SULFOXIDATION AND SULFATION CAPACITY IN PATIENTS WITH PRIMARY BILIARY-CIRRHOSIS

We have previously reported an association of impaired S-oxidation wit h primary biliary cirrhosis, In order to confirm and further define th is relationship, we retested S-oxidation capacity via three metabolic pathways and sulphation capacity via a fourth pathway. Metabolism of S -carboxymethyl-L-cysteine is polymorphic -20% of healthy individuals b eing poor S-oxidisers, We found 26% with primary biliary cirrhosis wer e poor S-oxidisers, compared with 36% with other liver disease and 25% of healthy controls, Differences were not statistically significant. S-oxidation of ranitidine is dependent upon flavin mono-oxygenases, We showed a non-significant trend toward less S-oxide in primary biliary cirrhosis and other liver disease, compared with healthy controls, wi th no significant difference between disease groups, Conversion of cys teine to sulphate depends predominantly on cysteine dioxygenase, Impai red activity may be reflected by decreased plasma sulphate and elevate d cysteine, We found that the plasma cysteine:sulphate ratio was signi ficantly elevated not only in primary biliary cirrhosis (p<0.0001), bu t also in other liver disease (p<0.0001), compared with healthy indivi duals. Sulphation capacity was studied by analysing paracetamol metabo lism, Paracetamol sulphate and sulphate: glucuronide ratio were reduce d in primary biliary cirrhosis compared with normal individuals, (p<0. 05), A trend towards less sulphate in primary biliary cirrhosis compar ed other liver disease was not significant (p = 0.42). We conclude tha t although sulphation and some sulphoxidation pathways are impaired in primary biliary cirrhosis, we can currently find no evidence to subst antiate the hypothesis that primary biliary cirrhosis is a disease spe cifically associated with poor S-oxidation, as assessed via these meta bolic pathways.