Rat liver microsomal cholesterol biosynthesis and drug oxidase activity are affected by chromium ions (Cr3+) in vitro.
Chromium ions (Cr3+)evoked a biphasic curve of changes of rat liver microsomal cholesterol biosynthesis using [14C]acetate and/or [14C]mevalonate as precursors. While for the lower range of Cr3+ concentrations the rate of cholesterol biosynthesis rises, at concentrations above 8 X 10(-6) M they evoke a decrease in the cholesterol biosynthesis, up to 50% down on its control value at a concentration of 8 X 10(-4) M. Differences were more pronounced when using [14C]mevalonate instead of [14C]acetate as precursor. The activity of the microsomal enzyme biphenyl-4-hydroxylase showed an equally intense rise to that of cholesterol biosynthesis up to a 8 X 10(-6) M Cr3+ concentration. Above this concentration, however, the activity of the enzyme starts to drop. NADPH-cytochrome c reductase and NADPH-oxidase were decreased at all Cr3+ concentrations used, which cover a 100-fold range. Lineweaver-Burk plots of the cytoplasmic glucose-6-phosphate dehydrogenase demonstrated an uncompetitive mechanism of inhibition by Cr3+ ions. The results are discussed in terms of the possible significance of the Cr3+ concentration-dependent effects on cholesterol biosynthesis, with the observed atherosclerosis in Cr-deficient humans.
D000085:Acetates / Q000378:metabolism; D019342:Acetic Acid; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism*; D002250:Carbon Radioisotopes; D002712:Chlorides; D002784:Cholesterol / Q000096:biosynthesis*; D002857:Chromium / Q000494:pharmacology*; D017608:Chromium Compounds; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D007700:Kinetics; D008798:Mevalonic Acid / Q000378:metabolism; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism*; D019255:NADPH Oxidases; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism*; D051381:Rats
D000085:Acetates; D002250:Carbon Radioisotopes; D002712:Chlorides; D017608:Chromium Compounds; D002857:Chromium; D002784:Cholesterol; C017133:chromous chloride; D005954:Glucosephosphate Dehydrogenase; D001189:Aryl Hydrocarbon Hydroxylases; C019793:biphenyl-4-hydroxylase; D009247:NADH, NADPH Oxidoreductases; D009251:NADPH-Ferrihemoprotein Reductase; D019255:NADPH Oxidases; D019342:Acetic Acid; D008798:Mevalonic Acid