystallization and chromatographic studies. The metabolism of the 15-ketosterol was also studied in male baboons (Papio cynocephalus) treated with the 15-ketosterol. After oral administration of a mixture of (2,4-{sup 3}H)5{alpha}-cholest-8(14)-en-3{beta}-ol-15-one and (4-{sup 14}C)cholesterol, blood samples were obtained at various times. Marked differences in the time courses of the levels of {sup 3}H and {sup 14}C in plasma were observed. {sup 3}H showed maximum levels at 4 to 8 h, while maximum values for the levels of {sup 14}C were observed much later. Total lipid extraction of plasma showed that essentially all of the {sup 14}C of plasma was recovered in the lipid extract.

• Research Organization: Rice Univ., Houston, TX (United States)
• OSTI ID: 5475602
• Resource Relation: Other Information: Thesis (Ph. D.)
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
CHOLESTEROL
BIOSYNTHESIS
STEROLS
METABOLISM
BABOONS
CARBON 14 COMPOUNDS
CHO CELLS
CHROMATOGRAPHY
INHIBITION
LIPIDS
ORAL ADMINISTRATION
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ANIMAL CELLS
ANIMALS
CARBON COMPOUNDS
HYDROGEN COMPOUNDS
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
MONKEYS
ORGANIC COMPOUNDS
PRIMATES
SEPARATION PROCESSES
STEROIDS
SYNTHESIS
VERTEBRATES
550501* - Metabolism- Tracer Techniques