Formation of Methyl Sterols in Brain Cholesterol Biosynthesis STEROL FORMATIOD: IAl- VITRO ASD IX VIVO IN ADULT RAT BRAIX* (Received for publication, May 6, 19il)
نویسنده
چکیده
A detailed study was made of methyl sterols involved in cholesterol biosynthesis in adult brain following intracerebral injection of [ZJ4C]mevalonic acid and incubation of this cholesterol precursor with adult brain cell-free preparations. High specific activity lanosterol, 4,4-dimethyl-&-cholestaS(9)-24-dien-3P-01, 4a-methyl-5a-cholesta-‘7,24-dien-3/3-o1, and Sa-cholesta-7,24-dien-3/?-ol were formed 1 hour after intracerebral injection of the 14C-labeled precursor. Labeled to a lesser extent were 4,4,14oc-trimethyl-Sa-cholest7-en-3P-01, 4ar-methyl-Scr-cholest-7-en-j/3-01, desmosterol, and cholesterol. Detected by mass only was 4ar,14c~dimethyl-Sor-cholest-7-en-30-01. Incubation of adult rat brain cell-free preparations with [2J4C$nevalonic acid yielded two highly labeled methyl sterols. Based on gas chromatographic retention data and gas chromatography-mass spectrometry, these methyl sterols have tentatively been identified as 4,4-dimethyl-5a-cholesta-14(15),24-dien-3&ol and 4oL-methyl-Sar-cholesta-14( 15)) 24 dien 30 01. The results indicate that the primary pathway of sterol biosynthesis in adult brain is through diunsaturated sterols. The sterols formed in vitro suggest a partial disruption or alteration of the biosynthetic pathway as a result of maceration of the tissue.
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