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. 1975 May;55(5):1026–1032. doi: 10.1172/JCI108003

Vitamin B6 metabolism in chronic alcohol abuse The effect of ethanol oxidation on hepatic pyridoxal 5'-phosphate metabolism.

R L Vech, L Lumeng, T K Li
PMCID: PMC301849  PMID: 1168205

Abstract

Individuals with chronic alcohol abuse frequently exhibit lowered plasma levels of pyridoxal 5'-phosphate, the coenzyme form of vitamin B6. Because the liver is the primary source of this coenzyme in plasma and also the principal organ that oxidizes ethanol, the effect of ethanol on hepatic pyridoxal phosphate metabolism was studied in the rat. The chronic feeding of ethanol (36 percent of the total dietary calories) for 6 wk significantly decreased the hepatic pyridoxal phosphate content both in animals given a sufficient amount of vitamin B6 in their diet and in those rendered vitamin B6 deficient. In isolated perfused livers, the addition of 18 mM ethanol lowered the pyridoxal phosphate content of livers from vitamin B6-sufficient animals and deceased the net synthesis of pyridoxal phosphate from pyridoxine by the livers of vitamin B6-deficient animals. Ethanol also diminished the rate of release of pyridoxal phosphate into the perfusate by the livers of vitamin B6-deficient rats. These effects of ethanol, in vitro, were abolished by 4-methyl pyrazole, an inhibitor of alcohol dehydrogenase. Thus the derangement of pyridoxal phosphate metabolism produced by ethanol is dependt upon its oxidation. These data support previous findings whic indicate that acetaldehyde is the responsible agent which acts by accelerating the degradation of intracellular pyridoxal phosphate.

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Selected References

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  1. 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]
  2. Beaton G. H., Cheney M. C. Vitamin B6 requirement of the male albino rat. J Nutr. 1965 Sep;87(1):125–132. doi: 10.1093/jn/87.1.125. [DOI] [PubMed] [Google Scholar]
  3. Blomstrand R., Theorell H. Inhibitory effect on ethanol oxidation in man after administration of 4-methylpyrazole. Life Sci II. 1970 Jun 8;9(11):631–640. doi: 10.1016/0024-3205(70)90214-6. [DOI] [PubMed] [Google Scholar]
  4. Brin M., Thiele V. F. Relationships between vitamin B6-vitamer content and the activities of two transaminase enzymes in rat tissues at varying intake levels of vitamin B6. J Nutr. 1967 Oct;93(2):213–221. doi: 10.1093/jn/93.2.213. [DOI] [PubMed] [Google Scholar]
  5. Chatagner F. Influences of pyridoxine derivatives on the biosynthesis and stability of pyridoxal phosphate enzymes. Vitam Horm. 1970;28:291–302. doi: 10.1016/s0083-6729(08)60898-5. [DOI] [PubMed] [Google Scholar]
  6. Churchich J. E. Cofactor transfer from cystathionase to aspartate aminotransferase. Biochem Biophys Res Commun. 1970 Sep 30;40(6):1374–1379. doi: 10.1016/0006-291x(70)90018-5. [DOI] [PubMed] [Google Scholar]
  7. Driskell J. A., Strickland L. A., Poon C. H., Foshee D. P. The vitamin B 6 requirement of the male rat as determined by behavioral patterns, brain pyridoxal phosphate and nucleic acid composition and erythrocyte alanine aminotransferase activity. J Nutr. 1973 May;103(5):670–680. doi: 10.1093/jn/103.5.670. [DOI] [PubMed] [Google Scholar]
  8. Driskell J. A., Wiley J. H., Kirksey A. Alanine aminotransferase activity in liver and erythrocytes of pregnant and nonpregnant rats fed different levels of pyridoxine. J Nutr. 1971 Jan;101(1):85–91. doi: 10.1093/jn/101.1.85. [DOI] [PubMed] [Google Scholar]
  9. 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]
  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. Hems R., Ross B. D., Berry M. N., Krebs H. A. Gluconeogenesis in the perfused rat liver. Biochem J. 1966 Nov;101(2):284–292. doi: 10.1042/bj1010284. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. 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]
  13. Jones D., Gerber L. P., Drell W. A rapid enzymatic method for estimating ethanol in body fluids. Clin Chem. 1970 May;16(5):402–407. [PubMed] [Google Scholar]
  14. Jukes T. H. Are recommended daily allowances for vitamin C adequate? Proc Natl Acad Sci U S A. 1974 May;71(5):1949–1951. doi: 10.1073/pnas.71.5.1949. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Krebs H. A., Freedland R. A., Hems R., Stubbs M. Inhibition of hepatic gluconeogenesis by ethanol. Biochem J. 1969 Mar;112(1):117–124. doi: 10.1042/bj1120117. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  17. Li T. K., Lumeng L., Veitch R. L. Regulation of pyridoxal 5'-phosphate metabolism in liver. Biochem Biophys Res Commun. 1974 Nov 27;61(2):677–684. doi: 10.1016/0006-291x(74)91010-9. [DOI] [PubMed] [Google Scholar]
  18. Li T. K., Theorell H. Human liver alcohol dehydrogenase: inhibition by pyrazole and pyrazole analogs. Acta Chem Scand. 1969;23(3):892–902. doi: 10.3891/acta.chem.scand.23-0892. [DOI] [PubMed] [Google Scholar]
  19. Lieber C. S., DeCarli L. M. Quantitative relationship between amount of dietary fat and severity of alcoholic fatty liver. Am J Clin Nutr. 1970 Apr;23(4):474–478. doi: 10.1093/ajcn/23.4.474. [DOI] [PubMed] [Google Scholar]
  20. Lumeng L., Brashear R. E., Li T. K. Pyridoxal 5'-phosphate in plasma: source, protein-binding, and cellular transport. J Lab Clin Med. 1974 Sep;84(3):334–343. [PubMed] [Google Scholar]
  21. Lumeng L., Li T. K. 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. J Clin Invest. 1974 Mar;53(3):693–704. doi: 10.1172/JCI107607. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. MILLER L. L., BLY C. G., WATSON M. L., BALE W. F. The dominant role of the liver in plasma protein synthesis; a direct study of the isolated perfused rat liver with the aid of lysine-epsilon-C14. J Exp Med. 1951 Nov;94(5):431–453. doi: 10.1084/jem.94.5.431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. RAABO E., TERKILDSEN T. C. On the enzymatic determination of blood glucose. Scand J Clin Lab Invest. 1960;12(4):402–407. doi: 10.3109/00365516009065404. [DOI] [PubMed] [Google Scholar]
  24. Sorrell M. F., Baker H., Barak A. J., Frank O. Release by ethanol of vitamins into rat liver perfusates. Am J Clin Nutr. 1974 Jul;27(7):743–745. doi: 10.1093/ajcn/27.7.743. [DOI] [PubMed] [Google Scholar]
  25. Takami M., Fujioka M., Wada H., Taguchi T. Studies on pyridoxine deficiency in rats. Proc Soc Exp Biol Med. 1968 Oct;129(1):110–117. doi: 10.3181/00379727-129-33263. [DOI] [PubMed] [Google Scholar]
  26. Theorell H., Chance B., Yonetani T., Oshino N. The combustion of alcohol and its inhibition by 4-methyl-pyrazole in perfused rat livers. Arch Biochem Biophys. 1972 Aug;151(2):434–444. doi: 10.1016/0003-9861(72)90519-x. [DOI] [PubMed] [Google Scholar]
  27. WIZGIRD J. P., GREENBERG L. D., MOON H. D. HEPATIC LESIONS IN PYRIDOXINE-DEFICIENT MONKEYS. Arch Pathol. 1965 Mar;79:317–323. [PubMed] [Google Scholar]
  28. Williamson J. R., Garcia A., Renold A. E., Cahill G. F., Jr Studies on the perfused rat liver. I. Effects of glucagon and insulin on glucose metabolism. Diabetes. 1966 Mar;15(3):183–187. doi: 10.2337/diab.15.3.183. [DOI] [PubMed] [Google Scholar]

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