caa a22 4500 46577346X CHVBK 20180323111935.0 cr unu---uuuuu 170327e19900501xx s 000 0 eng 10.1007/BF00372617 doi (NATIONALLICENCE)springer-10.1007/BF00372617 A possible mechanism of action for azelaic acid in the human epidermis [Elektronische Daten] [K. Schallreuter, J. Wood] Summary: Azelaic acid, and other saturated dicarboxylic acids (C9-C12), are shown to be competitive inhibitors of tyrosinase (K I azelaic acid = 2.73×10−3 M) and of membrane-associated thioredoxin reductase (K I azelaic acid = 1.25×10−5 M). The monomethyl ester of azelaic acid does not inhibit thioredoxin reductase, but it does inhibit tyrosinase, although double the concentration is necessary compared with azelaic acid (K I azelaic acid monomethyl ester = 5.24×10−3 M). Neither azelaic acid nor its monomethyl ester inhibit tyrosinase when catechol is used as a substrate instead of l-tyrosine. Therefore, the weak inhibitory action of azelaic acid on tyrosinase appears to be due to the competition of a single carboxylate group on this inhibitor for the α-carboxylate binding site of the l-tyrosine substrate on the enzyme active site. Based on the inhibitor constant on tyrosinase, at least cytotoxic levels of azelaic acid would be required for the direct inhibition of melanin biosynthesis in melanosomes if this mechanism is responsible for depigmentation in the hyperpigmentation disorders lentigo maligna and melasma. Alternatively only 10−5 M azelaic acid is required to inhibit thioredoxin reductase. This enzyme is shown to regulate tyrosinase through a feedback mechanism involving electron transfer to intra-cellular thioredoxin, followed by a specific interaction between reduced thioredoxin and tyrosinase. Furthermore, the thioredoxin reductase/thioredoxin system is shown to be a principal electron donor for the ribonucleotide reductases which regulates DNA synthesis. Inhibition of thioredoxin reductase by azelaic acid provides a rationale for both its depigmenting property and the reversible inhibition of DNA synthesis observed in cultured epidermal cells and also in some of the bacteria associated with acne vulgaris. Springer-Verlag, 1990 Azelaic acid nationallicence Inhibitor nationallicence Tyrosinase nationallicence Thioredoxin reductase nationallicence Schallreuter K. Department of Dermatology, University of Hamburg, Hamburg, FRG aut Wood J. Department of Biochemistry, Gray Freshwater Biological Institute, University of Minnesota, P. O. Box 100, Navarre, Minn., USA aut Archives of Dermatological Research Springer-Verlag 282/3(1990-05-01), 168-171 0340-3696 282:3<168 1990 282 403 https://doi.org/10.1007/BF00372617 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00372617 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Schallreuter K. Department of Dermatology, University of Hamburg, Hamburg, FRG aut NATIONALLICENCE 700 1- Wood J. Department of Biochemistry, Gray Freshwater Biological Institute, University of Minnesota, P. O. Box 100, Navarre, Minn., USA aut NATIONALLICENCE 773 0- Archives of Dermatological Research Springer-Verlag 282/3(1990-05-01), 168-171 0340-3696 282:3<168 1990 282 403 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer