The Formation and Reduction of the 14,15-double Bond in Cholesterol Biosynthesis

Overview

Journal Biochem J

Specialty Biochemistry

Date 1971 Jan 1

PMID 4398958

Citations 10

Authors

I A Watkinson

D C Wilton

K A MUNDAY

M Akhtar

Affiliations

Soon will be listed here.

Abstract

It was shown that 100mug quantities of 4,4'-dimethyl[2-(3)H(2)]cholesta-8,14-dien-3beta-ol (IIIa), tritiated cholesta-8,14-dien-3beta-ol, 4,4'-dimethyl[2-(3)H(2)]cholesta-7,14-dien-3beta-ol, dihydro[2-(3)H(2)]lanosterol and [24-(3)H]lanosterol were converted by a 10000g supernatant of rat liver homogenate into cholesterol in 17%, 54%, 6%, 9.5% and 24% yields respectively. From an incubation of dihydro[3alpha-(3)H]lanosterol with a rat liver homogenate in the presence of a trap up to 38% of the radioactivity was found to be associated with a fraction that was unambiguously shown to be 4,4'-dimethylcholesta-8,14-dien-3beta-ol. Another related compound, 4,4'-dimethylcholesta-7,14-dien-3beta-ol was also shown to be equally effective in its ability to trap compound (IIIa) from an incubation of dihydro[3alpha-(3)H]lanosterol. The mechanism of the further conversion of the compound (IIIa) into cholesterol occurred by the reduction of the 14,15-double bond and involved the addition of a hydrogen atom from the medium to C-15 and another from the 4-position of NADPH to C-14. Two possible mechanisms for the removal of the 14alpha-methyl group in sterol biosynthesis are discussed.

Citing Articles

The biosynthesis of cholesta-8,14-dien-3beta-ol by Chang human liver cells.

Wilton D Biochem J. 1971; 125(4):1153-4.

PMID: 5144235 PMC: 1178282. DOI: 10.1042/bj1251153.

The effect of carbon monoxide on the nature of the accumulated 4,4-dimethyl sterol precursors of cholesterol during its biosynthesis from (2-14C)mevalonic acid in vitro.

Gibbons G, Mitropoulos K Biochem J. 1973; 132(3):439-48.

PMID: 4724584 PMC: 1177607. DOI: 10.1042/bj1320439.

The metabolic sequence by which some 4,4-dimethyl sterols are converted into cholesterol.

Gibbons G Biochem J. 1974; 144(1):59-68.

PMID: 4462576 PMC: 1168464. DOI: 10.1042/bj1440059.

A novel olefinic rearrangement. The enzymic conversion of cholesta-7,9-dien-3 -ol into cholesta-8,14-dien-3 -ol.

Akhtar M, Freeman C, Rahimtula A, Wilton D Biochem J. 1972; 129(2):225-9.

PMID: 4404936 PMC: 1174072. DOI: 10.1042/bj1290225.

Studies on the mechanism and regulation of C-4 demethylation in cholesterol biosynthesis. The role of adenosine 3':5'-cyclic monophosphate.

Bloxham D, Wilton D, Akhtar M Biochem J. 1971; 125(2):625-34.

PMID: 4401381 PMC: 1178100. DOI: 10.1042/bj1250625.

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