Defective 3-ketosteroid reductase activity in a human monocyte-like cell line.
The human monocyte-like cell line U937, which is a cholesterol auxotroph, does not grow on mevalonate, squalene, or 4,4-dimethyl cholest-7-en-3 beta-ol. It grows on cholest-7-en-3 beta-ol and converts it to cholesterol. When deprived of an exogenous source of cholesterol, the cells accumulate 4 alpha-methyl-cholest-8-en-3-one. The cell-free extracts of U937 are also devoid of 3-ketoreductase activity. The present studies indicate that the lesion in cholesterol synthesis by these cells is located at 3-ketosteroid reductase, making this the first report of a deficiency of this enzyme. In contrast, another U937 strain (U937-N) synthesizes cholesterol, does not accumulate 4 alpha-methyl-cholest-8-en-3-one, and has 3-ketosteroid reductase activity. The two strains should be valuable in studies of the regulation of cholesterol metabolism and of the role of cholesterol in membrane structure and function.
D015096:3-Hydroxysteroid Dehydrogenases / Q000172:deficiency; D000818:Animals; D002460:Cell Line; D002784:Cholesterol / Q000096:biosynthesis*; D006801:Humans; D066298:In Vitro Techniques; D008264:Macrophages / Q000201:enzymology*; D008862:Microsomes, Liver / Q000201:enzymology; D009000:Monocytes / Q000201:enzymology*; D051381:Rats; D013261:Sterols / Q000378:metabolism
D013261:Sterols; D002784:Cholesterol; D015096:3-Hydroxysteroid Dehydrogenases; C031298:3-ketosteroid reductase