Biosynthesis of squalene and cholesterol by cell-free extracts of adult rat brain

• Main Authors: M.T. Kelley, R.T. Aexel, B.L. Herndon, H.J. Nicholas
• Format: Article
• Language: English
• Published: Elsevier 1969-03-01
• Series: Journal of Lipid Research
• Subjects: cholesterol companions; biosynthetic hydrocarbons; brain esters; nicotinamide
• Online Access: http://www.sciencedirect.com/science/article/pii/S002222752042663X

Cell-free extracts of adult rat brain incubated with mevalonic acid-2-14C synthesize 14C-labeled nonsaponifiable fractions consisting largely of squalene-14C. 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 14C-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-14C, 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.