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Cited by 199Metal-Catalyzed Oxygenation MechanismsOxidative Organic Chemistry ReactionsPhysical Organic Chemistry and Reaction Kinetics

The DOI matches its Crossref record; 45 of the 50 references it cites were found in a registry or an index.

Mechanistic studies on aromatase and related CC bond cleaving P-450 enzymes

Akhtar, Muhammad, Njar, Vincent C.O., Neville Wright, J.·1993·The Journal of Steroid Biochemistry and Molecular Biology
DOI 10.1016/0960-0760(93)90241-n
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Abstract

Some P-450 systems, notably aromatase and 14 alpha-demethylase catalyse not only the hydroxylate reaction but also the oxidation of an alcohol into a carbonyl compound as well as a C-C bond cleavage process. All these reactions occur at the same active site. A somewhat analogous situation is noted with 17 alpha-hydroxylase-17,20-lyase that participates in hydroxylation as well as C-C bond cleavage process. The C-C bond cleavage reactions catalysed by the above enzymes conform to the general equation: [formula: see text] It is argued that all three types of reaction catalyzed by these enzymes may be viewed as variations on a common theme. In P-450 dependent hydroxylation the initially formed FeIII-O-O. species is converted into FeIII-O-OH and the heterolysis of the oxygen-oxygen bond of the latter then gives the oxo-derivative for which a number of canonical structures are possible; for example FeV = O<==>(+.)FeIV = O<==>FeIV-O.. One of these, FeIV-O. behaves like an alkoxyl radical and participates in hydrogen abstraction from C-H bond to produce FeIV-OH and carbon radical. The latter is then quenched by the delivery of hydroxyl radical from FeIV-OH. The latter species may thus be regarded as a carrier of hydroxyl radical. We have proposed that the C-C bond cleavage reaction occurs through the participation of the FeIII-O-OH species that is trapped by the electrophilic property of the carbonyl compound giving a peroxide adduct that fragments to produce an acyl-carbon cleavage. Scientific developments leading up to this conclusion are considered. In the first author's views, "The study of mechanisms is not a scientific but a cultural activity. Mechanisms do not aim at an absolute truth but are intended to be a "running" commentary on the status of knowledge in a field. As the structural knowledge in a field advances Mechanisms evolve to take note of the new findings. Just as a constructive "running" commentary provides the stimulus for higher standards of performance, so Mechanisms call for better and firmer structural information from their practitioners".

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Crossref · 10.1016/0960-0760(93)90241-n

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Research works printed but not linked: 1

  1. Treaskos, 1986, Microsomal enzymes of cholesterol biosynthesis, J. Biol. Chem., 261, 14651

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Metadata

Authors
Akhtar, M., Njar, V. C. O., & Neville Wright, J.
Affiliations
University of Southampton (GB)
Corresponding author
Akhtar, Muhammad
ORCID
Venue
The Journal of Steroid Biochemistry and Molecular Biology
Publisher
Elsevier BV
Published
1993-03
Volume
44
Issue
4-6
Pages
375-387
ISSN
0960-0760 (ISSN-L)
DOI
10.1016/0960-0760(93)90241-n
OpenAlex
W2015325021
Cited by
193
References
50
Citations by year
2024: 2 · 2023: 3 · 2022: 6 · 2021: 3 · 2020: 6 · 2019: 3 · 2018: 3 · 2017: 31 · 2016: 4 · 2015: 29 · 2014: 4 · 2013: 2 · 2012: 3
FWCI
5.29
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • The Journal of Steroid Biochemistry and Molecular Biology (publishedVersion)
  • PubMed (publishedVersion)
  • Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
Funders
Wellcome Trust
Topics
  • Physical Sciences › Chemistry › Inorganic Chemistry › Metal-Catalyzed Oxygenation Mechanisms
  • Physical Sciences › Chemistry › Organic Chemistry › Oxidative Organic Chemistry Reactions
  • Physical Sciences › Chemistry › Organic Chemistry › Physical Organic Chemistry and Reaction Kinetics
Keywords
aromatase, cytochrome P450, C–C bond cleavage, reaction mechanism, hydroxyl radicals, heterolysis, steroid hydroxylation, alcohol oxidation
MeSH terms
Animals, Aromatase, Cytochrome P-450 Enzyme System, Female, Humans, Hydroxylation, Male, Models, Theoretical, Oxidation-Reduction, Substrate Specificity, Molecular Structure

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