COMPETITIVE INHIBITION BETWEEN 4-SUBSTITUTED PYRIDOXINE ANALOGUES AND PYRIDOXNL FOR PYRIDOXAL KINASE FROM MOUSE BRAIN

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4-Substituted pyridoxine analogues (4-PN analogues), which were potent antagonists of vitamin B6, induced severe convulsions in mouse which could be prevented by vitamin B6. To elucidate the mechanism of the convulsive action, the effect of 4-PN analogues on partially purified pyridoxal kinase (PL-kinase) from mouse brain was studied. 4-Methoxypyridoxine (4-MPN), 4-ethoxypyridoxine (4-EPN), 4-propoxypyridoxine (4-PPN) and 4-isopropoxypyridoxine (4-iso PPN) were found to be powerful inhibitors of PL-kinase and competed with pyridoxal (PL). There was a good relationship between mouse convulsions and inhibitory activities of PL-kinase. We also studied whether 4-MPN, 4-EPN, 4-PPN and 4-isoPPN were used as substrates of PL-kinase. High-performance liquid chromatography was used to separate 4-PN 5-phosphate analogues and ADP which were formed in the enzyme reaction, and to measure them quantitatively. The results showed that 4-MPN, 4-EPN, 4-PPN and 4-isoPPN were also phosphorylated by PL-kinase like 4-deoxypyridoxine.
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