Activation and protection from 5-fluorodeoxyuridylate inactivation of mammalian thymidylate synthetase by pyridoxal 5'-phosphate.

Rat liver thymidylate synthetase was partially purified by a combination of (NH4)2SO4 precipitation and Sephadex chromatography. Incubation of these partially purified enzyme preparations with pyridoxal phosphate resulted in as much as a 12-fold increase in enzyme activity. In addition, incubation of partially purified thymidylate synthetase preparations with 5.0 X 10(-5) M pyridoxal phosphate protected the enzyme from 5-fluorodeoxyuridylate inhibition to the extent that 78% of the control activity was retained at 5-fluorodeoxyuridylate concentrations as high as 5.0 X 10(-5) M. These findings are discussed in terms of the reported inhibition of tumour growth in the absence of dietary vitamin B6.