The role of sulfhydryl compounds in mammalian melanogenesis: the effect of cysteine glutathione upon tyrosinase the intermediates of the pathway

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aDpto. Bioquímica y Biología Molecular, Facultad de Medicina, Universidad de Murcia, Murcia Spain
Received 5 May 1988.
The effect of cysteine glutathione on mammalian melanogenesis has been studied. It has been shown that their action is mediated by two different mechanisms. (a) The reaction of the thiol groups with dopaquinone after the tyrosinase-catalyzed oxidation of tyrosine dopa. This mechanism leads to the formation of sulfhydryl-dopa conjugates finally sulfur-containing pigments, phaeomelanins instead of eumelanins. This fact might produce an inhibition of melanogenesis due to the slower rate of chemical reactions involved in the polymerization of such thiol-conjugates when compared to that of indoles. (b) The direct interaction between the sulfhydryl compounds the tyrosinase active site. This interaction may regulate the activity of the enzyme. It is shown that Harding-Passey mouse melanoma tyrosinase is more sensitive to sulfhydryl compounds than mushroom tyrosinase. Cysteine always produces an inhibition of the tyrosinase hydroxylase dopa oxidase activities of melanoma tyrosinase, this inhibition becoming greater as the cysteine concentration increases. On the other h, glutathione produces an activation of the tyrosine hydroxylase activity below 3 mM an inhibition at higher concentrations. The limit between the enzymatic activation inhibition appears at glutathione concentrations similar to the physiological levels of this compound found in melanocytes. Although the switch from eumelanogenesis to phaeomelanogenesis occurs at much lower concentrations of glutathione, taking into ac these data it is discussed that this sulfhydryl compound may regulate not only the type but also the amount of melanin formed inside melanocytes.
Keywords: Melanogenesis; Tyrosinase; Cysteine; Glutathione; Phaeomelanin
Abbreviations: BSA, bovine serum albumin; dopa, 3,4-dihydroxyphenylalanine; DTNB, 5,5′-dithiobis(2-nitrobenzoic acid); PMSF, phenylmethylsulfonyl fluoride; dimethyl-POPOP, 1,4-bis-[4-methyl-5-phenyl-2-oxazolyl]benzene, PPO, 2,5-diphenyloxazole

Correspondence: F. Solano, Dpto. Bioquímica y Biología Molecular, Facultad de medicina, Universidad de Murcia, Murcia 30100, Spain.
含巯基化合物在哺乳动物色素形成中的生化角色
半胱氨酸、谷胱甘肽在对铬氨酸酶形成色素及中间产物的影响
1988,5月    穆尔西亚大学医学院，穆尔西亚，西班牙
摘要
本文研究半胱氨酸及谷胱甘肽对哺乳动物体内中色素产生过程中的影响机制。影响机制分为以下两类：① 半胱氨酸及谷胱甘肽内的巯基与铬氨酸经由铬氨酸酶催化与Dopa合成产生的色素中间体Dopaquinone作用形成巯基Dope，形成另一中间产物。这个作用干扰并阻止真黑色素的形成。② 巯基与铬氨酸酶上有效催化作用的位置产生化学作用，因而降低铬氨酸酶的催化作用，从而降低铬氨酸转变为色素的化学作用速度。半胱氨酸及谷胱甘肽两者都明显的随着浓度增加而有效的延缓并阻断色素种类及数量的形成。