title: How dietary deficiency, genes and a toxin can cooperate to produce arteriosclerosis and ischemic heart disease.
abstract: 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.
authors.affiliation: Department of Internal Medicine, University of North Dakota, Grand Forks, ND 58201, USA. leslie_klevay@und.nodak.edu
authors.forename: L M
authors.initials: LM
authors.lastname: Klevay
mesh_terms: D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology* / Q000503:physiopathology; D043303:Aryldialkylphosphatase / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D003300:Copper / Q000378:metabolism; D004032:Diet; D004549:Elastin / Q000378:metabolism; D006331:Heart Diseases / Q000209:etiology / Q000503:physiopathology; D006710:Homocysteine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity; D006801:Humans; D044342:Malnutrition / Q000150:complications*; D017202:Myocardial Ischemia / Q000209:etiology* / Q000503:physiopathology
chemical_list: D006710:Homocysteine; D003300:Copper; D003094:Collagen; D004549:Elastin; C007957:homocysteine thiolactone; D043303:Aryldialkylphosphatase