Popis: |
A detailed study was made of methyl sterols involved in cholesterol biosynthesis in adult brain following intracerebral injection of [2-14C]mevalonic acid and incubation of this cholesterol precursor with adult brain cell-free preparations. High specific activity lanosterol, 4,4-dimethyl-5α-cholesta-8(9)-24-dien-3β-ol, 4α-methyl-5α-cholesta-7, 24-dien-3β-ol, and 5α-cholesta-7, 24-dien-3β-ol were formed 1 hour after intracerebral injection of the 14C-labeled precursor. Labeled to a lesser extent were 4,4, 14α-trimethyl-5α-cholest-7-en-3β-ol, 4α-methyl-5α-cholest-7-en-3β-ol, desmosterol, and cholesterol. Detected by mass only was 4α, 14α-dimethyl-5α-cholest-7-en-3β-ol. Incubation of adult rat brain cell-free preparations with [2-14C]mevalonic 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-5α-cholesta-14(15), 24-dien-3β-ol and 4α-methyl-5α-cholesta-14(15), 24-dien-3β-ol. 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. |