Inhibition of pyridoxal kinase by methylxanthines.
In the presence of saturating concentrations of adenosine triphosphate (ATP) and rate-limiting amounts of pyridoxal, theophylline was found to inhibit sheep brain pyridoxal kinase (EC 2.7.1.35) competitively. The apparent inhibition constant (Ki) of theophylline for pyridoxal kinase was determined as 8.7 mumol/l. Theophylline concentrations of up to 60 mumol/l did not affect pyridoxal phosphorylation in the presence of saturating amounts of pyridoxal and rate-limiting concentrations of ATP. Caffeine was less potent to inhibit pyridoxal kinase (Ki = 45 mumol/l) due to the presence of a methyl group on the 7 position of the xanthine ring structure. Theobromine showed only a weak inhibition of pyridoxal kinase (Ki = 453 mumol/l). The presence of a hydroxyethyl, hydroxypropyl or dihydroxypropyl group on the N7 position of theophylline completely abolished inhibition of pyridoxal kinase. Enprofylline (3-propylxanthine), a recently described bronchodilator, was also able to inhibit pyridoxal kinase with a Ki of 256 mumol/l.[1]References
- Inhibition of pyridoxal kinase by methylxanthines. Ubbink, J.B., Bissbort, S., Vermaak, W.J., Delport, R. Enzyme (1990) [Pubmed]
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