Figure 1.

Schematic representation of the reactions catalyzed by (a) dihydrofolate synthetase (DHFS) and (b) folylpolyglutamate synthetase (FPGS). In both reactions the dihydropteroate or folate substrates have the same co-substrates (ATP and l-glutamate) and the reaction mechanisms are identical, involving (1) activation of the free carboxylate by ATP and (2) nucleophilic attack on the resulting acyl-phosphate intermediate by l-­glutamate. The different forms of the one-carbon derivatives of tetrahydrofolate are shown on the lower molecule: (i) 10-methyl, (ii) 5,10-methylene and (iii) 10-formyl.