Management of early inflammatory arthritis. Genetic factors predicting persistent disease: the role of defective enzyme systems.
In this chapter, we investigate the use of non-toxic 'probe drugs' to give information about basic biochemical pathways. We have examined the hypothesis that a major factor in RA is defective metabolism of sulphur-containing compounds. At least two pathways have been shown to be abnormal in RA. Generally, patients have reduced capacity to metabolize and detoxify thiol compounds by methylation, and have increased levels of plasma cysteine. They also have a lower capacity for S-oxidation of cysteine and its derivatives, with reduced amounts of plasma sulphate. The raised cysteine resulting from less effective metabolism may lead to reduced clearance of immune complexes and a raised inflammatory response in RA patients. Lower plasma sulphate, however, leads to defective tissue synthesis, and makes adequate repair of damaged joints less feasible. The co-existence of defects in these two interacting endogenous pathways serves to perpetuate the disease process, leading to chronic inflammation and tissue destruction. These enzyme defects have been shown to be predictive of persistent disease.
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D000082:Acetaminophen / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D002233:Carbocysteine / Q000378:metabolism; D003545:Cysteine / Q000378:metabolism; D005544:Forecasting; D006801:Humans; D008658:Inactivation, Metabolic; D008745:Methylation; D008780:Methyltransferases / Q000378:metabolism; D010084:Oxidation-Reduction; D013431:Sulfates / Q000378:metabolism
D013431:Sulfates; D000082:Acetaminophen; D002233:Carbocysteine; D008780:Methyltransferases; C022742:thiol S-methyltransferase; D003545:Cysteine