Pteroylpolyglutamates

Abstract

Reduced derivatives of the vitamin pteroylglutamic acid (folic acid) are essential coenzymes for the biosynthesis of purine nucleotides, methionine, thymidylate and for many other enzyme catalyzed reactions involving the transfer, oxidation and reduction of single carbon units. Pteroylglutamic acid is found in tissues in the form of poly-gamma-glutamyl derivatives of varying chain length. The present review covers the detection, distribution, synthesis, degradation, coenzyme function and inhibitory activities of pteroyl-gamma-glutamates. The biosynthesis and inhibitory activities of poly-gamma-glutamyl derivatives of methotrexate, an analog of pteroylglutamic acid having antitumor activity, are also considered. An hypothesis on the coenzymatic role of pteroylpoly-gamma-glutamates in the coordination of sequential enzymatic steps in the metabolism of single carbon units is presented.