Lack of congruence between cysteine dioxygenase activity and S-carboxymethyl-L-cysteine S-oxidation activity in rat cytosol.
The identity of the enzyme(s) responsible for the S-oxidation of the mucoactive drug S-carboxymethyl-L-cysteine (SCMC) is unknown but the protein(s) are a susceptibility factor for a number of chronic degenerative diseases. The structural similarities between the amino acid L-cysteine and SCMC have raised the possibility that cysteine dioxygenase (CDO) may be responsible for this biotransformation reaction. Both CDO and SCMC S-oxygenase were found to require Fe2+ for enzymatic activity, and both enzyme activities were inhibited by Fe2+ and Fe3+ chelators. However, sulphydryl group modification of the enzymes resulted in the activation of the S-oxidation of SCMC but inhibition of the S-oxidation of L-cysteine. When the two enzyme activities were quantified in 20 female hepatic cytosolic fractions no linear correlation in the production of their respective metabolites was seen. The results of this investigation indicate that CDO is not responsible for the S-oxidation of SCMC in the rat.
Department of Pharmacy, School of Health and Life Sciences, King's College London, Franklin-Wilkins Building, 150 Stamford Street, SE1 9NN, UK.
Samera
S
Khan
Stephen C
SC
Mitchell
Glyn B
GB
Steventon
D000818:Animals; D001711:Biotransformation / Q000187:drug effects; D002233:Carbocysteine / Q000378:metabolism*; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D003545:Cysteine / Q000494:pharmacology; D050558:Cysteine Dioxygenase; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D049308:Dioxygenases / Q000378:metabolism* / Q000494:pharmacology; D004347:Drug Interactions; D005260:Female; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D010084:Oxidation-Reduction / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D002614:Chelating Agents; D002233:Carbocysteine; D049308:Dioxygenases; D050558:Cysteine Dioxygenase; D003545:Cysteine