title: Oxidative stress in vitiligo: photo-oxidation of pterins produces H(2)O(2) and pterin-6-carboxylic acid.
abstract: Patients with vitiligo accumulate millimolar levels of H(2)O(2) in their epidermis. The recycling process of (6R)-l-erythro-5,6,7,8-tetrahydrobiopterin in these patients is disrupted due to deactivation of 4a-OH-BH(4) dehydratase by H(2)O(2). The H(2)O(2) oxidation products 6- and 7-biopterin lead to the characteristic fluorescence of the affected skin upon Wood's light examination (UVA 351 nm). Here we report for the first time the presence and accumulation of pterin-6-carboxylic acid (P-6-COOH) in the epidermis of these patients. Exploring potential sources for P-6-COOH revealed that sepiapterin and 6-biopterin are readily photo-oxidised to P-6-COOH by UVA/UVB irradiation. Photolysis of sepiapterin and 6-biopterin produces stoichiometric H(2)O(2) under aerobic conditions, where O(2) is the electron acceptor, thus identifying an additional source for H(2)O(2) generation in vitiligo. A detailed analysis utilising UV/visible spectrophotometry, HPLC, TLC, and mass spectroscopy showed for sepiapterin direct oxidation to P-6-COOH, whereas 6-biopterin formed the intermediate 6-formylpterin (P-6-CHO) which is then further photo-oxidised to P-6-COOH.
authors.affiliation: Institute for Pigmentary Disorders in Association with Ernst-Moritz-Arndt University, Greifswald, Germany.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Rokos
authors.forename: Wayne D
authors.initials: WD
authors.lastname: Beazley
authors.forename: Karin U
authors.initials: KU
authors.lastname: Schallreuter
mesh_terms: D001708:Biopterins / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000528:radiation effects; D002374:Catalase / Q000378:metabolism / Q000494:pharmacology / Q000528:radiation effects; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D004817:Epidermis / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000528:radiation effects; D018384:Oxidative Stress; D010100:Oxygen / Q000737:chemistry; D010777:Photochemistry; D011621:Pteridines / Q000032:analysis / Q000737:chemistry / Q000378:metabolism* / Q000528:radiation effects; D011622:Pterins / Q000378:metabolism* / Q000528:radiation effects; D014466:Ultraviolet Rays; D014820:Vitiligo / Q000188:drug therapy / Q000378:metabolism*
chemical_list: D011621:Pteridines; D011622:Pterins; C405202:pterine-6-carboxylic acid; D001708:Biopterins; C005926:2-amino-4-hydroxy-6-formylpteridine; D006861:Hydrogen Peroxide; C016727:sepiapterin; C038109:pseudocatalase; D002374:Catalase; C003402:sapropterin; D010100:Oxygen