Studies on the 14α‐Demethylation Mechanism in Cholesterol Biosynthesis
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TLDR
Functionalization at position 7 in the metabolism of 3 beta-hydroxy-5 alpha-cholest-7-ene-14 alpha-carbaldehyde suggests the direct involvement of the double bond in the elimination of the 14 alpha-formyl group in the biosynthetic pathway from lanosterol to cholesterol.Abstract:
Identification of radioactive 5 alpha-cholest-8(14)-ene-3 beta,7 alpha-diol in extracts obtained from incubations of 3 beta-hydroxy-5 alpha-[7-3H]cholest-7-ene-14 alpha-carbaldehyde with rat liver microsomes is reported. Levels of this diol in incubations of the 14 alpha-[32-3H]carbaldehyde were measured by multiple selected ion monitoring and were found to be of the same order of those of [3H]formate released from the substrate during the removal of the C-32 atom. The results demonstrate that the diol does not originate from known intermediates of cholesterol biosynthesis, i.e. 5 alpha-cholesta-7,14-dien-3 beta-ol, 5 alpha-cholest-7-en-3 beta-ol and from 5 alpha-cholest-8(14)-en-3 beta-ol. Functionalization at position 7 in the metabolism of 3 beta-hydroxy-5 alpha-cholest-7-ene-14 alpha-carbaldehyde suggests the direct involvement of the double bond in the elimination of the 14 alpha-formyl group in the biosynthetic pathway from lanosterol to cholesterol. 5 alpha-Cholest-8(14)-en-3 beta-ol appears not to be involved in the metabolism of the 14 alpha-carbaldehyde.read more
Citations
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Journal ArticleDOI
Sterol 14α-Demethylase Cytochrome P450 (CYP51), a P450 in all Biological Kingdoms
TL;DR: Experimental support is presented for the notion that specific conserved regions in the P450 sequences represent a CYP51 signature, and two possible roles of CYP 51 in P450 evolution are discussed.
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The anti-aflatoxigenic mechanism of cinnamaldehyde in Aspergillus flavus.
TL;DR: The results indicated that twenty five of thirty genes in aflatoxin cluster showed down-regulation by cinnamaldehyde although the cluster regulators aflR and aflS were slightly up-regulated, which may be due to the up-regulation of the oxidative stress-related genes srrA, msnA and atfB being caused by the significant down- Regulatory factor FluG.
Journal ArticleDOI
Lanosterol 14 alpha-methyl demethylase. Isolation and characterization of the third metabolically generated oxidative demethylation intermediate.
TL;DR: The metabolite is efficiently converted to the demethylated delta 8,14-diene sterol in the absence of molecular oxygen or NADPH, thus supporting its identity as the final oxidized intermediate in the lanosterol 14 alpha-methyl demethylase cascade.
Journal ArticleDOI
Properties and structural requirements for substrate specificity of cytochrome P-450-dependent obtusifoliol 14 alpha-demethylase from maize (Zea mays) seedlings.
TL;DR: The results obtained clearly indicate that three distinct domains of the sterol substrate are governing obtusifoliol demethylation by P-450OBT.14DM, a novel constitutive cytochrome P- 450 with a high degree of substrate and product specificity.
Journal ArticleDOI
The 14α-demethylation of obtusifoliol by a cytochrome P-450 monooxygenase from higher plants microsomes
Alain Rahier,Maryse Taton +1 more
TL;DR: It is concluded that in Zea mays microsomes, obtusifoliol is demethylated at C-14 by a cytochrome P-450 containing monooxygenase system.
References
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Journal Article
Protein Measurement with the Folin Phenol Reagent
TL;DR: Procedures are described for measuring protein in solution or after precipitation with acids or other agents, and for the determination of as little as 0.2 gamma of protein.
Journal ArticleDOI
Mass spectrometric investigations of some unsaturated sterols biosynthetically related to cholesterol.
Giovanni Galli,Sandro Maroni +1 more
TL;DR: The identification of characteristic peaks indicating the position of the double bonds in the side chain or in the nucleus of acetate derivatives is described.
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Chemical and enzymic studies on the characterization of intermediates during the removal of the 14alpha-methyl group in cholesterol biosynthesis. The use of 32-functionalized lanostane derivatives.
TL;DR: A detailed overall pathway for the 14alpha-demethylation in cholesterol biosynthesis is considered, and proposals about the mechanism of individual steps in the pathway are made.