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.
D000818:Animals; D003856:Deoxyuracil Nucleotides / Q000494:pharmacology*; D004789:Enzyme Activation; D005260:Female; D005468:Fluorodeoxyuridylate / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology*; D008780:Methyltransferases / Q000378:metabolism*; D011732:Pyridoxal Phosphate / Q000494:pharmacology*; D051381:Rats; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*
D003856:Deoxyuracil Nucleotides; D005468:Fluorodeoxyuridylate; D011732:Pyridoxal Phosphate; D008780:Methyltransferases; D013940:Thymidylate Synthase