Biosynthesis of squalene and cholesterol by cell-free extracts of adult rat brain.
Cell-free extracts of adult rat brain incubated with mevalonic acid-2-(14)C synthesize (14)C-labeled nonsaponifiable fractions consisting largely of squalene-(14)C. If the cofactor concentrations of the incubation medium are adjusted, much of the squalene can be induced to undergo turnover, with a resultant increase in (14)C-labeled digitonin-precipitable sterols, which include a small amount of cholesterol. The synthesis of labeled sterols is markedly increased in the presence of Mg(++) and depressed by nicotinamide. ATP, NADH, GSH, and glucose-6-phosphate are required for optimal synthesis of digitonin-precipitable material but, unlike Mg(++), are not essential. The cofactor-adjusted extracts also synthesize a complex ester mixture containing, in addition to cholesterol-(14)C, several compounds less polar than cholesterol. The biosynthesis of cholesterol in the extracts is a slow process; at least 12 hr of incubation is required for maximal sterol biosynthesis. A complex mixture of hydrocarbons accompanies squalene in the incubated extracts.
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism*; D002247:Carbon Isotopes; D002474:Cell-Free System; D002776:Cholestanes / Q000378:metabolism; D002784:Cholesterol / Q000096:biosynthesis*; D002852:Chromatography, Ion Exchange; D002855:Chromatography, Thin Layer; D004952:Esters / Q000378:metabolism; D005260:Female; D005978:Glutathione / Q000494:pharmacology; D006600:Hexosephosphates / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D008798:Mevalonic Acid / Q000378:metabolism; D009243:NAD / Q000494:pharmacology; D009536:Niacinamide / Q000494:pharmacology; D051381:Rats; D013185:Squalene / Q000378:metabolism*; D013261:Sterols / Q000096:biosynthesis; D013997:Time Factors
D002247:Carbon Isotopes; D002776:Cholestanes; D004952:Esters; D006600:Hexosephosphates; D013261:Sterols; D009243:NAD; D009536:Niacinamide; D013185:Squalene; D000255:Adenosine Triphosphate; D002784:Cholesterol; D005978:Glutathione; D008274:Magnesium; D008798:Mevalonic Acid