Relationship between vitamin B-6 status and elevated pyridoxal kinase levels induced by theophylline therapy in humans.
Theophylline administration to seven healthy male volunteers resulted in a rapid and significant decline in both plasma and erythrocyte pyridoxal-5'-phosphate levels. Total erythrocyte pyridoxal kinase levels increased during 15 wk of theophylline treatment from a mean initial activity of 19.23 +/- 5.03 (mean +/- SD) to 62.64 +/- 11.59 nmol pyridoxal-5'-phosphate formed/(g hemoglobin.h). Although plasma pyridoxal levels remained normal, the threefold increase in total erythrocyte pyridoxal kinase activity levels did not normalize plasma and erythrocyte pyridoxal-5'-phosphate levels. Pyridoxal-5'-phosphate hydrolysis was not affected by theophylline therapy. Increased pyridoxal oxidation was confirmed by elevated urinary 4-pyridoxic acid excretion after 15 wk of theophylline treatment. Mean erythrocyte alanine aminotransferase activity declined by 70%, and aspartate aminotransferase activity declined by 50%, indicating that decreased availability of pyridoxal-5'-phosphate can have widespread metabolic consequences. We conclude that the effect of theophylline on vitamin B-6 metabolism is not transitory and cannot be overcome by elevated intracellular levels of pyridoxal kinase. However, pyridoxine supplementation (10 mg/d for 1 wk) normalized indices of vitamin B-6 status and reversed the downward trend in both alanine aminotransferase and aspartate aminotransferase activity levels.
Ubbink
J B
JB
Department of Chemical Pathology, University of Pretoria, South Africa.
Delport
R
R
Bissbort
S
S
Vermaak
W J
WJ
Becker
P J
PJ
D000328:Adult; D006706:Homeostasis; D006801:Humans; D008297:Male; D009752:Nutritional Status; D011731:Pyridoxal Kinase / Q000097:blood / Q000378:metabolism*; D011732:Pyridoxal Phosphate / Q000097:blood*; D011736:Pyridoxine / Q000378:metabolism*; D013806:Theophylline / Q000097:blood / Q000627:therapeutic use*
D011732:Pyridoxal Phosphate; D013806:Theophylline; D011731:Pyridoxal Kinase; D011736:Pyridoxine