Schallreuter K U, Wood J M
Department of Dermatology, University of Hamburg, FRG.
Biochem Biophys Res Commun. 1989 Apr 28;160(2):573-9. doi: 10.1016/0006-291x(89)92471-6.
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.
13-顺式视黄酸已被证明是从人黑色素瘤组织中纯化出的硫氧还蛋白还原酶的立体特异性自杀抑制剂。全反式视黄酸不抑制这种酶。13-顺式视黄酸与硫氧还蛋白还原酶的硫醇盐活性位点共价加成产生硫醚酶-抑制剂复合物。这已通过动力学分析和用3H-13顺式视黄酸进行活性位点标记得以证实。有人提出了一种机制，即硫氧还蛋白还原酶活性位点中的硫醇盐基团对酶结合抑制剂的13-顺式双键进行迈克尔加成。该反应在人类表皮中可能很重要，因为硫氧还蛋白还原酶已被证明是人类角质形成细胞、黑素细胞、黑色素瘤细胞以及人类皮肤和黑色素瘤组织中的主要抗氧化催化剂。
