-!- In some bacteria, a single protein catalyzes both this activity and that of EC 6.3.2.17, the combined activity of which leads to the formation of the coenzyme polyglutamated tetrahydropteroate (H(4)PteGlu(n)), i.e. various tetrahydrofolates. -!- In contrast, the activities are located on separate proteins in most eukaryotes studied to date. -!- This enzyme is reponsible for attaching the first glutamate residue to dihydropteroate to form dihydrofolate and is present only in those organisms that have the ability to synthesize tetrahydrofolate de novo, e.g. plants, most bacteria, fungi and protozoa.

-!- In some bacteria, a single protein catalyzes both this activity and that of EC 6.3.2.12, the combined activity of which leads to the formation of the coenzyme polyglutamated tetrahydropteroate (H(4)PteGlu(n)), i.e. various tetrahydrofolates (H(4)folate). -!- In contrast, the activities are located on separate proteins in most eukaryotes studied to date. -!- In Arabidopsis thaliana, this enzyme is present as distinct isoforms in the mitochondria, the cytosol and the chloroplast. -!- Each isoform is encoded by a separate gene, a situation that is unique among eukaryotes. -!- As the affinity of folate-dependent enzymes increases markedly with the number of glutamic residues, the tetrahydropteroyl polyglutamates are the preferred coenzymes of C(1) metabolism. -!- The enzymes from different sources (particularly eukaryotes versus prokaryotes) have different substrate specificities with regard to one-carbon substituents and the number of glutamate residues present on the tetrahydrofolates.