Imperial College London
Alternate

DrSteveMitchell

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Visiting Reader
 
 
 
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Contact

 

+44 (0)20 7594 3180s.c.mitchell

 
 
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Location

 

Office no. 362Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Rawlings:2019:10.1515/dmpt-2018-0038,
author = {Rawlings, L and Turton, L and Mitchell, SC and Steventon, GB},
doi = {10.1515/dmpt-2018-0038},
journal = {Drug Metab Pers Ther},
title = {Drug S-oxidation and phenylalanine hydroxylase: a biomarker for neurodegenerative susceptibility in Parkinson's disease and amyotrophic lateral sclerosis.},
url = {http://dx.doi.org/10.1515/dmpt-2018-0038},
volume = {34},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Background The S-oxidation of S-carboxymethyl-L-cysteine has been reported previously to be a biomarker of disease susceptibility in Parkinson's disease and amyotrophic lateral sclerosis. In the present investigation, the original observations have been extended and confirmed. Methods Meta-analysis of previously published investigations into the S-oxidation polymorphism together with new subject data was evaluated. Results The incidence of the poor metaboliser phenotype (no urinary recovery of S-oxide metabolites) was found to be 3%-7% within healthy and non-neurological disease populations, whereas 38% of the Parkinson's disease subjects and 39% of the amyotrophic lateral sclerosis group were phenotyped as poor metabolisers. The consequent odds risk ratio of developing Parkinson's disease was calculated to be 33.8 [95% confidence interval (CI), 13.3-86.1] and for amyotrophic lateral sclerosis was 35.2 (95% CI, 13.0-85.1). Conclusions The possible involvement of the enzyme responsible for this S-oxidation biotransformation reaction, phenylalanine hydroxylase, should be further investigated to elucidate its potential role in the mechanism(s) of toxicity in susceptible individuals displaying these diseases. The "Janus hypothesis," possibly explaining why phenylalanine hydroxylase is a biomarker of neurodegenerative disease susceptibility, together with the general theme that this concept may apply to many other hitherto unsuspected enzyme systems, is presented.
AU  - Rawlings,L
AU  - Turton,L
AU  - Mitchell,SC
AU  - Steventon,GB
DO  - 10.1515/dmpt-2018-0038
PY  - 2019///
TI  - Drug S-oxidation and phenylalanine hydroxylase: a biomarker for neurodegenerative susceptibility in Parkinson's disease and amyotrophic lateral sclerosis.
T2  - Drug Metab Pers Ther
UR  - http://dx.doi.org/10.1515/dmpt-2018-0038
UR  - https://www.ncbi.nlm.nih.gov/pubmed/30939113
VL  - 34
ER  -
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