Acetaldehyde adducts with hemoglobin

• Published in: The Journal of clinical investigation Vol. 67; no. 2; pp. 361 - 369
• Main Authors: Stevens, V J, Fantl, W J, Newman, C B, Sims, R V, Cerami, A, Peterson, C M
• Format: Journal Article
• Language: English
• Published: United States 01.02.1981
• Subjects: Acetaldehyde - metabolism; Acetaldehyde - pharmacology; Alcoholism - blood; Amino Acids - analysis; Chromatography, High Pressure Liquid; Chromatography, Ion Exchange; Erythrocytes - drug effects; Globins - analysis; Hemoglobin A - metabolism; Humans; Oxidation-Reduction; Radioimmunoassay
• ISSN: 0021-9738
• DOI: 10.1172/JCI110043

Clinical studies on the minor hemoglobins (hemoglobin A1a-c) have suggested that a novel adduct may form in people abusing alcohol. Such patients were found to have an elevated concentration of minor hemoglobins, but normal or subnormal amounts of glycosylated hemoglobin (hemoglobin A1c) as determined by radioimmunoassay, Acetaldehyde, a reactive metabolite of ethanol, was postulated to form adducts with hemoglobin A that change its chromatographic properties. At physiological concentrations, acetaldehyde was found to form adducts with hemoglobin that were stable to extensive dialysis for several days. The amount of hemoglobin adducts formed were a function of the concentration and number of exposures to acetaldehyde. The reaction of acetaldehyde with hemoglobin A produced chromatographic variants, some of which migrated in the hemoglobin A1a-c region. Analysis of stable acetaldehyde-hemoglobin adducts demonstrated that valine, lysine, and tyrosine residues of globin were sites of reaction. The acetaldehyde-modified amino acid residues appear to exist in interconvertible conformations, only one of which is reducible by sodium borohydride. The amount of these adducts was found to be significantly elevated in hemoglobin from alcoholics as compared with normal volunteers.