A review of xenobiotic metabolism enzymes in Parkinson's disease and motor neuron disease.
The role of xenobiotic metabolising enzymes (XMEs) in disease aetiology has been under investigation by numerous researchers around the world for the last two decades. The association of a number of defects in both phase I and phase II reactions with Parkinson's disease (PD) and motor neuron disease (MND) have been extensively studied. This review of the work of the group based initially at the University of Birmingham into the functional genomics of XMEs and neurodegenerative diseases has indicated that: 1. Sub-groups of patients with PD and MND can be identified with problems in xenobiotic metabolism by in vivo or in vitro methods. 2. 38-39% of the patients with MND/PD have a defect in the S-oxidation of the mucoactive drug, carbocysteine, by an unknown cytosolic oxidase(s). The odds risk ratio for the association of this defect with these diseases was calculated to be 10.21 for MND and 10.50 for PD. 3. Patients with PD appear to have an altered substrate specificity for monoamine oxidase B substrates in an in vitro platelet assay. 4. Patients with MND have an increased capacity to S-methylate aliphatic sulphydryl compounds in an in vivo challenge as well as an in vitro erythrocyte thiol methyltransferase assay. The results of over a decade of investigations into both PD and MND indicate that these are diseases with mutifactorial origins that encompass both genetic predisposition and environmental insult.
Steventon
G B
GB
Department of Pharmacy, School of Health and Life Sciences, King's College London, UK. glyn.steventon@kcl.ac.uk
Sturman
S
S
Waring
R H
RH
Williams
A C
AC
D000328:Adult; D000368:Aged; D002233:Carbocysteine / Q000378:metabolism; D016022:Case-Control Studies; D005100:Expectorants / Q000378:metabolism; D006801:Humans; D008745:Methylation; D008780:Methyltransferases / Q000378:metabolism; D008875:Middle Aged; D008995:Monoamine Oxidase / Q000378:metabolism; D016472:Motor Neuron Disease / Q000201:enzymology* / Q000235:genetics; D016017:Odds Ratio; D010084:Oxidation-Reduction; D010300:Parkinson Disease / Q000201:enzymology* / Q000235:genetics; D010641:Phenotype; D018709:Statistics, Nonparametric; D013379:Substrate Specificity; D015262:Xenobiotics / Q000378:metabolism*
D005100:Expectorants; D015262:Xenobiotics; D002233:Carbocysteine; D008995:Monoamine Oxidase; D008780:Methyltransferases; C022742:thiol S-methyltransferase