ABSTRACT

Practically all tissue folates are polyglutamate forms in which the glutamate tail is extended through an unusual peptide bond via the gamma-carboxyl of glutamate. Glutamate chain lengths can vary from about 4 to 10 in human tissues. Metabolism of folates to polyglutamate forms is required for their biological activity, as the polyglutamate forms are much more effective substrates for folate-dependent enzymes than are the monoglutamate derivatives, which are the transport forms of the vitamin.[1] Conversion of folates to polyglutamates of chain length greater than 3 is also required for effective retention of folate by tissues.[2]

BIOCHEMISTRY AND FUNCTIONS

Folate coenzymes are involved in three major interrelated metabolic cycles in the cytosol of cells. These cycles are required for the synthesis of thymidylate and purines, precursors for DNA and RNA synthesis, and for the synthesis of methionine from homocysteine and the interconversion of serine and glycine (Fig. 2).