Formimino glutamic acid

B36. Broquist, H. P., and Luhby, A. L., Detection and isolation of formimino-glutamic acid from urine in folic acid deficiency in humans. Proc. Soc. Exptl. Biol. Med. 100, 349-354 (1959). 

H7. Hiatt, H. H., Goldstein, M., and Tabor, H., Urinary excretion of formimino-glutamic acid by human subjects after antifolic acid therapy. J. Clin. Invest. 37, 829-832 (1958). 

Fig. 11.6. Interconversions of tetrahydrofolate derivatives. FH2 = dihydrofolic acid FH4 = tetrahydrofolic acid AICAR -= 5 aminoimidazole 4-carboxamide ribonucleotide FAICAR = formyl AICAR GAR = glycinamide ribonucleotide FGAR = formyl GAR Glu = glutamic acid FIGLU = formimino glutamic acid. (Modified from Mudd and Cantoni, 1964.)...

The evidence that the product of the urocanase reaction is 4(6)-imidazolone-5(4)-propionic acid is based primarily on the rimilarity of its spectral characteristics in acid, alkaline, and neutral solutions to synthetic 4(5)-imidazoline and 4(5)-imidazolone-5(4)-acetic acid, which have been prepared by Witkop and co-workers 262, 263). These compounds are degraded by bacterial enzyme extracts to formiminoglycine and formi-minoaspartic acid in a manner rimilar to the formation of formimino-glutamic acid in the reaction with crude urocanase preparations. 

When a crude liver extract is added to the purified urocanase, decomposition of urocanic acid proceeds to W-formimino-L-glutamic acid. The enzyme carrying out this stage of the reaction has been named imidazolonepropionic acid hydrolase. In view of the fact that im-idazolonepropionic acid has not been isolated and study of the hydrolysis reaction can only be performed in incubation mixtures in which urocanic acid is reacted with purified urocanase very little is known about the properties of the hydrolase enzyme. This enzyme has been purified about tenfold by ammonium sulfate fractionation in our laboratory (266). The enzyme activity is shown by an acceleration in the rate of the decomposition of the 264 my absorption. The product formed was shown to be formimino glutamic acid by testing with purified formiminotransferase which is specific for this compound. 

Histidine ammonia-lyase 2 urocanate hydratase 3 imidazolone propionase 4 glutamate form-iminotransferase (the enzyme occurs in vertebrates and forms 5-formimino tetrahydrofolic acid)... 

Dilute enzyme solutions of the above microorganisms convert urocanic acid to iV-formimino-L-glutamic acid as do also liver enzyme preparations. 

This compound, it was discovered, was excreted in the urine of rodents maintained on a folic acid-deficient diet 251). The amount excreted was increased on feeding histidine. Furthermore, it was shown that histidine was the precursor of the formiminoglutamic acid by the administration of histidine-N . The glutamic acid derived from the isolated formimino-glutamate contained the calculated quantity of the label. 

This enzyme converts formiminoglutamic acid to glutamic acid 266, 267). The formimino group is transferred to form 5-formiminotetra-hydrofolic acid. This in turn is transformed by two other enzymes, first to yield 6,10-methenyl-FH4 and NHs, and subsequently 10-formyl-FH4 (FH4 for tetrahydrofolic acid). 

Another active folic acid compound was formed during the conversion of serine to glycine. This compound, a hydroxymethyl derivative of FH , was enzymically oxidized to iV ,JVi -anhydroformyl-FH4 (108, IIS). The anhydro derivative was also produced in the catabolism of formiminoglycine (114, 115) and formiminoglutamic acid (114) via AT -formimino-FH4. An active formyl-FH4 derivative, presumably JVi -formyl-FH4, also arose when IMP and FH4 reacted to produce AICAR (108) (see Section II, B, 5). iV -Formyl-FH4 reacted with glutamic acid to form iV-formyl utamic acid... 

FIQLU + 6-CHNH—FH. -1-glutamic acid Formimino transferase (from liver) (41,58)... 

FIGURE 18-26 Catabolic pathways for arginine, histidine, glutamate, glutamine, and proline. These amino acids are converted to a-ketoglutarate. The numbered steps in the histidine pathway are catalyzed by histidine ammonia lyase, urocanate hydratase, imida-zolonepropionase, and glutamate formimino transferase. 

Tetrahydrofolic acid Folic acid (B9) Glutamate Methyl, formyl, residues methylene and formimino groups Bacteria, archaea and eukaryotes... 

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