PHENOTYPIC VARIATION IN XENOBIOTIC METABOLISM AND ADVERSE ENVIRONMENTAL RESPONSE - FOCUS ON SULFUR-DEPENDENT DETOXIFICATION PATHWAYS

Proper bodily response to environmental toxicants presumably requires proper function of the xenobiotic (foreign chemical) detoxification pa thways. Links between phenotypic variations in xenobiotic metabolism a nd adverse environmental response have long been sought. Metabolism of the drug S-carboxymethyl-L-cysteine (SCMC) is polymorphous in the pop ulation, having a bimodal distribution of metabolites, 2.5% of the gen eral population are thought to be nonmetabolizers. The researchers dev eloping this data feel this implies a polymorphism in sulfoxidation of the amino acid cysteine to sulfate. While this interpretation is some what controversial, these metabolic differences reflected may have sig nificant effects. Additionally, a significant number of individuals wi th environmental intolerance or chronic disease have impaired sulfatio n of phenolic xenobiotics. This impairment is demonstrated with the pr obe drug acetaminophen and is presumably due to starvation of the sulf otransferases for sulfate substrate. Reduced metabolism of SCMC has be en found with increased frequency in individuals with several degenera tive neurological and immunological conditions and drug intolerances, including Alzheimer's disease, Parkinson's disease, motor neuron disea se, rheumatoid arthritis, and delayed food sensitivity. Impaired sulfa tion has been found in many of these conditions, and preliminary data suggests that it may be important in multiple chemical sensitivities a nd diet responsive autism. In addition, impaired sulfation may be rele vant to intolerance of phenol, tyramine, and phenylic food constituent s, and it may be a factor in the success of the Feingold diet. These s tudies indicate the need for the development of genetic and functional tests of xenobiotic metabolism as tools for further research in epide miology and risk assessment.