The role of photochemical transformations of tetrahydrobiopterin in the pathogenesis and phototherapy of vitiligo

Abstract

Melanogenesis disorder leads to several pathologies, including vitiligo. Tetrahydrobiopterin (H4Bip) as the phenylalanine 4-hydroxylase coenzyme catalyzes the oxidation of phenylalanine to tyrosine (a melanin precursor). H4Bip is easily oxidized by oxygen in vivo and in vitro. Vitiligo is accompanied by three-fivefold increased de-novo synthesis of H4Bip, its excess and its further oxidation are essential factors in the pathogenesis of vitiligo. We have demonstrated that pterin products of H4Bip autoxidation (dihydropterin (H2Ptr), dihydroxanthopterin and pterin) predominate over biopterin products (dihydrobiopterin (H2Bip) and biopterin). It was shown that ultraviolet (UV) irradiation accelerates the autoxidation while the products of oxidative degradation of H4Bip act as photosensitizers. Photosensitized oxidation of H4Bip can contribute to the pathogenesis of vitiligo. The main distinguishing feature of UV photooxidation of H4Bip from autoxidation was the formation of dihydropterin (Н2Ptr)2 and dihydrobiopterin (Н2Bip)2 dimers. Here we reported on the dependences of the photodimerization reaction on the wavelength and intensity of radiation using xenon lamps and UV tunable lasers as sources of UV radiation. It was shown that UV irradiation with a laser is more efficient than that with xenon lamp. It was established that the greatest number of dimers were formed by irradiating the H4Bip solution by radiation with a wavelength in the range 308-312 nm. The data obtained are discussed in the context of UVB narrowband vitiligo phototherapy.