Abstract
Phenylalanine 4-monooxygenase is a hepatic enzyme that controls the rate of catabolism of Lphenylalanine in man. Genetic defects in the phenylalanine 4-monooxygenase gene are known to be the cause of the majority of cases of phenylketonuria and these defects are now well characterized at the DNA and proteomic levels. However, the role of the phenylalanine 4-monooxygenase in xenobiotic metabolism is poorly understood. This Fe containing non-haem cytosolic monoxygenase is responsible for the S-oxidation of the thioether moiety of the mucoactive drugs, S-carboxymethyl-L-cysteine and S-methyl-L-cysteine, the major route of metabolism of these compounds. This S-oxidation biotransformation is regulated at both the genetic and hormonal level and results in both qualitative and quantitative differences in the metabolic profiles seen in individuals. To date the molecular genetic defects associated with the S-oxidation polymorphism are unknown and remain to be identified. Phenylalanine 4-monooxygenase appears to be like xanthine oxidase, aldehyde oxidase, prostaglandin H synthase, lipooxygenase and dopamine β-hydroxylase. Enzymes of intermediary metabolism are certainly involved in drug metabolism and their role will become more important and widespread in the future.
Keywords: Phenylalanine 4-monooxygenase, S-carboxymethyl-L-cysteine, S-oxidation, genetic polymorphism, hormonal regulation
Letters in Drug Design & Discovery
Title: Non-Classical Drug Metabolism Enzymes: The Curious Case of Phenylalanine 4-Monooxygenase
Volume: 3 Issue: 6
Author(s): G. B. Steventon and S. C. Mitchell
Affiliation:
Keywords: Phenylalanine 4-monooxygenase, S-carboxymethyl-L-cysteine, S-oxidation, genetic polymorphism, hormonal regulation
Abstract: Phenylalanine 4-monooxygenase is a hepatic enzyme that controls the rate of catabolism of Lphenylalanine in man. Genetic defects in the phenylalanine 4-monooxygenase gene are known to be the cause of the majority of cases of phenylketonuria and these defects are now well characterized at the DNA and proteomic levels. However, the role of the phenylalanine 4-monooxygenase in xenobiotic metabolism is poorly understood. This Fe containing non-haem cytosolic monoxygenase is responsible for the S-oxidation of the thioether moiety of the mucoactive drugs, S-carboxymethyl-L-cysteine and S-methyl-L-cysteine, the major route of metabolism of these compounds. This S-oxidation biotransformation is regulated at both the genetic and hormonal level and results in both qualitative and quantitative differences in the metabolic profiles seen in individuals. To date the molecular genetic defects associated with the S-oxidation polymorphism are unknown and remain to be identified. Phenylalanine 4-monooxygenase appears to be like xanthine oxidase, aldehyde oxidase, prostaglandin H synthase, lipooxygenase and dopamine β-hydroxylase. Enzymes of intermediary metabolism are certainly involved in drug metabolism and their role will become more important and widespread in the future.
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Cite this article as:
Steventon B. G. and Mitchell C. S., Non-Classical Drug Metabolism Enzymes: The Curious Case of Phenylalanine 4-Monooxygenase, Letters in Drug Design & Discovery 2006; 3 (6) . https://dx.doi.org/10.2174/157018006777805512
DOI https://dx.doi.org/10.2174/157018006777805512 |
Print ISSN 1570-1808 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-628X |
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