Fig. 1. Chemical structures of tetrahydrofolate and its C1-substituted derivatives. Natural folates occur mainly as polyglutamylated forms in which a -linked chain of up to about eight residues is added to the glutamate moiety. Numbered arrowheads mark potential sites of action of catabolic enzymes (see text). The removal of the polyglutamyl tail after the first glutamate (reaction 4, mentioned in the text) is not shown on this figure.