title: Homocysteine, iron and cardiovascular disease: a hypothesis.
abstract: Elevated circulating total homocysteine (tHcy) concentrations (hyperhomocysteinemia) have been regarded as an independent risk factor for cardiovascular disease (CVD). However, several large clinical trials to correct hyperhomocysteinemia using B-vitamin supplements (particularly folic acid) have largely failed to reduce the risk of CVD. There is no doubt that a large segment of patients with CVD have hyperhomocysteinemia; therefore, it is reasonable to postulate that circulating tHcy concentrations are in part a surrogate marker for another, yet-to-be-identified risk factor(s) for CVD. We found that iron catalyzes the formation of Hcy from methionine, S-adenosylhomocysteine and cystathionine. Based on these findings, we propose that an elevated amount of non-protein-bound iron (free Fe) increases circulating tHcy. Free Fe catalyzes the formation of oxygen free radicals, and oxidized low-density lipoprotein is a well-established risk factor for vascular damage. In this review, we discuss our findings on iron-catalyzed formation of Hcy from thioethers as well as recent findings by other investigators on this issue. Collectively, these support our hypothesis that circulating tHcy is in part a surrogate marker for free Fe, which is one of the independent risk factors for CVD.
authors: Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL 35294, USA. marilynbaggott@att.net.
authors: Joseph E
authors: JE
authors: Baggott
authors: Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL 35294, USA. tamurat@uab.edu.
authors: Tsunenobu
authors: T
authors: Tamura
mesh_terms: D015415:Biomarkers / Q000097:blood*; D002318:Cardiovascular Diseases / Q000097:blood* / Q000209:etiology / Q000378:metabolism; D003540:Cystathionine / Q000378:metabolism; D019587:Dietary Supplements; D005492:Folic Acid / Q000494:pharmacology; D005609:Free Radicals / Q000378:metabolism; D006710:Homocysteine / Q000378:metabolism*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000178:diet therapy / Q000378:metabolism; D007501:Iron / Q000097:blood* / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D008715:Methionine / Q000378:metabolism; D012307:Risk Factors; D012435:S-Adenosylhomocysteine / Q000378:metabolism; D014803:Vitamin B Complex / Q000494:pharmacology
chemical_list: D015415:Biomarkers; D005609:Free Radicals; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D006710:Homocysteine; D014803:Vitamin B Complex; D003540:Cystathionine; D005492:Folic Acid; D012435:S-Adenosylhomocysteine; D008715:Methionine; D007501:Iron