Folylpolyglutamates

Shane B Folylpolyglutamate synthesis and role In the regulation of one-carbon metabolism. Vitam Horm 1989 45 263. 

Determination of folylpolyglutamate hydrolase activity PXS 10/25 ODS Aq. 0.20M NaLS HPLC 224... 

Brody, T and Stokstad, E. 1,. R. (1991). Incorpofotion of the 2-ring carbon of histidine into folylpolyglutamate coeniymes, /, Nwtr, BiocHeta. Z, 492-498. 

The data in Table 9.1 are from an experiment involving folylpolyglutamate synthase. The enzyme was obtained in purified form from liver and was mixed with glutamic acid, ATP, and the indicated form of folate. The mixture was incubated to permit the enzyme to catalyze the attachment of glutamate residues to the folate. What do you think would be the effect of a vitamin B12 deficiency on the rate of polyglutamation of dietary folates. Hint Dietary folates occur in the bloodstream initially as 5-methyl-H4PteGlu, and enter the cell in this form. 

Longo GS, Gorlick R, TongWP, Lin S, Steinherz P, Bertino IR (1997) Glutamyl hydrolase and folylpolyglutamate synthetase activities predict polyglutamylation of methotrexate in acute leukemias. Oncol Res 9 259-263... 

Barredo JC, Synold TW, Laver J, Relling MV, Pui CH, Priest DG et al (1994) Differences in constitutive and post-methotrexate folylpolyglutamate synthetase activity in B-lineage and T-lineage leukemia. Blood 84 564-569... 

Rots MG, Pieters R, Peters GI, Noordhuis P, van Zantwijk CH, Kaspers GI et al (1999) Role of folylpolyglutamate synthetase and folylpolyglutamate hydrolase in methotrexate accumulation and polyglutamylation in childhood leukemia. Blood 93 1677-1683... 

Ferone, R Singer, S.C., and Hunt, D.F. (1986) In vitro synthesis of a-carboxyl-linked folylpolyglutamates by an enzyme preparation from Escherichia coli.J. Biol. Chem., 261 (35), 16363-16371. 

Salcedo, E., Cortese, J. F., Plowe, C. V., Sims, P. F., and Hyde, J. E. (2001). A bifunctional dihydrofolate synthetase-folylpolyglutamate synthetase in Plasmodium falciparum identified by functional complementation in yeast and bacteria. Mol. Biochem. Parasitol. 112, 239-252. 

Figure 2 Biosynthesis of foiates. a, GTP cyclohydrolase I b, dihydroneopterin epimerase c, nudix hydrolase d, phosphatase e, dihydroneopterin aldolase f, hydroxymethyidihydropterin pyrophosphokinase g, dihydropteroate synthase h, dihydrofolate synthetase I, dihydrofolate reductase j, folylpolyglutamate synthetase k, aminodeoxychorismate synthase I, aminodeoxychorismate lyase. 7, 7,8-dihydro-D-neopterin 3 -triphosphate 8, 7,8-dihydro-L-monapterin 3 -triphosphate 9, 7,8-dihydro-D-neopterin 3 -monophosphate 10, 7,8-dihydro-D-neopterin 11, glycolaldehyde ...

Certain bacteria including E. coli form bifunctional enzymes with dihydrofolate and folylpolyglutamate synthetase (Figure 2, j) activityBoth the conversion of dihydropteroate into dihydrofolate and the subsequent attachment of additional glutamate moieties by the bifunctional E. coli enzyme have been shown to involve the transient formation of acyl phosphate intermediates. ... 

The three-dimensional structure of folylpolyglutamate synthase of Lactobacillus casei and E. coli have been determined by X-ray crystallography. The catalytically active conformation of the protein is obtained by bonding of a folate-type substrate binding of ATP is not, perse, sufficient to generate that conformational state. 

Folylpolyglutamate synthetases, including the bifunctional FolC proteins of bacterial origin, are members of a superfamily including the Mur proteins involved in bacterial cell wall biosynthesis. ... 

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