Induction of cysteine dioxygenase activity by oral administration of cysteine analogues to the rat: implications for drug efficacy and safety.
One of the major steps in the oxidation of the sulphur-containing amino acid, L-cysteine, is the production of cysteine sulphinic acid, catalysed by the enzyme cysteine dioxygenase. This enzyme plays a key role in the intermediary metabolism of sulphur-containing compounds. The activity of this crucial enzyme is known to be influenced by sulphur-compound intake, being increased in animals fed an excess of L-cysteine or methionine. However, the affects on this enzyme of the chronic administration of drugs similar in structure to cysteine are unknown. This has now been investigated using the anti-rheumatic agent, D-penicillamine, and the mucoactive compound, S-carboxymethyl-L-cysteine. Repeated oral administration of these sulphur-containing drugs to male Wistar rats for five consecutive days led to a significant increase in hepatic cysteine dioxygenase activity. This increase in the production rate of cysteine sulphinic acid remained evident until returning to control levels four days after cessation of drug administration. These observations provide evidence that these two drugs interact with the intermediary biochemistry of sulphur compounds and may provide hitherto unappreciated insights into mechanisms by which therapeutic effects and adverse reactions may occur.
Roopnarinesingh
E S
ES
Section of Biological Chemistry, Division of Biomedical Sciences, Faculty of Medicine, Imperial College London, South Kensington, UK.
Steventon
G B
GB
Harris
R M
RM
Waring
R H
RH
Mitchell
S C
SC
D000284:Administration, Oral; D000818:Animals; D000891:Anti-Infective Agents, Local / Q000494:pharmacology*; D018501:Antirheumatic Agents / Q000494:pharmacology*; D002233:Carbocysteine / Q000494:pharmacology*; D003545:Cysteine / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000378:metabolism; D050558:Cysteine Dioxygenase / Q000032:analysis / Q000378:metabolism*; D003547:Cysteine Synthase / Q000378:metabolism; D003600:Cytosol / Q000201:enzymology; D004334:Drug Administration Schedule; D004789:Enzyme Activation; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D010084:Oxidation-Reduction; D010396:Penicillamine / Q000494:pharmacology*; D051381:Rats; D013455:Sulfur / Q000378:metabolism
D000891:Anti-Infective Agents, Local; D018501:Antirheumatic Agents; D013455:Sulfur; D002233:Carbocysteine; D050558:Cysteine Dioxygenase; D003547:Cysteine Synthase; D010396:Penicillamine; D003545:Cysteine; C013461:cysteine sulfinic acid