Poly-y-glutamylation of Folate

Folate polyglutamate synthetase binds ATP, tetrahydrofolate-(oligo)-glutamate, then glutamate sequentially forming an intermediate folate 

The principal substrate for glutamylation is free tetrahydrofolate one-carbon substituted folates tne poor substrates. Because the main circulating folate, and the main form that is taken up into tissues, is methyl-tetrahydrofolate, demethylation by the action of methionine synthetase (Section 10.3.3) is essential for effective metabolic trapping of folate. In vitamin B12 deficiency, when methionine synthetase activity is impaired, there will be impairment of the retention of folate in tissues. 

Under normal conditions, the predominant folates in liver are pentaglu-tamates, with small amounts of tetra- and hexaglutamates. The extent of poly-glutamylation is controlled to a great extent by the avcdlabiUty of folate in deficient animals, hexa- to octaglutcunates predominate, whereas in supplemented tmimtils, liver folate is msdnly as the tri- to pentciglutcunates (Cassady etal., 1980). 

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