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The stereospecific suicide inhibition of human melanoma thioredoxin reductase by 13-cis-retinoic acid

1989; Elsevier BV; Volume: 160; Issue: 2 Linguagem: Inglês

10.1016/0006-291x(89)92471-6

1090-2104

Karin U. Schallreuter, J.M. Wood,

Glutathione Transferases and Polymorphisms

13-cis retinoic acid has been shown to be a stereospecific suicide inhibitor of thioredoxin reductase purified from human melanoma tissue. All trans retinoic acid does not inhibit this enzyme. The covalent addition of 13-cis retinoic acid to the thiolate active site of thioredoxin reductase produces a thioether enzyme-inhibitor complex. This has been established by a kinetic analysis and by active site labeling with 3H-13 cis retinoic acid. A mechanism involving Michael addition of the thiolate group in the active site of thioredoxin reductase to the 13-cis double bond of enzyme-bound inhibitor has been proposed. This reaction may be important in the human epidermis because thioredoxin reductase has been shown to be a major antioxidant catalyst in human keratinocytes, melanocytes, melanoma cells, and in human skin as well as in melanoma tissues.