Cholesterol, 7-ketocholesterol and 25-hydroxycholesterol uptake studies and effect on 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity in human fibroblasts.
Biological-Transport, Cells-Cultured, Cholesterol: aa, me, Culture-Media, Fibroblasts: de, me, Human, Hydroxycholesterols: me, Hydroxymethylglutaryl-CoA-Reductases: ai, Infant-Newborn, Ketosteroids: me, Kinetics, Lipoproteins, Male, SUPPORT-U-S-GOVT-P-H-S, Thermodynamics, Time-Factors
Biochim-Biophys-Acta. 1975 Jul 22; 398(1):10-7.
In human fibroblasts two oxidized derivatives of cholesterol, 7-ketocholesterol and 25-hydroxycholesterol, but not cholesterol itself, are potent inhibitors of 3-hydroxy-3-methylglutaryl co-enzyme A reductase (mevalonate: NADP+ oxidoreductase (Co-enzyme A acylating), (EC 188.8.131.52), the rate-limiting enzyme in sterol biosynthesis. In addition, these derivatives of cholesterol are effective regulators in cells from homozygous familial hypercholesterolemic individuals. The differences in the inhibitory potencies of the sterols cannot be explained in terms of the amount of uptake into the cell.
Breslow, J L.; Lothrop, D A.; Spaulding, D R.; and Kandutsch, A A., " Cholesterol, 7-ketocholesterol and 25-hydroxycholesterol uptake studies and effect on 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity in human fibroblasts." (1975). Faculty Research 1970 - 1979. 556.
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