Myeloperoxidase catalysed cooxidative metabolism of methimazole: oxidation of glutathione and NADH by free radical intermediates.
Chem Biol Interact
; 73(2-3): 279-95, 1990.
Article
en En
| MEDLINE
| ID: mdl-2155713
The myeloperoxidase catalysed oxidation of methimazole in the presence of NADH or GSH resulted in oxygen uptake suggesting that metabolism proceeded via a one electron mechanism. The GSH was oxidised to GSSG and the thiyl radical could be trapped with DMPO while NADH was oxidized to NAD+. Metabolism proceeded without the inactivation of the enzyme myeloperoxidase. Myeloperoxidase catalyzed oxidation of other substrates which proceed via one electron intermediates; 2,6-dimethylphenol, N,N,N',N'-tetramethyl-phenylenediamine and luminol, were all stimulated by methimazole providing further evidence for a methimazole free radical. The presence of iodide stimulated the oxidation of methimazole but inhibited the oxygen uptake in the presence of GSH or NADH suggesting that metabolism in this case proceeded by a two electron mechanism. In contrast, another S-thioureylene drug, thiourea; did not cause oxygen uptake when oxidised in the presence of GSH or NADH indicating that the myeloperoxidase oxidation of thiourea proceeded primarily by a two electron mechanism. The horseradish peroxidase catalysed one electron oxidation of p'p'-biphenol, and 3,3',5,5'-tetramethylbenzidine was reversibly inhibited by methimazole and thiourea by preventing the accumulation of oxidation products via reductive mechanisms whereas the reversible inhibition of guaiacol and luminol oxidation was the result of competitive inhibition. With p,p'-biphenol, and 3,3',5,5'-tetramethylbenzidine unstable adduct formation could be demonstrated.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Peroxidasa
/
Glutatión
/
Metimazol
/
NAD
Idioma:
En
Revista:
Chem Biol Interact
Año:
1990
Tipo del documento:
Article
País de afiliación:
Canadá
Pais de publicación:
Irlanda