Formiminoglutamic acid, excretion

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

Thenen, S. W. (1978) Blood and liver folacin activity, formiminoglutamic acid excretion, growth and hematology in guinea pigs fed a folacin deficient diet with and without sulfonamide, J. Nutr., 108 836. 

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. 

Histidine ammonia lyase (histidase) (EC 4.3.1.3). Failure to form urocanic acid from histidine. Histidine elevated in blood and cerebrospinal fluid. Increased urinary histidine, imidazolepyruvate, imidazolelactate and imidazoleacetate. Formiminoglutamate not excreted after histidine load. Usually benign. Mental retardation rare. 

Increased urinary formiminoglutamic acid in the absence of folic acid deficiency or cobalamine C disease is indicative of formiminotransferase deficiency. Accumulation of imidazolonepropionic acid is not observed, but there is an abnormal excretion of its oxidation product, hydantoin-5-pro-pionic acid. Loading tests with histidine will enhance the excretion. Confirmation of the defect is made by enzyme analysis probably the liver is the only suitable tissue. Affected patients were mentally retarded and/or had convulsions however, a number of healthy siblings with the biochemical abnormality have been described. 

An in vivo test for the investigation of suspected folic acid deficiency. The normal metabolism of histidine contains a step in which formiminoglutamic acid (FIGLU) is converted to glutamate by an enzyme which uses folate as a cofactor. In patients with folate deficiency, administration of oral histidine results in a greater than normal urinary excretion of FIGLU. 

In addition to the accumulation of 5-methyl THF in the sera of patients with vitamin B12 deficiency (Herbert and Zalusky, 1962), an increase is seen in the excretion of formiminoglutamic acid (Silverman and Pitney, 1958 Rabinowitz and Tabor, 1958), formate (Friedman, 1954 Stokstad, 1966) and carboxamide (McGeer, 1965). 

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. 

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