Journal of Lipid Research, Vol. 10, 166-174, March 1969
Copyright © 1969 by Lipid Research, Inc.

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

M. T. Kelley , R. T. Aexel , B. L. Herndon , and H. J. Nicholas

Institute of Medical Education and Research and the Department of Biochemistry, St. Louis University School of Medicine, St. Louis, Missouri 63104

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.

Supplementary key words cholesterol companions • biosynthetic hydrocarbons • brain esters • nicotinamide

Submitted on June 5, 1968
Accepted on October 8, 1968

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