Tetrahydrobiopterin Photooxidation: a Key Process in Vitiligo Phototherapy

The processes of the autooxidation and photooxidation of tetrahydrobiopterin (H(4)Bip) (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 H(4)Bip autooxidation and analysis of the reaction products via high-performance liquid chromatography (HPLC) demonstrated that autooxidation was intensive at a rate constant of 1 x 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 H(4)Bip in melanocytes obviously triggers an autocatalytic cycle of the synthesis of the excess of hydrogen peroxide (H2O2). This, in turn, activates interferon-inducible GTP cyclohydrolase, which synthesizes an excess of H(4)Bip. The autocatalytic cycle of excess H2O2 synthesis apparently underlies the pathology of vitiligo. The excess H2O2 is also partly spent to activate the immune system. The autocatalytic cycle can be broken via the conversion of H(4)Bip into dihydropterin dimers during its UV photooxidation. The kinetics of H(4)Bip 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.

Automated summary

The study revealed that the excess oxidation of H(4)Bip in melanocytes triggers an autocatalytic cycle of hydrogen peroxide synthesis, leading to activation of the immune system in vitiligo. UV photooxidation can disrupt this cycle, making the range of 300-325 nm efficient for vitiligo phototherapy.