Formiminotransferase

GLYCINE SYNTHASE GLYCINE DECARBOXYLASE GLYCINE FORMIMINOTRANSFERASE [ N]Glycine kinetics,... 

Malvagia S, la Marca G, Casetta B, et al (2006) Falsely elevated C4-carnitine as expression of glutamate formiminotransferase deficiency in tandem mass spectrometry newborn screening. J Mass Spectrom 41 263-265... 

CFD is further associated with the following inherited metabolic disorders 5,10-methylen-tetrahydrofolate reductase (MTHFR) deficiency [7], 3-phos-phoglycerate dehydrogenase (PGDH) deficiency [8], dihydropteridine reductase (DHPR) deficiency [9], as well as with Rett syndrome [10], and Aicardi-Gou res Syndrome [11]. Furthermore, folate deficiency may be associated with congenital folate malabsorption, severe malnutrition, and formiminotransferase deficiency. 

Figure 10.6. Catabolism of histidine - basis of the FIGLU test for folate status. Histidase, EC 4.3.1.3 urocanase, EC 4.2.1.49 FIGLU formiminotransferase, EC 2.1.2.5. THF, tetrahydrofolate.

A single bifunctional enzyme catalyzes the FIGLU formiminotransferase and formiminofolate cyclodeaminase reactions, so there is little or no free formimino-tetrahydrofolate in tissues under normal conditions. The two catalytic sites are separate, and with tetrahydrofolate monoglutamate, there is release of the formimino derivative. However, when polyglutamates are used,... 

Formylglutamate can transfer its formyl group directly onto tetrahydrofolate to yield 5-formyl-tetrahydrofolate. Formyl-glutamate is not a normal physiological intermediate, and the formation of 5-formyl-tetrahydrofolate is probably a side reaction of FIGLU formiminotransferase. 

Paquin J, Baugh CM, and MacKenzie RE (1985) Channeling between the active sites of formiminotransferase-cyclodeaminase. Binding and kinetic studies. Journal of Biological Chemistry 2SO, 14925-31. 

F-13) Formiminotransferase deficiency. This results in increased urinary levels of FIGlu (for-miminoglutamate). The patient may have significant neurological and other physical defects. FIGlu is also an indicator for folate deficiency. Just as xanthurenate is for Be deficiency (see 57), and urinary methylmalonate is for Bi2 deficiency (see 72). 

Similarly, a deficiency of glutamate formiminotransferase leads to accumulation of Figlu and high levels of serum folate. 

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... 

A total of 10 patients have now been described with formiminotransferase deficiency. Some have had a variable degree of mental retardation and a severe anemia while others have been asymptomatic. Arakana and his colleagues described five patients (two of whom were brothers) and all were severely mentally retarded (A9, AlO). 

It is not possible to say if all of these patients are true examples of formiminotransferase deficiency. A degree of clinical variation could be expected and this would depend on how much of the active enzyme was available. The patients described by Perry excreted much more formimino-... 

A8. Arakawa, T., Tamura, T., Higashi, O., Ohara, K., Tanno, K., Honda, Y., Narisawa, K., Konno, T., Wada, Y., Sato, Y., and Mizuno, T., Formiminotransferase deficiency syndrome associated with megaloblastic anaemia responsive to pyridoxine or folic acid. Tohoku J. Exp. Med. 94, 3-16 (1968). 

---