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Cytosolic folylpolyglutamate synthase catalyzes the reaction of THF-glutamate(n), L-glutamate, and ATP to form THF-glutamate(n+1), ADP, and orthophosphate. (The first glutamate residue is attached to the glutamate moiety of THF itself; for convenience the process is annotated here as if it proceeded in a single concerted step.) The extent of conjugation is variable, but the commonest cytosolic form of THF has five added glutamate residues. Although its properties as a donor of one-carbon units are not affected by glutamate addition, THF that lacks added glutamate residues cannot be retained in the cytosol so this reaction is needed for normal THF function under physiological conditions (Garrow et al. 1992; Chen et al. 1996).
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