Inter-relationships between dolichol and sterol synthesis in mammalian cell cultures.
نویسندگان
چکیده
A method is described for the measurement of [‘“Clacetate incorporation into dolichol in cultured mammalian cells. In various cell types, [Wlacetate was incorporated into dolichol at a rate 0.03 to 0.11% of the incorporation rate into sterol. When 2&hydroxycholesterol was added to L cell cultures, [Wlacetate incorporation into both dolichol and sterol decreased in a concentration-dependent manner, although the relationship between the concentration of 25-hydroxycholesterol, and the level of inhibition differed for the two lipids. Comparison of the rates of sterol and dolichol synthesis from acetate indicated that situations may exist in which large fluctuations in sterol synthesis can occur while the rate of dolichol synthesis is only slightly affected. However, under other conditions where sterol synthesis was repressed to levels below approximately 25% of the control level, further decrease in sterol synthesis was accompanied by a proportional decline in dolichol synthesis. The results suggest that 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCoA reductase, EC 1.1.1.34), affects the rate of dolichol synthesis by altering the concentration of a substrate for an enzyme which catalyzes a rate-limiting reaction peculiar to the dolichol branch of the biosynthetic pathway. This conclusion was supported by other studies in which L cells were grown in serum-supplemented medium and 25-hydroxycholesterol was added to MOPC 104E cultures. The data indicate an interaction by which two or more biosynthetic pathways can share common intermediates and a regulatory enzyme while maintaining a large degree of regulatory independence.
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ورودعنوان ژورنال:
- The Journal of biological chemistry
دوره 254 17 شماره
صفحات -
تاریخ انتشار 1979