5,10-Methenyl tetrahydrofolate

Pomper BK, Vorholt JA, Chistoserdova L, et al. 1999. A methenyl tetrahydromethanopterin cyclohydrolase and a methenyl tetrahydrofolate cyclohydrolase in Methylobacterium extorquens AMI. Eur J Biochem 261 475-80. 

Methylene-, methenyl-, and 10-formyl-tetrahydrofolates are freely interconvertible. The two activities involved - methylene-tetrahydrofolate dehydrogenase and methenyl-tetrahydrofolate cyclohydrolase - form a trifunctional enzyme with 10-formyl-tetrahydrofolate synthetase (Paukert et al., 1976). This means that single-carbon fragments entering the folate pool in any form other than as methyl-tetrahydrofolate can be readily available for any of the biosynthetic reactions shown in Figure 10.4. 

The conversion of 5-formyl-tetrahydrofolate to methenyl-tetrahydrofolate, catalyzed by 5-formyl-tetrahydrofolate cyclohydrolase, is important. Although 5-formyl-tetrahydrofolate is the most commonly used pharmaceutical preparation of the vitamin, a relatively large proportion of orally administered... 

The conversion of 5-formyl-tetrahydrofolate to methenyl-tetrahydrofolate, catalyzed by 5-formyl-tetrahydrofolate cyclohydrolase, is important. Although... 

The entire glycine molecule is added to the growing purine precursor. Then C8 is added by methenyl tetrahydrofolate, N3 by glutamine, C6 by C02, N1 by aspartate, and C2 by formyl tetrahydrofolate (see Figure 7-20, bottom). 

Human IMP synthase has a subunit molecular weight of 62.1 kDa and associates as a dimer. A trifunctional enzyme, Cj-THF synthase, containing (V °-methenyl tetrahydrofolate (5,10-CH-THF) cyclohydrolase and A °-formyl tetrahydrofolate (lO-CHO-THF) synthetase, catalyzes the reactions 5,10-CH2-THF 5,10-CH-THF and THF —> lO-CHO-THF. The A °-CH-THF produced is a substrate for GAR and AICAR transformylases catalyzing reactions 3 and 9 of the pathway. In higher eukaryotes, the dehydrogenase and cyclohydrolase activities are located in one domain of the protein, which is fused to a larger synthetase domain, forming a trifunctional enzyme. 

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. 

The coenzymes are formed from dihydrofolic acid by the enzyme dihydrofolate hydrogenase which gives tetrahydrofolic acid (Osborn, Freeman and Huennekens, 1958), and this is then modified by various one-carbon substituents. The coenzyme for the insertion of C-2 into purines, i.e. for the formylation of the ribotide 9 14) to give (9.1 s)y is -formyl-5563738-tetrahydrofolic acid. For the earlier stage of the insertion of C-8, i.e. for the formylation of glycinamide ribotide to form (eventually) (9./ ), the coenzyme is -methenyl-tetrahydrofolic acid (9-/6). The... 

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