Iron-dependent formation of homocysteine from methionine and other thioethers

• Published in: European journal of clinical nutrition Vol. 61; no. 12; pp. 1359 - 1363
• Main Authors: Baggott, J.E, Tamura, T
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.12.2007; Nature Publishing; Nature Publishing Group
• Subjects: Acids; Adult; adults; Aerobic conditions; Area Under Curve; Biological and medical sciences; biosynthesis; Body weight; chelating agents; chelation; chemical reactions; Clinical Nutrition; Cross-Over Studies; Cystathionine; Cystathionine - metabolism; dietary minerals; Epidemiology; ethers; Feeding. Feeding behavior; Female; Ferrous sulfate; Fundamental and applied biological sciences. Psychology; Homocysteine; Homocysteine - biosynthesis; Humans; Hydrogen-Ion Concentration; in vitro studies; In vivo methods and tests; Incubation; Internal Medicine; Iron; Iron - metabolism; Iron Chelating Agents; Iron Chelating Agents - pharmacology; Iron sulfates; Male; Medical sciences; Medicine; Medicine & Public Health; Metabolic Diseases; metabolism; Methionine; Methionine - metabolism; Nutrition; nutrition physiology; original-article; pH effects; pharmacology; Plasma; Public Health; S-Adenosylhomocysteine; S-Adenosylhomocysteine - metabolism; Sulfates; Thioethers; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vitamin B; United States > US; homocysteine; methionine; human; iron-dependent chemical reactions; thioethers; Human; Thiol; Nutrition; Methionine; Metabolic diseases; Iron; Reaction; Inorganic element; Sulfur containing aminoacid; Homocystein; Chemical reaction; Formation
• ISSN: 0954-3007; 1476-5640
• DOI: 10.1038/sj.ejcn.1602665

Objective: We tested whether homocysteine is formed from methionine and other thioethers in vitro and in vivo, because methionine can be chemically demethylated to homocysteine. Design: In in vitro studies, chemical conversions of thioethers (methionine, S-adenosylhomocysteine and cystathionine) into homocysteine were measured under various aerobic conditions. In humans, oral methionine (0.17 mmol/kg body weight) loading tests with and without an oral iron dose (ferrous sulfate, 13 mol/kg) were performed. Setting: A university setting in Birmingham, AL, USA. Subjects: A total of five healthy adult subjects volunteered. Results: The in vitro incubation of methionine, S-adenosylhomocysteine or cystathionine with chelated iron resulted in the formation of homocysteine. These conversions were iron- and pH-dependent (pH optima between 5.0 and 6.0) and it was also chelator-dependent. In humans, oral methionine loading tests resulted in a 45% increase in the area-under-the-curve for plasma total homocysteine concentrations, when iron was given together with methionine. Conclusion: Our data suggest that iron-dependent chemical formation of homocysteine can occur in vivo, and contribute to the plasma total homocysteine pool, since this formation can occur ceaselessly. We hypothesize that plasma total homocysteine concentrations reflect, in part, non-protein-bound iron in the body.