5.10- Methenyl-5,6,7,8-tetrahydrofolic acid

Methenyl-5,6,7,8-tetrahydrofolic acid, chloride hydrochloride dihydrate... 

Methenyl-5,6,7,8-tetrahydrofolic acid, chloride hydrochloride dihydrate (20 g) was added in one portion to 100 ml water at 60°C followed by N,N-diethylethanolamine (14.9 g) which adjusted the pH to 6. The mixture was maintained at reflux for 5 hours and the pH kept between 5.7 and 6.2 by addition of N,N-diethylethanolamine. The mixture was cooled, synthetic magnesium silicate (15 g) added and slurried, and filtered through celite and diluted with 40 ml SD3A (95% ethanol with 5% methanol). The filtrate was kept at -5°C for 16 hours, aqueous calcium chloride (4.0 g) was added dropwise to the cold filtrate, and the precipitate filtered, washed with SD3A (100 ml) and with ethyl acetate (100 ml) and dried under reduced pressure. 

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... 

Tetrahydrofolic acid then functions as a carrier of one-carbon groups for amino acid and nucleotide metabolism. The basic ring system is able to transfer methyl, methylene, methenyl, or formyl groups, and it utilizes slightly different reagents as appropriate. These are shown here for convenience, we have left out the benzoic acid-glutamic acid portion of the structure. These compounds are all interrelated, but we are not going to delve any deeper into the actual biochemical relationships. 

A reduced form of folic acid (tetrahydrofolic acid, FH4) is active in so-called one-carbon metabolism. A formyl group may be substituted on N(5) or N(io) and the N(5)-N(io) methenyl derivative (Figure 36) is also active. Reactions involving the introduction of one-carbon fragments include the conversion of glycine to serine (Section V.C.3), ethanolamine to choline (Section V.C.3) and the introduction of C(8) of the purine nucleus (Section V.D.3). 

This enzyme converts formiminoglutamic acid to glutamic acid 266, 267). The formimino group is transferred to form 5-formiminotetra-hydrofolic acid. This in turn is transformed by two other enzymes, first to yield 6,10-methenyl-FH4 and NHs, and subsequently 10-formyl-FH4 (FH4 for tetrahydrofolic acid). 

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. 

The six one-carbon substituents of tetrahydrofolate. The oxidation state is the same in the one-carbon moiety of N -formyl, N -formyl, and N, N" -methenyl FH4. N -FormyI FH4 is required for de novo synthesis of purine nucleotides, whereas N, N -methylene FH4 is needed for formation of thymidilic acid. 

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 ... 

Amino acids are precursors of many phy siologically important biomolecules. Many of the processes that synthesize these molecules involve the transfer of carbon groups. Because many of these transfers involve one-carbon groups (e.g., methyl, methylene, methenyl, and formyl), the overall process is referred to as one-carbon metabolism. S-Adenosylmethionine (SAM) and tetrahydrofolate (THF) are the most important carriers of one-carbon groups. 

As shown in Figure 11.19, tetrahydrofolate can carry one-carbon fragments attached to N-5 (formyl, formimino or methyl groups), N-10 (formyl) or bridging N-5—N-10 (methylene or methenyl groups). 5-Formyl-tetrahydrofolate is more stable to atmospheric oxidation than folate itself, and is therefore commonly used in pharmaceutical preparations it is also known as folinic acid, and the synthetic (racemic) compound as leucovorin. 

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