Formimidoyltetrahydrofolate cyclodeaminase explained

In enzymology, a formimidoyltetrahydrofolate cyclodeaminase is an enzyme that catalyzes the chemical reaction

5-formimidoyltetrahydrofolate

5,10-methenyltetrahydrofolate + NH₃

Hence, this enzyme has one substrate, 5-formimidoyltetrahydrofolate, and two products, 5,10-methenyltetrahydrofolate and NH₃.^[1]

This enzyme belongs to the family of lyases, specifically ammonia lyases, which cleave carbon-nitrogen bonds. The systematic name of this enzyme class is 5-formimidoyltetrahydrofolate ammonia-lyase (cyclizing 5,10-methenyltetrahydrofolate-forming). Other names in common use include formiminotetrahydrofolate cyclodeaminase, and 5-formimidoyltetrahydrofolate ammonia-lyase (cyclizing). This enzyme participates in folate metabolism by catabolising histidine and adding to the C₁-tetrahydrofolate pool.

In mammals, this enzyme can be found as part of a bifunctional enzyme in a single polypeptide with glutamate formimidoyltransferase (EC 2.1.2.5), the enzyme activity that catalyses the previous step in the histidine catabolic pathway.^[2] This arrangement allows the 5-formimidoyltetrahydrofolate intermediate to move directly from one active site to another without being released into solution, in a process called substrate channeling.^[3]

Structural studies

As of late 2007, 3 structures have been solved for this class of enzymes, with PDB accession codes,, and .

Notes and References

1. Rabinowitz JC . Pricer WE . 1956 . Formiminotetrahydrofolic acid and methenyltetrahydrofolic acid as intermediates in the formation of N10-formyltetrahydrofolic acid . J. Am. Chem. Soc. . 78 . 5702 - 5704 . 10.1021/ja01602a073 . 21 .
2. MacKenzie RE, Aldridge M, Paquin J . The bifunctional enzyme formiminotransferase-cyclodeaminase is a tetramer of dimers . J. Biol. Chem. . 255 . 19 . 9474–8 . 10 October 1980. 10.1016/S0021-9258(19)70586-9 . 7410436 . free .
3. Kohls D, Sulea T, Purisima EO, MacKenzie RE, Vrielink A . The crystal structure of the formiminotransferase domain of formiminotransferase-cyclodeaminase: implications for substrate channeling in a bifunctional enzyme . Structure . 8 . 1 . 35–46 . 2000 . 10673422 . 10.1016/S0969-2126(00)00078-2. free .