title: Chemical analysis of late stages of pheomelanogenesis: conversion of dihydrobenzothiazine to a benzothiazole structure.
abstract: Pheomelanogenesis is a complex pathway that starts with the oxidation of tyrosine (or DOPA, 3,4-dihydroxyphenylalanine) by tyrosinase in the presence of cysteine, which results in the production of 5-S-cysteinyldopa and its isomers. Beyond that step, relatively little has been clarified except for a possible intermediate produced, dihydro-1,4-benzothiazine-3-carboxylic acid (DHBTCA). We therefore carried out a detailed study on the course of pheomelanogenesis using DOPA and cysteine and the physiological enzyme tyrosinase. To elucidate the later stages of pheomelanogenesis, chemical degradative methods of reductive hydrolysis with hydroiodic acid and alkaline peroxide oxidation were applied. The results show that: (1) DHBTCA accumulates after the disappearance of the cysteinyldopa isomers, (2) DHBTCA is then oxidized by a redox exchange with dopaquinone to form ortho-quinonimine, which leads to the production of pheomelanin with a benzothiazine moiety, and (3) the benzothiazine moiety gradually degrades to form a benzothiazole moiety. This latter process is consistent with the much higher ratio of benzothiazole-derived units in human red hair than in mouse yellow hair. These findings may be relevant to the (photo)toxic effects of pheomelanin.
authors.affiliation: Department of Chemistry, Fujita Health University School of Health Sciences, Toyoake, Aichi, Japan.
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Wakamatsu
authors.forename: Kazumi
authors.initials: K
authors.lastname: Ohtara
authors.forename: Shosuke
authors.initials: S
authors.lastname: Ito
mesh_terms: D000143:Acids / Q000737:chemistry; D000409:Alanine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D052160:Benzothiazoles / Q000737:chemistry* / Q000378:metabolism; D003545:Cysteine / Q000737:chemistry / Q000378:metabolism; D003548:Cysteinyldopa / Q000737:chemistry / Q000378:metabolism; D004295:Dihydroxyphenylalanine / Q000737:chemistry* / Q000378:metabolism; D006200:Hair Color; D006801:Humans; D006868:Hydrolysis; D017613:Iodine Compounds / Q000737:chemistry; D008543:Melanins / Q000737:chemistry* / Q000378:metabolism; D051379:Mice; D014442:Monophenol Monooxygenase / Q000737:chemistry / Q000378:metabolism; D010084:Oxidation-Reduction; D010545:Peroxides / Q000737:chemistry; D013843:Thiazines / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000143:Acids; D052160:Benzothiazoles; D017613:Iodine Compounds; D008543:Melanins; D010545:Peroxides; D013843:Thiazines; C018362:pheomelanin; D003548:Cysteinyldopa; C068154:7-(3-carboxy-5-hydroxy-3,4-dihydro-2H-1,4-benzothiazinyl)alanine; D004295:Dihydroxyphenylalanine; C010466:hydroiodic acid; D014442:Monophenol Monooxygenase; D003545:Cysteine; D000409:Alanine