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: Hartmut Rokos, Wayne D Beazley, Karin U Schallreuter
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 292 Issue 4 Pg. 805-11 (Apr 12 2002) ISSN: 0006-291X [Print] United States
• PMID: 11944885 (Publication Type: Clinical Trial, Controlled Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: (c)2002 Elsevier Science (USA).

Chemical References

• Pteridines
• Pterins
• pterine-6-carboxylic acid
• Biopterin
• 2-amino-4-hydroxy-6-formylpteridine
• Hydrogen Peroxide
• sepiapterin
• pseudocatalase
• Catalase
• sapropterin
• Oxygen

Topics

• Biopterin (analogs & derivatives, chemistry, metabolism, radiation effects)
• Catalase (metabolism, pharmacology, radiation effects)
• Chromatography, High Pressure Liquid
• Chromatography, Thin Layer
• Epidermis (chemistry, drug effects, metabolism)
• Humans
• Hydrogen Peroxide (analysis, chemistry, metabolism)
• Oxidation-Reduction (radiation effects)
• Oxidative Stress
• Oxygen (chemistry)
• Photochemistry
• Pteridines (analysis, chemistry, metabolism, radiation effects)
• Pterins (metabolism, radiation effects)
• Ultraviolet Rays
• Vitiligo (drug therapy, metabolism)