Carbon-carbon bond cleavage and formation reactions in drug metabolism and the role of metabolic enzymes

Elimination of xenobiotics from the human body is often facilitated by a transformation to highly water soluble and more ionizable molecules. In general, oxidation-reduction, hydrolysis, and conjugation reactions are common biotransformation reactions that are catalyzed by various metabolic enzymes...

Full description

Saved in:
Bibliographic Details
Published in:Drug metabolism reviews 2015-10, Vol.47 (4), p.534-557
Main Authors: Bolleddula, Jayaprakasam, Chowdhury, Swapan K.
Format: Article
Language:English
Subjects:
Animals
Carbon - metabolism
Carbon-carbon bond cleavage
carbon-carbon bond formation
Cytochrome P-450 Enzyme System - metabolism
drug metabolism
Humans
Inactivation, Metabolic
mechanisms
metabolic enzymes
Oxidation-Reduction
rare biotransformations
Xenobiotics - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Elimination of xenobiotics from the human body is often facilitated by a transformation to highly water soluble and more ionizable molecules. In general, oxidation-reduction, hydrolysis, and conjugation reactions are common biotransformation reactions that are catalyzed by various metabolic enzymes including cytochrome P450s (CYPs), non-CYPs, and conjugative enzymes. Although carbon-carbon (C-C) bond formation and cleavage reactions are known to exist in plant secondary metabolism, these reactions are relatively rare in mammalian metabolism and are considered exceptions. However, various reactions such as demethylation, dealkylation, dearylation, reduction of alkyl chain, ring expansion, ring contraction, oxidative elimination of a nitrile through C-C bond cleavage, and dimerization, and glucuronidation through C-C bond formation have been reported for drug molecules. Carbon-carbon bond cleavage reactions for drug molecules are primarily catalyzed by CYP enzymes, dimerization is mediated by peroxidases, and C-glucuronidation is catalyzed by UGT1A9. This review provides an overview of C-C bond cleavage and formation reactions in drug metabolism and the metabolic enzymes associated with these reactions.
ISSN:0360-2532
1097-9883
DOI:10.3109/03602532.2015.1086781