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. 1974 Mar;53(3):693–704. doi: 10.1172/JCI107607

Vitamin B6 Metabolism in Chronic Alcohol Abuse

PYRIDOXAL PHOSPHATE LEVELS IN PLASMA AND THE EFFECTS OF ACETALDEHYDE ON PYRIDOXAL PHOSPHATE SYNTHESIS AND DEGRADATION IN HUMAN ERYTHROCYTES

Lawrence Lumeng 1,2, Ting-Kai Li 1,2
PMCID: PMC333049  PMID: 4359937

Abstract

The plasma pyridoxal-5′-phosphate (PLP) level of alcoholic subjects has been compared with that of non-alcoholic individuals in order to ascertain the incidence of abnormal vitamin B6 metabolism in chronic alcohol abuse. 66 alcoholic subjects were selected on the basis that they did not exhibit abnormal liver function tests and hematologic findings. 35 of them had plasma PLP concentrations less than 5 ng/ml, the lowest value encountered in 94 control subjects, indicating a high incidence of deranged PLP metabolism in alcoholic patients even when hepatic and hematologic abnormalities are absent. The biochemical basis for the altered PLP metabolism in chronic alcohol abuse was examined. Low plasma PLP levels in alcoholics were not accompanied by decreased pyridoxal kinase and pyridoxine phosphate oxidase activities in erythrocytes. Further studies with erythrocytes demonstrated that the cellular content of PLP is determined not only by the activities of these PLP-synthesizing enzymes but also by the activity of a phosphate-sensitive, membrane-associated, neutral phosphatase, which hydrolyzes phosphorylated B6 compounds.

Acetaldehyde, but not ethanol, impaired the net formation of PLP from pyridoxal, pyridoxine, and pyridoxine phosphate by erythrocytes. However, when the B6-phosphate phosphatase activity was inhibited by 80 mM phosphate, this effect of acetaldehyde was abolished. By the use of broken cell preparations, it was possible to demonstrate directly that the action of acetaldehyde is mediated by the phosphatase, resulting in an acceleration of the degradation of the phosphorylated B6 compounds in erythrocytes.

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Selected References

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  1. Ammon H. P., Estler C. J., Heim F. Inactivation of coenzyme a by ethanol. I. Acetaldehyde as mediator of the inactivation of coenzyme A following the administration of ethanol in vivo. Biochem Pharmacol. 1969 Jan;18(1):29–33. doi: 10.1016/0006-2952(69)90005-7. [DOI] [PubMed] [Google Scholar]
  2. Anderson B. B., Fulford-Jones C. E., Child J. A., Beard M. E., Bateman C. J. Conversion of vitamin B 6 compounds to active forms in the red blood cell. J Clin Invest. 1971 Sep;50(9):1901–1909. doi: 10.1172/JCI106682. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chabner B., Livingston D. A simple enzymic assay for pyridoxal phosphate. Anal Biochem. 1970 Apr;34(2):413–423. doi: 10.1016/0003-2697(70)90126-0. [DOI] [PubMed] [Google Scholar]
  4. Colombini C. E., McCoy E. E. Vitamin B6 metabolism. The utilization of [14C]pyridoxine by the normal mouse. Biochemistry. 1970 Feb 3;9(3):533–538. doi: 10.1021/bi00805a012. [DOI] [PubMed] [Google Scholar]
  5. Duritz G., Truitt E. B., Jr Importance of acetaldehyde in the action of ethanol on brain norepinephrine and 5-hydroxytryptamine. Biochem Pharmacol. 1966 Jun;15(6):711–721. doi: 10.1016/0006-2952(66)90005-0. [DOI] [PubMed] [Google Scholar]
  6. Ebadi M. S., McCoy E. E., Kugel R. B. Interrelationships between pyridoxal phosphate and pyridoxal kinase in rabbit brain. J Neurochem. 1970 Jul;17(7):941–948. doi: 10.1111/j.1471-4159.1970.tb02247.x. [DOI] [PubMed] [Google Scholar]
  7. Eichner E. R., Hillman R. S. Effect of alcohol on serum folate level. J Clin Invest. 1973 Mar;52(3):584–591. doi: 10.1172/JCI107219. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Eichner E. R., Hillman R. S. The evolution of anemia in alcoholic patients. Am J Med. 1971 Feb;50(2):218–232. doi: 10.1016/0002-9343(71)90151-3. [DOI] [PubMed] [Google Scholar]
  9. Frank O., Luisada-Opper A., Sorrell M. F., Thomson A. D., Baker H. Vitamin deficits in severe alcoholic fatty liver of man calculated from multiple reference units. Exp Mol Pathol. 1971 Oct;15(2):191–197. doi: 10.1016/0014-4800(71)90098-0. [DOI] [PubMed] [Google Scholar]
  10. French S. W., Castagna J. Some effects of chronic ethanol feeding on vitamin B 6 deficiency in the rat. Lab Invest. 1967 Apr;16(4):526–531. [PubMed] [Google Scholar]
  11. GREENBERG L. D. ARTERIOSCLEROTIC, DENTAL AND HEPATIC LESIONS IN PYRIDOXINE-DEFICIENT MONKEYS. Vitam Horm. 1964;22:677–694. doi: 10.1016/s0083-6729(08)60359-3. [DOI] [PubMed] [Google Scholar]
  12. Hamfelt A. Enzymatic determination of pyridoxal phosphate in plasma by decarboxylation of L-tyrosine-14 C (U) and a comparison with the tryptophan load test. Scand J Clin Lab Invest. 1967;20(1):1–10. doi: 10.1080/00365516709076912. [DOI] [PubMed] [Google Scholar]
  13. Hamfelt A. Pyridoxal phosphate concentration and aminotransferase activity in human blood cells. Clin Chim Acta. 1967 Apr;16(1):19–28. doi: 10.1016/0009-8981(67)90264-1. [DOI] [PubMed] [Google Scholar]
  14. Hawkins R. D., Kalant H. The metabolism of ethanol and its metabolic effects. Pharmacol Rev. 1972 Mar;24(1):67–157. [PubMed] [Google Scholar]
  15. Hines J. D., Cowan D. H. Studies on the pathogenesis of alcohol-induced sideroblastic bone-marrow abnormalities. N Engl J Med. 1970 Aug 27;283(9):441–446. doi: 10.1056/NEJM197008272830901. [DOI] [PubMed] [Google Scholar]
  16. Hines J. D., Love D. S. Determination of serum and blood pyridoxal phosphate concentrations with purified rabbit skeletal muscle apophosphorylase b. J Lab Clin Med. 1969 Feb;73(2):343–349. [PubMed] [Google Scholar]
  17. Johansson S., Lindstedt S., Tiselius H. G. Metabolism of [3H8] pyridoxine in mice. Biochemistry. 1968 Jun;7(6):2327–2332. doi: 10.1021/bi00846a039. [DOI] [PubMed] [Google Scholar]
  18. KIESSLING K. H. The effect of acetaldehyde on rat brain mitochondria and its occurrence in brain after alcohol injection. Exp Cell Res. 1962 Mar;26:432–434. doi: 10.1016/0014-4827(62)90196-9. [DOI] [PubMed] [Google Scholar]
  19. LERNER A. M., DECARLI L. M., DAVIDSON C. S. Association of pyridoxine deficiency and convulsions in alcoholics. Proc Soc Exp Biol Med. 1958 Aug-Sep;98(4):841–843. doi: 10.3181/00379727-98-24203. [DOI] [PubMed] [Google Scholar]
  20. Lahti R. A., Majchrowicz E. Acetaldehyde--an inhibitor of the enzymatic oxidation of 5-hydroxyindoleacetaldehyde. Biochem Pharmacol. 1969 Feb;18(2):535–538. doi: 10.1016/0006-2952(69)90231-7. [DOI] [PubMed] [Google Scholar]
  21. Lahti R. A., Majchrowicz E. The effects of acetaldehyde on serotonin metabolism. Life Sci. 1967 Jul 1;6(13):1399–1406. doi: 10.1016/0024-3205(67)90187-7. [DOI] [PubMed] [Google Scholar]
  22. Majchrowicz E., Mendelson J. H. Blood concentrations of acetaldehyde and ethanol in chronic alcoholics. Science. 1970 May 29;168(3935):1100–1102. doi: 10.1126/science.168.3935.1100. [DOI] [PubMed] [Google Scholar]
  23. Okada M., Ochi A. The effect of dietary protein level on transaminase activities and fat deposition in vitamin B 6 -depleted rat liver. J Biochem. 1971 Oct;70(4):581–585. doi: 10.1093/oxfordjournals.jbchem.a129674. [DOI] [PubMed] [Google Scholar]
  24. Rose I. A., Warms J. V. Control of glycolysis in the human red blood cell. J Biol Chem. 1966 Nov 10;241(21):4848–4854. [PubMed] [Google Scholar]
  25. Sauberlich H. E., Canham J. E., Baker E. M., Raica N., Jr, Herman Y. F. Biochemical assessment of the nutritional status of vitamin B 6 in the human. Am J Clin Nutr. 1972 Jun;25(6):629–642. doi: 10.1093/ajcn/25.6.629. [DOI] [PubMed] [Google Scholar]
  26. Schreiber S. S., Briden K., Oratz M., Rothschild M. A. Ethanol, acetaldehyde, and myocardial protein synthesis. J Clin Invest. 1972 Nov;51(11):2820–2826. doi: 10.1172/JCI107104. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Srivastava S. K., Beutler E. The effect of normal red cell constituents on the activities of red cell enzymes. Arch Biochem Biophys. 1972 Jan;148(1):249–255. doi: 10.1016/0003-9861(72)90138-5. [DOI] [PubMed] [Google Scholar]
  28. TURNER J. M., HAPPOLD F. C. Pyridoxamine phosphate-oxidase and pyridoxal phosphate-phosphatase activities in Escherichia coli. Biochem J. 1961 Feb;78:364–372. doi: 10.1042/bj0780364. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. 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]
  30. White R. S., Dempsey W. B. Purification and properties of vitamin B6 kinase from Escherichia coli B. Biochemistry. 1970 Oct 13;9(21):4057–4064. doi: 10.1021/bi00823a005. [DOI] [PubMed] [Google Scholar]
  31. Yamada K., Tsuji M. Transport of vitamin B6 in human erythrocytes. J Vitaminol (Kyoto) 1968 Dec 10;14(4):282–294. doi: 10.5925/jnsv1954.14.282. [DOI] [PubMed] [Google Scholar]

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