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Monitoring the Reductive and Oxidative Half-Reactions of a Flavin-Dependent Monooxygenase using Stopped-Flow Spectrophotometry
Published on: March 18, 2012
Phenylalanine 4-monooxygenase: the "sulfoxidation polymorphism"
Stephen C Mitchell1, Glyn B Steventon2
1Section of Computational and Systems Medicine, Faculty of Medicine, Imperial College London, London, UK.
Summary
Genetic variations affect how individuals process S-carboxymethyl-l-cysteine, impacting sulfoxidation. Poor sulfoxidation is linked to diseases, particularly neurodegenerative disorders, suggesting broader enzyme functions.
Area of Science:
- Biochemistry
- Pharmacogenetics
- Enzymology
Background:
- Inter-individual differences in S-carboxymethyl-l-cysteine S-oxidation have been observed for decades.
- Genetic and environmental factors influence this sulfoxidation ability, which is independent of age and gender.
- Poor sulfoxidation is more prevalent in patients with various diseases, especially neurodegenerative disorders.
Purpose of the Study:
- To identify the enzyme responsible for S-carboxymethyl-l-cysteine S-oxygenation.
- To explore the potential broader roles of metabolic enzymes in protecting against toxic assault.
Main Methods:
- Analysis of S-carboxymethyl-l-cysteine excretion patterns in urine.
- Comparative studies between healthy volunteers and patient cohorts.
- Enzyme identification through biochemical investigation.
Main Results:
- The enzyme responsible for S-oxygenation was identified as phenylalanine 4-monooxygenase (a tetrahydrobiopterin-dependent aromatic amino acid hydroxylase).
- A higher prevalence of poor sulfoxidizers was observed in patient groups, particularly those with neurodegenerative diseases.
Conclusions:
- Phenylalanine 4-monooxygenase plays a role in S-carboxymethyl-l-cysteine metabolism beyond phenylalanine hydroxylation.
- Metabolic enzymes may possess unrecognised protective functions against xenobiotics or endogenous toxins.
Keywords:
Phenylalanine 4-monooxygenaseS-carboxymethyl-l-cysteinephenotypephenylalaninephenylalanine hydroxylasesulfoxidationMore Related Videos
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