THE ROLE OF SULFHYDRYL COMPOUNDS IN MAMMALIAN MELANOGENESIS - THE EFFECT OF CYSTEINE AND GLUTATHIONE UPON TYROSINASE AND THE INTERMEDIATES OF THE PATHWAY
THE ROLE OF SULFHYDRYL COMPOUNDS IN MAMMALIAN MELANOGENESIS - THE EFFECT OF CYSTEINE AND GLUTATHIONE UPON TYROSINASE AND THE INTERMEDIATES OF THE PATHWAY
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DOI：
10.1016/0304-4165(88)90023-2
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发表时间：
1988-11-17
期刊：
影响因子：
--
通讯作者：
LOZANO, JA
中科院分区：
文献类型：
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作者：
JARA, JR;AROCA, P;LOZANO, JA
半胱氨酸和谷胱甘肽对哺乳动物黑素生成的影响已被研究。研究表明，它们的作用是由两种不同的机制介导的。 (a)酪氨酸酶催化酪氨酸和多巴氧化后，硫醇基团与多巴醌的反应。这种机制导致形成巯基-多巴缀合物，并最终形成含硫色素、褐黑素而不是乳黑素。这一事实可能会抑制黑素生成，因为与吲哚相比，此类硫醇缀合物聚合中涉及的化学反应速率较慢。 (b) 巯基化合物和酪氨酸酶活性位点之间的直接相互作用。这种相互作用可以调节酶的活性。结果表明，Harding-Passey 小鼠黑色素瘤酪氨酸酶比蘑菇酪氨酸酶对巯基化合物更敏感。半胱氨酸总是对黑色素瘤酪氨酸酶的酪氨酸酶羟化酶和多巴氧化酶活性产生抑制作用，这种抑制作用随着半胱氨酸浓度的增加而变得更大。另一方面，谷胱甘肽在低于 3 mM 时会激活酪氨酸羟化酶活性，而在较高浓度时会产生抑制作用。酶激活和抑制之间的限制出现在与黑素细胞中发现的该化合物的生理水平相似的谷胱甘肽浓度处。尽管从真黑素生成到褐黑素生成的转变发生在谷胱甘肽浓度低得多的情况下，但考虑到这些数据，人们讨论这种巯基化合物不仅可以调节黑素细胞内形成的黑色素的类型，还可以调节其数量。
The effect of cysteine and glutathione on mammalian melanogenesis has been studied. It has been shown that their action is mediated by two different mechansims. (a) The reaction of the thiol groups with dopaquinone after the tyrosinase-catalyzed oxidation of tyrosine and dopa. This mechanism leads to the formation of sulfhydryl-dopa conjugates and finally sulfur-containing pigments, phaeomelanins instead of emuelanins. 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 and 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 and dopa oxidase activities of melanoma tyrosinase, this inhibition becoming greater as the cysteine concentration increases. On the other hand, gluthathione produces an activation of the tyrosine hydroxylase activity below 3 mM and an inhibition at higher concentrations. The limit between the enzymatic activation and inhibition appears at glutathione concentrations similar to the physiological levels of this compound found in melanocytes. Although the switch from eumelanogenesis to phaeomelangoensis occurs at much lower concentrations of glutathione, taking into account these data it is discussed that this sulfhydryl compound may regulate not only the type but also the amount of melanin formed inside melanocytes.