Tetrahydrobiopterin Photooxidation: a Key Process in Vitiligo Phototherapy

Abstract

Abstract: The processes of the autooxidation and photooxidation of tetrahydrobiopterin (Н4Bip) (a coenzyme present in a three- to fivefold excess in vitiligo) were studied in the context of vitiligo pathology and treatment. The study of the kinetics of Н4Bip autooxidation and analysis of the reaction products via high-performance liquid chromatography (HPLC) demonstrated that autooxidation was intensive at a rate constant of 1 × 10–3 s–1 with the formation of dihydrobiopterin, dihydropterin, and their oxidized derivatives. Analysis of the autooxidation data led to a new conclusion that the oxidation of the excess of Н4Bip in melanocytes obviously triggers an autocatalytic cycle of the synthesis of the excess of hydrogen peroxide (Н2О2). This, in turn, activates interferon-inducible GTP cyclohydrolase, which synthesizes an excess of Н4Bip. The autocatalytic cycle of excess Н2О2 synthesis apparently underlies the pathology of vitiligo. The excess Н2О2 is also partly spent to activate the immune system. The autocatalytic cycle can be broken via the conversion of Н4Bip into dihydropterin dimers during its UV photooxidation. The kinetics of Н4Bip was studied, the reaction products were identified, and the quantum yields of the formation of dihydropterin dimers were calculated. The action spectrum of UV radiation was constructed based on the quantum yield data. It shows that the range of 300–325 nm is efficient for vitiligo phototherapy.