Formimino tetrahydrofolate

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

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,... 

The catabolism of histidine leads to the formation of formiminoglutamate (section 11.11.6). The formimino group is transferred onto tetrahydrofolate to form formimino-tetrahydrofolate, which is subsequently deaminated to form methenyl-tetrahydrofolate. 

Tetrahydrofolate can carry one-carbon fragments attached to N-5 (formyl, formimino, or methyl groups), N-10 (formyl group), or bridging N-5 to N-10 (methylene or methenyl groups). 5-Formyl-tetrahydrofolate is more stable than folate and is therefore used pharma-... 

Catabolism of histidine. The first steps of the major degradative pathway for histidine metabolism have already been discussed. Elimination of ammonia, followed by hydration and ring cleavage to formiminoglutamate, involves unusual reactions (Eq. 25-14)252 which have been discussed earlier. Transfer of the formimino group to tetrahydrofolic acid and its further metabolism have also been considered (Chapter 15). 

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

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.)...

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 formimino transferase. 

Histidine is converted into 4-imidazolone 5-propionate (Figure 23.24). The amide bond in the ring of this intermediate is hydrolyzed to the TV-formimino derivative of glutamate, which is then converted into glutamate by transfer of its formimino group to tetrahydrofolate, a carrier of activated one-carbon units (Section 24.2.6). 

The one-carbon group carried by tetrahydrofolate is bonded to its N-5 or N-10 nitrogen atom (denoted as TV and TV i ) or to both. This unit can exist in three oxidation states (Table 24.2). The most-reduced form carries a methyl group, whereas the intermediate form carries a methylene group. More-oxidized forms carry a formyl, formimino, or methenyl group. The fully oxidized one-carbon unit, CO2, is carried by biotin rather than by tetrahydrofolate. 

Tetrahydrofolate, a carrier of activated one-carbon units, plays an important role in the metabolism of amino acids and nucleotides. This coenzyme carries one-carbon units at three oxidation states, which are interconvertible most reduced—methyl intermediate—methylene and most oxidized—formyl, formimino, and methenyl. The major donor of activated methyl groups is -adenosylmethionine, which is synthesized by the transfer of an adenosyl group from ATP to the sulfur atom of methionine. -Adenosylhomocysteine is formed when the activated methyl group is transferred to an acceptor. It is hydrolyzed to adenosine and homocysteine, the latter of which is then methylated to methionine to complete the activated methyl cycle. 

Histidine can be converted to formiminoglutamate (FIGLU). The formimino group is transferred to tetrahydrofolate (FH4), and the remaining five carbons form glutamate. 

Tetrahydrofolate (THF) is the major source of 1-carbon units used in the biosynthesis of many important biological molecules. This cofactor is derived from the vitamin folic acid and is a carrier of activated 1-carbon units at various oxidation levels (methyl, methylene, formyl, formimino, and methenyl). These compounds can be interconverted as required by the cellular process. The major donor of the 1-carbon unit is serine in the foUowing reaction ... 

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. 

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 . ... 

Folic Acid in the Degradation of Purines. The conversion of formiminoglycine to glycine is accomplished by a transfer of the formimino group to tetrahydrofolic acid (THF) (VI). The formimino group is assigned to... 

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