Formiminoglutamic acid-

B37. Brown, D. D., Silva, O. L., Gardiner, R. C., and Silverman, M., Metabolism of formiminoglutamic acid by vitamin B12 and folic acid deficient rats fed excess methionine. J. Biol. Chem. 235, 2058-2062 (1960). 

K7. Kohn, J., Mollin, D. L., and Rosenbach, L. M., Conventional voltage electrophoresis for formiminoglutamic acid determination and folic acid deficiency. /. Clin. Pathol. 14, 345-350 (1961). 

Chanarin, L, Rothman, D and Watson-Williams, E, J, (1963). Normal formiminoglutamic acid excretion in megaloblastic anemia In pregnancy. Lancet 1,1068-1072. 

The histidine load test is not used in the clinical setting and is only sometimes used by researchers however, a description of this test provides a clear-cut example of how folates behave in the mediation of 1-carbon metabolism. Histidine catabolism takes place in the liver according to the pathway shown (Figures 9.16 and 9.17). The intermediates, formiminoglutamic acid and 5-formimino-H4folate, bear the formimino group —CH=NH. 

Connecting peptide of insulin Cytosine triphosphate Extracellular fluid Essential fatty acid Endoplasmic reticulum Fructose-l,6-bisphosphate Flavin adenine dinucleotide Free fatty acid Formiminoglutamic acid Glucose transporter gene or protein... 

Folic acid also has an important role in histidine catabolism (Fig. 4), where the formimino group of the end-stage product formiminoglutamic acid is transferred to tetrahydrofolate, giving formiminotetrahydrofolate. 

With the introduction in 1960 (B6) of an improved and sensitive microbiological assay for folate the measurement of formiminoglutamic acid was no longer used as a diagnostic test, although it continues to be used as a research tool. The microbiological assay has in turn now been replaced in many laboratories by isotope dilution techniques. 

The pathway in the catabolism of L-histidine is to urocanic acid, 4-im-idazolene-5-propionic acid, and formiminoglutamic acid. The formimino... 

In 1962, a physician (H14) placed himself on a diet which, when assayed, was found to provide only 5 pg of folate daily. Up to that time no diet had been devised that contained so little folate, and it was made possible only by boiling each 100 g portion of all those constituents that contained more than a trace of the vitamin for 10 minutes in two liters of water. Tlie water was then discarded and the procedure repeated twice (H15). On this diet early megaloblastic change was noted after 137 days. The serum level of the vitamin fell after 14 days followed by the appearance of hypersegmented neutrophils. Formiminoglutamic acid then appeared in the urine and shortly before the megaloblastic change occurred the red cell folate fell. This experiment provided important information on body stores and the sequence of events in folate deficiency. While the diet was not completely free of folate, its content had been carefully measured and was very small. It was calcu-... 

Formiminotransferase deBciency syndrome was first described in two patients by Arakawa (A7). It was characterized by mental retardation, a very high serum folate level, and excessive excretion of formiminoglutamic acid following a histidine load. A third patient with this syndrome was later... 

Another variant has been found affecting two sisters (N5, N6). This was characterized by the urinary excretion of large quantities of hydantoin-5-propionic acid and formiminoglutamic acid, and was unresponsive to treatment with folic acid. One had retarded speech, but this was the only defect, and the other child was normal. 

There have been other single reports of megaloblastic anemia associated with an apparent abnormality of folate metabolism. One child had a normal serum folate of 6 p,g/liter, an erythrocyte folate of 1480 p.g/liter, and a megaloblastic anemia which responded to treatment with folic acid (VI). Lampkin (Lll) described two sisters with a severe megaloblastic anemia and normal vitamin 6 2 folate levels. Absorption of vitamin 6, 2 normal and both patients excreted an increased amount of formiminoglutamic acid. It was thought that they required both vitamin B 2 and folate to restore normoblastic hemopoiesis. 

K2. Knowles, J. P., Prankerd, T. A. J., and Westall, R. C., Simplified method for detecting formiminoglutamic acid in urine as a test of folic-acid deficiency. Lancet 2, 347-348 (1960). 

FIGURE 53-6 Interrelationships and metabolic roles of vitamin and folic acid. See text for explanation and Figure 53-9 for structures of the various folate coenzymes. FIGLU, formiminoglutamic acid, which arises from die catabolism of histidine Tell, transcobalamin II CH3H4PteGlUj, mediyltetrahydrofolate. 

Histidine metabolism. H PteGlu also acts as an acceptor of aformimino group in the conversion of formiminoglutamic acid to glutamic acid. 

Applegarth D A and Poon S (1975a) Determination of formiminoglutamic acid by lon-exchange chromatography Lancet I, 1346. 

Tetrahydrofolic acid is also an enzymic acceptor of a formimino group from formiminoglycine or from formiminoglutamic acid. The product, 5-formimino-5,6,7,8-tetrahydrofolic acid, is converted in acidic solution to anhydrofolinic acid and ammonium ion and has a half-Ufe of about i h at 37° over a pH range i of 5-9. Aerobic oxidation of tetrahydrofolic acid produces />-aminobenzoy lutamic acid and a number of pteridines, including xanthopterin . ... 

Urocanic acid is degraded by urocanase. Although this enzyme has been purified from both animal and bacterial sources,its mode of action remains obscure. The first product to accumulate is the open-chain formiminoglutamic acid. There is no evidence for more than one enzyme participating in this reaction which involves the addition of two water molecules and opening the imidazole ring (IV). No dissociable cofactor has been detected. The enzyme that removes the 277 mp absorption has a pH optimum near 7. 

The metabolism of formiminoglutamic acid varies in different organisms. In Psevdomonas extracts, formiminoglutamic acid is converted to formylglutamic acid and ammonia by an enzyme that has not been purified, but is active in the presence of sulfhydryl compounds that inhibit... 

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