1971LipidsRequires access

The biosynthesis of cholesterol and other sterols by brain tissue: I. Subcellular biosynthesis in vitro

Robert B. Ramsey, John‐Paul Jones, S. H. M. Naqvi, Harold J. Nicholas

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Abstract

Abstract The biosynthesis of cholesterol by subcellular particles from rat brain was studied with several labeled cholesterol precursors as substrates. Rats from two age groups were used for preparation of the subcellular fractions: 15‐day‐old and adult. Microsomes and a soluble fraction were required for maximum biosynthesis of14C‐nonsaponifiable material. The latter was synthesized in good yield by subcellular fractions from both age groups, but 90% or more was present as14C‐squalene, when either U‐14C‐glucose, 2‐14C‐sodium acetate or 2‐14C‐mevalonic acid was the radioactive substrate. Neither3H‐squalene oxide nor14C‐lanosterol was converted to sterol when incubated with microsomal+soluble preparations, but some 4% of14C‐desmosterol was converted to cholesterol by adult preparations. Thus a metabolic block, largely between squalene to desmosterol, exists in isolated microsomal+soluble preparations from both 15‐day‐old and adult rat brain.

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Abstract The biosynthesis of cholesterol by subcellular particles from rat brain was studied with several labeled cholesterol precursors as substrates. Rats from two age groups were used for preparation of the subcellular fractions: 15‐day‐old and adult. Microsomes and a soluble fraction were required for maximum biosynthesis of14C‐nonsaponifiable material. The latter was synthesized in good yield by subcellular fractions from both age groups, but 90% or more was present as14C‐squalene, when either U‐14C‐glucose, 2‐14C‐sodium acetate or 2‐14C‐mevalonic acid was the radioactive substrate. Neither3H‐squalene oxide nor14C‐lanosterol was converted to sterol when incubated with microsomal+soluble preparations, but some 4% of14C‐desmosterol was converted to cholesterol by adult preparations. Thus a metabolic block, largely between squalene to desmosterol, exists in isolated microsomal+soluble preparations from both 15‐day‐old and adult rat brain.

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Available abstract

Abstract The biosynthesis of cholesterol by subcellular particles from rat brain was studied with several labeled cholesterol precursors as substrates. Rats from two age groups were used for preparation of the subcellular fractions: 15‐day‐old and adult. Microsomes and a soluble fraction were required for maximum biosynthesis of14C‐nonsaponifiable material. The latter was synthesized in good yield by subcellular fractions from both age groups, but 90% or more was present as14C‐squalene, when either U‐14C‐glucose, 2‐14C‐sodium acetate or 2‐14C‐mevalonic acid was the radioactive substrate. Neither3H‐squalene oxide nor14C‐lanosterol was converted to sterol when incubated with microsomal+soluble preparations, but some 4% of14C‐desmosterol was converted to cholesterol by adult preparations. Thus a metabolic block, largely between squalene to desmosterol, exists in isolated microsomal+soluble preparations from both 15‐day‐old and adult rat brain.

Key concepts: Desmosterol, Squalene, Lanosterol, Biosynthesis, Microsome, Biochemistry, Mevalonic acid, Cholesterol

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