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. 1981 Feb;67(2):361–369. doi: 10.1172/JCI110043

Acetaldehyde adducts with hemoglobin.

V J Stevens, W J Fantl, C B Newman, R V Sims, A Cerami, C M Peterson
PMCID: PMC370576  PMID: 7462422

Abstract

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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Benesch R. E., Edalji R., Kwong S., Benesch R. Oxygen affinity as an index of hemoglobin S polymerization: a new micromethod. Anal Biochem. 1978 Aug 15;89(1):162–173. doi: 10.1016/0003-2697(78)90737-6. [DOI] [PubMed] [Google Scholar]
  2. Blass J., Bizzini B., Raynaud M. Mécanisme de la détoxification par le formol. C R Acad Sci Hebd Seances Acad Sci D. 1965 Aug 2;261(5):1448–1449. [PubMed] [Google Scholar]
  3. Bookchin R. M., Gallop P. M. Structure of hemoglobin AIc: nature of the N-terminal beta chain blocking group. Biochem Biophys Res Commun. 1968 Jul 11;32(1):86–93. doi: 10.1016/0006-291x(68)90430-0. [DOI] [PubMed] [Google Scholar]
  4. Bunn H. F., Haney D. N., Gabbay K. H., Gallop P. M. Further identification of the nature and linkage of the carbohydrate in hemoglobin A1c. Biochem Biophys Res Commun. 1975 Nov 3;67(1):103–109. doi: 10.1016/0006-291x(75)90289-2. [DOI] [PubMed] [Google Scholar]
  5. Cerami A., Stevens V. J., Monnier V. M. Role of nonenzymatic glycosylation in the development of the sequelae of diabetes mellitus. Metabolism. 1979 Apr;28(4 Suppl 1):431–437. doi: 10.1016/0026-0495(79)90051-9. [DOI] [PubMed] [Google Scholar]
  6. Clegg J. B., Naughton M. A., Weatherball D. J. Abnormal human haemoglobins. Separation and characterization of the alpha and beta chains by chromatography, and the determination of two new variants, hb Chesapeak and hb J (Bangkok). J Mol Biol. 1966 Aug;19(1):91–108. doi: 10.1016/s0022-2836(66)80052-9. [DOI] [PubMed] [Google Scholar]
  7. Cole R. A., Soeldner J. S., Dunn P. J., Bunn H. F. A rapid method for the determination of glycosylated hemoglobins using high pressure liquid chromatography. Metabolism. 1978 Mar;27(3):289–301. doi: 10.1016/0026-0495(78)90109-9. [DOI] [PubMed] [Google Scholar]
  8. Eriksson C. J. Elevated blood acetaldehyde levels in alcoholics and their relatives: a reevaluation. Science. 1980 Mar 21;207(4437):1383–1384. doi: 10.1126/science.7355298. [DOI] [PubMed] [Google Scholar]
  9. Eriksson C. J., Sippel H. W., Forsander O. A. The determination of acetaldehyde in biological samples by head-space gas chromatography. Anal Biochem. 1977 May 15;80(1):116–124. doi: 10.1016/0003-2697(77)90631-5. [DOI] [PubMed] [Google Scholar]
  10. Gaines K. C., Salhany J. M., Tuma D. J., Sorrell M. F. Reaction of acetaldehyde with human erythrocyte membrane proteins. FEBS Lett. 1977 Mar 15;75(1):115–119. doi: 10.1016/0014-5793(77)80065-3. [DOI] [PubMed] [Google Scholar]
  11. Gonen B., Rubenstein A., Rochman H., Tanega S. P., Horwitz D. L. Haemoglobin A1: An indicator of the metabolic control of diabetic patients. Lancet. 1977 Oct 8;2(8041):734–737. doi: 10.1016/s0140-6736(77)90237-9. [DOI] [PubMed] [Google Scholar]
  12. Haney D. N., Bunn H. F. Glycosylation of hemoglobin in vitro: affinity labeling of hemoglobin by glucose-6-phosphate. Proc Natl Acad Sci U S A. 1976 Oct;73(10):3534–3538. doi: 10.1073/pnas.73.10.3534. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Javid J., Pettis P. K., Koenig R. J., Cerami A. Immunologic characterization and quantification of haemoglobin A1c. Br J Haematol. 1978 Mar;38(3):329–337. doi: 10.1111/j.1365-2141.1978.tb01051.x. [DOI] [PubMed] [Google Scholar]
  14. Koenig R. J., Blobstein S. H., Cerami A. Structure of carbohydrate of hemoglobin AIc. J Biol Chem. 1977 May 10;252(9):2992–2997. [PubMed] [Google Scholar]
  15. Koenig R. J., Peterson C. M., Jones R. L., Saudek C., Lehrman M., Cerami A. Correlation of glucose regulation and hemoglobin AIc in diabetes mellitus. N Engl J Med. 1976 Aug 19;295(8):417–420. doi: 10.1056/NEJM197608192950804. [DOI] [PubMed] [Google Scholar]
  16. Koenig R. J., Peterson C. M., Kilo C., Cerami A., Williamson J. R. Hemoglobin AIc as an indicator of the degree of glucose intolerance in diabetes. Diabetes. 1976 Mar;25(3):230–232. doi: 10.2337/diab.25.3.230. [DOI] [PubMed] [Google Scholar]
  17. Korsten M. A., Matsuzaki S., Feinman L., Lieber C. S. High blood acetaldehyde levels after ethanol administration. Difference between alcoholic and nonalcoholic subjects. N Engl J Med. 1975 Feb 20;292(8):386–389. doi: 10.1056/NEJM197502202920802. [DOI] [PubMed] [Google Scholar]
  18. Krebs H. A., Perkins J. R. The physiological role of liver alcohol dehydrogenase. Biochem J. 1970 Jul;118(4):635–644. doi: 10.1042/bj1180635. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. MOHAMMAD A., OLCOTT H. S., FRAENKEL-CONRAT H. The reaction of proteins with acetaldehyde. Arch Biochem. 1949 Dec;24(2):270–280. [PubMed] [Google Scholar]
  20. Peterson C. M., Jones R. L. Minor hemoglobins, diabetic "control", and diseases of postsynthetic protein modification. Ann Intern Med. 1977 Oct;87(4):489–491. doi: 10.7326/0003-4819-87-4-489. [DOI] [PubMed] [Google Scholar]
  21. Schwartz B. A., Gray G. R. Proteins containing reductively aminated disaccharides. Synthesis and chemical characterization. Arch Biochem Biophys. 1977 Jun;181(2):542–549. doi: 10.1016/0003-9861(77)90261-2. [DOI] [PubMed] [Google Scholar]
  22. Stevens V. J., Vlassara H., Abati A., Cerami A. Nonenzymatic glycosylation of hemoglobin. J Biol Chem. 1977 May 10;252(9):2998–3002. [PubMed] [Google Scholar]
  23. Stowell A. R., Greenway R. M., Batt R. D. Acetaldehyde formation during deproteinization of human blood samples containing ethanol. Biochem Med. 1977 Dec;18(3):392–401. doi: 10.1016/0006-2944(77)90075-8. [DOI] [PubMed] [Google Scholar]
  24. Trivelli L. A., Ranney H. M., Lai H. T. Hemoglobin components in patients with diabetes mellitus. N Engl J Med. 1971 Feb 18;284(7):353–357. doi: 10.1056/NEJM197102182840703. [DOI] [PubMed] [Google Scholar]
  25. Truitt E. B., Jr Ethanol-induced release of acetaldehyde from blood and its effect on the determination of acetaldehyde. Q J Stud Alcohol. 1970 Mar;31(1):1–12. [PubMed] [Google Scholar]

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