Klevay L M
Department of Internal Medicine, University of North Dakota, Grand Forks, ND 58201, USA.
Cell Mol Biol (Noisy-le-grand). 2006 Dec 31;52(5):11-5.
Four classes of agents capable of producing human illness have been identified: toxicity, heredity, infection and deficiency. Examples of how members of these classes of etiologic agents can cooperate to produce illness were shown. The copper deficiency theory of ischemic heart disease and the homocysteine theory of arteriosclerosis were examined using concepts about cooperation. The Western diet so closely associated with these illnesses often is low in copper. Copper deficiency decreases the activity of methionine synthase which contributes to elevation of homocysteine, and of paraoxonase which impairs hydrolysis of homocysteine thiolactone, an inhibitor of lysyl oxidase. This copper-dependent enzyme initiates the cross-linking of collagen and elastin in arteries and bone. High homocysteine also impairs superoxide dismutase, a copper-dependent enzyme important in oxidative defense. Some genes affecting paraoxonase activity may respond to dietary copper. The copper deficiency theory of ischemic heart disease and the homocysteine theory of arteriosclerosis are inextricably entwined.
毒性、遗传、感染和缺乏。文中展示了这些病因类别中的因素如何相互协作导致疾病的实例。运用协作的概念对缺血性心脏病的铜缺乏理论和动脉粥样硬化的同型半胱氨酸理论进行了研究。与这些疾病密切相关的西方饮食通常铜含量较低。铜缺乏会降低甲硫氨酸合成酶的活性，该酶会导致同型半胱氨酸水平升高；还会降低对氧磷酶的活性，该酶会损害同型半胱氨酸硫内酯（一种赖氨酰氧化酶抑制剂）的水解。这种依赖铜的酶启动动脉和骨骼中胶原蛋白和弹性蛋白的交联。高同型半胱氨酸水平还会损害超氧化物歧化酶，这是一种在氧化防御中起重要作用的依赖铜的酶。一些影响对氧磷酶活性的基因可能会对膳食铜产生反应。缺血性心脏病的铜缺乏理论和动脉粥样硬化的同型半胱氨酸理论紧密相连。
