Rucker R B, Kosonen T, Clegg M S, Mitchell A E, Rucker B R, Uriu-Hare J Y, Keen C L
Department of Nutrition, University of California, Davis 95616, USA.
Am J Clin Nutr. 1998 May;67(5 Suppl):996S-1002S. doi: 10.1093/ajcn/67.5.996S.
Protein-lysine 6-oxidase (lysyl oxidase) is a cuproenzyme that is essential for stabilization of extracellular matrixes, specifically the enzymatic cross-linking of collagen and elastin. A hypothesis is proposed that links dietary copper levels to dynamic and proportional changes in lysyl oxidase activity in connective tissue. Although nutritional copper status does not influence the accumulation of lysyl oxidase as protein or lysyl oxidase steady state messenger RNA concentrations, the direct influence of dietary copper on the functional activity of lysyl oxidase is clear. The hypothesis is based on the possibility that copper efflux and lysyl oxidase secretion from cells may share a common pathway. The change in functional activity is most likely the result of posttranslational processing of lysyl oxidase. Copper is essential for organic cofactor formation in amine oxidases such as lysyl oxidase. Copper-containing amine oxidases have peptidyl 2,4,5 tri(oxo)phenylalanine (TOPA) at their active centers. TOPA is formed by copper-catalyzed oxidation of tyrosine, which takes place as part of Golgi or trans-Golgi processing. For lysyl oxidase, recent evidence (Science 1996;273:1078-84) indicates that as an additional step, a lysyl group at the active center of lysyl oxidase reacts with TOPA or its precursor to form lysyl tyrosylquinone.
蛋白质赖氨酸6-氧化酶（赖氨酰氧化酶）是一种铜酶，对细胞外基质的稳定至关重要，特别是对胶原蛋白和弹性蛋白的酶促交联。本文提出一个假说，将膳食铜水平与结缔组织中赖氨酰氧化酶活性的动态和比例变化联系起来。虽然营养性铜状态不影响赖氨酰氧化酶作为蛋白质的积累或赖氨酰氧化酶稳态信使RNA浓度，但膳食铜对赖氨酰氧化酶功能活性的直接影响是明显的。该假说基于细胞中铜外流和赖氨酰氧化酶分泌可能共享一条共同途径的可能性。功能活性的变化很可能是赖氨酰氧化酶翻译后加工的结果。铜对于胺氧化酶（如赖氨酰氧化酶）中有机辅因子的形成至关重要。含铜胺氧化酶在其活性中心含有肽基2,4,5-三（氧代）苯丙氨酸（TOPA）。TOPA是由铜催化的酪氨酸氧化形成的，这是高尔基体或反式高尔基体加工的一部分。对于赖氨酰氧化酶，最近的证据（《科学》1996年；273：1078 - 1084）表明，作为额外的一步，赖氨酰氧化酶活性中心的一个赖氨酰基团与TOPA或其前体反应形成赖氨酰酪氨酰醌。
