Tetrahydrobiopterin as a Trigger for Vitiligo: Phototransformation during UV Irradiation.
Taisiya A TeleginaYuliya L VechtomovaVera A BorzovaAndrey A BuglakPublished in: International journal of molecular sciences (2023)
Vitiligo is a type of hypomelanosis. Tetrahydrobiopterin (H 4 Bip), the coenzyme of the initial stage of melanogenesis, appears to be a trigger for vitiligo. H 4 Bip is present in vitiligo in 3-5-fold excess and causes oxidative stress by triggering an autocatalytic cycle of excess hydrogen peroxide synthesis. Using quantum-chemical calculations, we have evaluated the possibility of H 4 Bip reactions occurring in the dark and under ultraviolet (UV) irradiation, including the formation of dihydropterin dimers. In order to simulate the oxidative stress, oxidative modification of human serum albumin (HSA) has been carried out in the presence of excessive H 4 Bip using the fluorescence method. The fraction of oxidized protein (FOP) has been calculated. It has been established that there is a strong oxidative modification of amino acids chromophores (tryptophan and tyrosine) in the protein (FOP 0.64). Under UV irradiation of the system (HSA + H 4 Bip), FOP is reduced to 0.39. Apparently, a part of H 4 Bip transforms into dihydropterin dimers and does not participate in the oxidative modification of the protein. The data on oxidative modification of HSA are consistent with dynamic light scattering: H 4 Bip promotes HSA aggregation with the formation of particles with a hydrodynamic radius R h ≥ 2000 nm, which can become immunogenic.
Keyphrases
- hydrogen peroxide
- oxidative stress
- amino acid
- protein protein
- human serum albumin
- nitric oxide
- dna damage
- molecular dynamics
- binding protein
- radiation induced
- small molecule
- radiation therapy
- molecular dynamics simulations
- density functional theory
- body mass index
- deep learning
- weight gain
- physical activity
- aqueous solution
- data analysis
- artificial intelligence
- heat stress
- light emitting