Pavel S
Department of Dermatology, University Hospital, Leiden, The Netherlands.
J Invest Dermatol. 1993 Feb;100(2 Suppl):162S-165S.
The course of melanogenesis in (malignant) melanocytes is determined by several relatively independent metabolic processes such as tyrosine uptake and compartmentation, the activity of tyrosinase, and the capacity of melanosomes to produce and store melanin. There is experimental evidence that tyrosine is transported across the cell membrane with a Na(+)-independent L transport system. Tyrosine designated for melanogenesis is probably localized in compartments different from those for protein synthesis. The maturation and subsequent activation of tyrosinase occurs primarily in the Golgi-associated endoplasmatic reticulum and coated vesicles. In these locations, the interaction between tyrosine and tyrosinase has some limitations because no melanin polymer can be detected in these structures. Nevertheless, the coated vesicles were shown to contain unpolymerized monomeric indols. Individual skin types differ in their ability to produce mature, fully pigmented, melanosomes. Whereas eumelanin content in melanocytes corresponds to the phenotypic appearance of the skin, the formation of pheomelanin varies considerably. Precursors of pheomelanin, such as glutathione and cysteine, are responsible for scavenging potentially toxic quinoid products of melanogenesis that escape from melanogenic compartments. Pheomelanogenesis can therefore be considered as one of the protective mechanisms of melanocytes. Significant leakage of reactive intermediates of melanogenesis may occur from aberrant melanosomes and explain the frequent incidence of necrosis in melanoma tissue. The presence of O-methylated derivatives of 5,6-dihydroxyindole (5,6DHI) and 5,6-dihydroxyindole-2-carboxylic acid (5,6DHI2C) in medium of melanoma cell cultures gives evidence of intracellular O-methylating ability. The O-methylation of o-dihydroxyphenols and indols by catechol-O-methyltransferase localized in microsomes and cytoplasma prevents their oxidation to reactive quinones. It is suggested, however, that this protective mechanism can be unreliable because catechol-O-methyltransferase can be inactivated by its oxidated substrates.
（恶性）黑素细胞中黑色素生成的过程由几个相对独立的代谢过程决定，如酪氨酸摄取和区室化、酪氨酸酶的活性以及黑素小体产生和储存黑色素的能力。有实验证据表明，酪氨酸通过一种不依赖Na⁺的L转运系统跨细胞膜运输。用于黑色素生成的酪氨酸可能定位于与蛋白质合成不同的区室。酪氨酸酶的成熟及随后的激活主要发生在与高尔基体相关的内质网和被膜小泡中。在这些位置，酪氨酸与酪氨酸酶之间的相互作用存在一些限制，因为在这些结构中检测不到黑色素聚合物。然而，被膜小泡显示含有未聚合的单体吲哚。不同的皮肤类型在产生成熟、完全色素化的黑素小体的能力上存在差异。虽然黑素细胞中真黑素的含量与皮肤的表型外观相对应，但褐黑素的形成差异很大。褐黑素的前体，如谷胱甘肽和半胱氨酸，负责清除从黑色素生成区室逸出的潜在有毒的黑色素生成醌类产物。因此，褐黑素生成可被视为黑素细胞的一种保护机制。黑色素生成的反应性中间体可能从异常的黑素小体中大量泄漏，这解释了黑色素瘤组织中坏死的频繁发生。黑色素瘤细胞培养介质中存在5,6 - 二羟基吲哚（5,6DHI）和5,6 - 二羟基吲哚 - 2 - 羧酸（5,6DHI2C）的O - 甲基化衍生物，这证明了细胞内的O - 甲基化能力。位于微粒体和细胞质中的儿茶酚 - O - 甲基转移酶对邻二羟基酚和吲哚的O - 甲基化可防止它们氧化为反应性醌。然而，有人认为这种保护机制可能不可靠，因为儿茶酚 - O - 甲基转移酶可能会被其氧化底物灭活。
