Red cell aspartate aminotransferase saturation with oral pyridoxine intake
Keywords:
Pyridoxine, Pyridoxal phosphate, Aspartate aminotransferase, Sideroblastic anemia, Myelofi brosisAbstract
CONTEXT AND OBJECTIVE: The coenzyme of aspartate aminotransferase is pyridoxal phosphate, generated from fresh vegetables containing pyridoxine. Vitamin B6-responsive sideroblastic anemia, myelofibrosis and Peyronie’s syndrome respond to high pyridoxine doses. The objective was to investigate the oral pyridoxine oral dose that would lead to maximized pyridoxal phosphate saturation of red cell aspartate aminotransferase. DESIGN AND SETTING: Controlled trial, in Hematology Division of Instituto Adolfo Lutz. METHODS: Red cell aspartate aminotransfe- rase activity was assayed (before and after) in normal volunteers who were given oral pyridoxine for 15-18 days (30 mg, 100 mg and 200 mg daily). In vitro study of blood from seven normal volunteers was also performed, with before and after assaying of aspartate aminotransferase activity. RESULTS: The in vivo study showed increasing aspartate aminotransferase saturation with increasing pyridoxine doses. 83% saturation was reached with 30 mg daily, 88% with 100 mg, and 93% with 200 mg after 20 days of oral supplementation. The in vitro study did not reach 100% saturation. CONCLUSIONS: Neither in vivo nor in vitro study demonstrated thorough aspartate aminotransferase saturation with its coenzyme pyridoxal phosphate in red cells, from increasing pyridoxine supplementation. However, the 200-mg dose could be employed safely in vitamin B6- responsive sideroblastic anemia, myelofibrosis and Peyronie’s syndrome treatment. Although maximum saturation in circulating red cells is not achieved, erythroblasts and other nucleated and cytoplasmic organelles containing cells certainly will reach thorough saturation, which possibly explains the results obtained in these diseases.
Downloads
References
Anderson BB, Fulford-Jones CE, Child JA, Beard ME, Bateman CJ. Conversion of vitamin B6 compounds to active forms in the red blood cell. J Clin Invest. 1971;50(9):1901-9.
Delport R, Ubbink JB, Vermaak WJ, Shaw A, Bissbort S, Becker PJ. Relationship between maternal and neonatal vitamin B6 metabolism: perspectives from enzyme studies. Nutrition. 1991;7(4):260-4; discussion 264-6.
Hathcock JN. Vitamins and minerals: efficacy and safety. Am J Clin Nutr. 1997;66(2):427-37.
Olszewer E. Vitaminas. In: Olszewer E (ed.). ABC da Medicina Ortomolecular. São Paulo: Tecnopress; 1997. p. 12-3.
Rojer RA, Mulder NH, Nieweg HO. Response to pyridoxine hydrochloride in refractory anemia due to myelofibrosis. Am J Med. 1978;65(4):655-60.
Bitsch R. Vitamin B6. Int J Vitam Nutr Res. 1993;63(4):278-82.
Leklem JE. Vitamin B6. In: Shilds ME, Olson JA, Shike M, editors. Modern nutrition in health in disease. Philadelphia: Lea & Febiger; 1994. p. 383-94.
Sauberlich HE, Canham JE, Baker EM, Raica N, Herman YF. Biochemical assessment of the nutritional status of vitamin B6 in the human. Am J Clin Nutr. 1972;25(6):629-42.
Vudhivai N, Pongpaew P, Prayurahong B, et al. Vitamin B1, B2, and B6 in relation to anthropometry, hemoglobin and albumin of newborns and their mothers from northeast Thailand. Int J Vitam Nutr Res. 1990;60(1):75-80.
Solomon LR, Hillman RS. Vitamin B6 metabolism in hu- man red cells. I. Variations in normal subjects. Enzyme. 1978;23(4):262-73.
Beutler E. Red cell metabolism – A manual of biochemical methods. 3rd ed. Orlando: Grune & Stratton; 1984.
Ames BN, Elson-Schwab I, Silver EA. High-dose vitamin therapy stimulates variant enzymes with decreased coenzyme binding affinity (increased K(m)): relevance to genetic disease and polymorphisms. Am J Clin Nutr 2002;75(4):616-58.
Bender DA. Novel functions of vitamin B6. Proc Nutr Soc. 1994;53(3):625-30.
Rucker RB, Stites T. New perspectives on function of vitamins. Nutrition. 1994;10(6):507-13.
Garret RH, Grisham CM. Coenzymes and vitamins. In: Voet D, Voet JG, editors. Biochemistry. Florida: Saunders College Publishing; 1995. p. 474-80.
Award Jr. WM. Iron and heme metabolism. In: Devlin TM, editor. Textbook of Biochemistry with clinical correlations. New York: Wiley-Liss; 1997. p.1001-24.
Bull BS, Breton-Gorius J. Morphology of the erythron. In: Beutler E, Lichtman MA, Coller BS, Kipps TJ, editors. Williams Hematology. 5th ed. New York: McGraw-Hill; 1995. p.354-63.
Rose DP, Strong R, Folkard J, Adams PW. Erythrocyte aminotrans- ferase activities in women using oral contraceptives and the effect of vitamin B6 supplementation. Am J Clin Nutr. 1973;26(1):48-52.
Fonda ML. Purification and characterization of vitamin B6- phosphate phosphatase from human erythrocytes. J Biol Chem. 1992;267(22):15978-83.
Fischer I, Walter H. Aspartate aminotransferase (GOT) from young and old human erythrocytes. J Lab Clin Med. 1971;78(5):736-45.
Solomon LR. Considerations in the use of B6 vitamers in hematologic disorders: I. Red cell transport and metabolism of pyridoxal. Blood. 1982;59(3):495-501.
