Garcia-Jimenez Antonio, Teruel-Puche Jose Antonio, Garcia-Ruiz Pedro Antonio, Berna Jose, Rodríguez-López Jose Neptuno, Tudela Jose, Garcia-Canovas Francisco
GENZ-Group of Research on Enzymology(1), Department of Biochemistry and Molecular Biology-A, Regional Campus of International Excellence "Campus Mare Nostrum", University of Murcia, E-30100, Espinardo, Murcia, Spain.
Group of Molecular Interactions in Membranes, Department of Biochemistry and Molecular Biology-A, University of Murcia, E-30100, Espinardo, Murcia, Spain.
Int J Biol Macromol. 2017 May;98:622-629. doi: 10.1016/j.ijbiomac.2017.02.032. Epub 2017 Feb 10.
2,2',4,4'-tetrahydroxybenzophenone (Uvinul D50), a sunscreen used in cosmetics, has two effects in the melanin biosynthesis pathway. On the one hand, it acts a weak inhibitor of tyrosinase and on the other, it accelerates the conversion of dopachrome to melanin. Uvinul D50 was seen to behave as a weak competitive inhibitor: apparent constant inhibition=2.02±0.09mM and IC50=3.82±0.39mM established in this work. These values are higher than those in the bibliography, which tend to be undersetimated. This discrepancy could be explained by the reaction of Uvinul D50 with the dopachrome produced from l-tyrosine or l-dopa, which would interfere in the measurement. Based on studies of its docking to tyrosinase, it seems that Uvinul D50 interacts with the active site of the enzyme (oxytyrosinase) both in its protonated and deprotonated forms (pKa=7). However, it cannot be hydroxylated, meaning that it acts as a weak inhibitor, not as an alternative substrate, despite its resorcinol structure. Uvinul D50 can be used as sunscreen, in low concentrations without significant adverse effects on melanogenesis.
2,2',4,4'-四羟基二苯甲酮（Uvinul D50）是一种用于化妆品的防晒剂，在黑色素生物合成途径中有两种作用。一方面，它是一种弱酪氨酸酶抑制剂；另一方面，它加速多巴色素向黑色素的转化。在本研究中，Uvinul D50表现为一种弱竞争性抑制剂：表观抑制常数=2.02±0.09mM，IC50=3.82±0.39mM。这些值高于文献中的值，文献中的值往往被低估。这种差异可以用Uvinul D50与由L-酪氨酸或L-多巴产生的多巴色素的反应来解释，这会干扰测量。基于其与酪氨酸酶对接的研究，Uvinul D50似乎在其质子化和去质子化形式（pKa=7）下均与该酶（氧化型酪氨酸酶）的活性位点相互作用。然而，它不能被羟基化，这意味着尽管它具有间苯二酚结构，但它作为一种弱抑制剂起作用，而不是作为替代底物。Uvinul D50可以用作防晒剂，低浓度使用时对黑色素生成没有明显的不良影响。
