Formyl coenzyme

S ATP -I- formate <1> (<1> the product formyl phosphate serves as formyl donor for the synthesis of formyl coenzyme A in a reaction catalyzed by phosphate acetyltransferase [1]) (Reversibility <1> [1]) [1]... 

Sly, W.S. Stadtman, E.R. (1963) J. Biol. Chem. 238, 2632-2638. Formate metabolism. 1. Formyl coenzyme A, an intermediate in the formate-dependent decomposition of acetyl-phosphate in Clostridium kluyveri. 

A/ -Methoxycarbonyl-2-pyrroline undergoes Vilsmeier formylation and Friedel-Crafts acylation in the 3-position (82TL1201). In an attempt to prepare a chloropyrroline by chlorination of 2-pyrrolidone, the product (234) was obtained in 62% yield (8UOC4076). At pH 7, two molecules of 2,3-dihydropyrrole add together to give (235), thus exemplifying the dual characteristics of 2,3-dihydropyrroles as imines and enamines. The ability of pyrrolines to react with nucleophiles is central to their biosynthetic role. For example, addition of acetoacetic acid (possibly as its coenzyme A ester) to pyrroline is a key step in the biosynthesis of the alkaloid hygrine (236). 

Folic acid is a coenzyme involved in the metabolism of one-carbon fragments the methyl, hydroxymethyl, and formyl groups. An inadequate intake of folic acid during pregnancy can result in spina bifida. 

The reductant is the deazaflavin F420 and the reactions parallel those for conversion of formyl-THF to methyl-THF (Fig. 15-18).431 440b 441 The methyl group of methyl-H4MPT is then transferred to the sulfur atom of the thiolate anion of coenzyme M, from which it is reduced off as CH4. This is a complex process requiring the nickel-containing F430,... 

One-carbon fragments in various oxidation stales are (I) formyl l—CHO) (2) hydroxymethyl l-CHiOH) and (3) methyl t-CHj). The coenzyme forms of folie acid have one of these groups attached to either the 5-N or 10-N of telrahydrofolic acid. One folic acid... 

The tetrahydrofolates do not function as tightly enzyme-bound coenzymes. Rather, they function as cosubstrates for a variety of enzymes associated with one-carbon metabolism. /Vl0-formyltetrahydrofolate is produced enzymatically from tetrahydrofolate and formate in an ATP-linked process in which formate is activated by phosphorylation to formyl phosphate the formyl group of formyl phosphate is then transferred to A10 of tetrahydrofolate. A10-Formyltetrahydrofolate is a formyl donor substrate for some enzymes and is interconvertible with A5,A10-methenyltetrahydrofolate by the action of cyclohydrolase. 

Deazaflavines and pyrido[2,3-d 6,5-d ]dipyrimidines, which possess an ability to oxidize an alcohol, are obtained from 6-chloro-5-formyl-3-methyluracil and anilines or 6-aminopyrimidines [76CC203 78CPB3208 81JA5943 84TL(25) 1741 86JHC241]. This method is applied to the total synthesis of coenzyme factor 420 [90JCS(P1)253] (Scheme 100). 

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 UV-visible spectra of methanofuran, and its formyl form, are very similar, with an absorbance peak at 273 run, and a shoulder at 280 nm, with a maximum at <240 nm [87-89,100]. This coenzyme is stable to both boiling and air exposure. 

Both methenyl- and 5-formyl derivatives are reasonably stable in air [109] under acidic conditions, 5-formyl-H4MPT is converted back to methenyl-H4MPT, and under very basic conditions methenyl-H4MPT is converted to the oxygen-sensitive 10-formyl derivative [122]. The various one-carbon-H4MPT derivatives can be assayed by spectral changes in some cases, or by HPLC analysis [2,109,122]. No H4MPT coenzymes discussed above have been reported to be bound to enzymes. 

Fig. 7. Proposed function of electrochemical H and Na" potentials in energy conservation coupled to CH4 formation from CO2/H2. The Na+/H antiporter is involved in the generation of from A/iNa ". CHO-MFR, formyl-methanofuran CH2=H4MPT, methylene-tetrahydromethanopterin CH3-H4MPT, methyl-tetrahydromethanopterin CH3-S-C0M, methyl-coenzyme M. The hatched boxes indicate membrane-bound electron transport chains or membrane-bound methyltransferase catalyzing either Na or translocation (see Figs. 5, 6 and 12). ATP is synthesized via membrane-bound H -translocating ATP synthase. The stoichiometries of Na" and translocation were taken from refs. [105,107,167]. x, y and z are unknown stoichiometric factors.

Acetate is synthesized via the acetyl-CoA pathway (for recent reviews see refs. [190-192]) one molecule CO2 is reduced via formyl-tetrahydrofolate (formyl-H4F) and methylene—H4F to methyl-H4F, a second one is reduced to a enzyme-bound carbonyl. The methyl group is condensed with the carbonyl group and coenzyme A (CoA) to acetyl-CoA. Acetyl-CoA is then converted to acetate, and ATP is formed in the acetate kinase reaction. 

Thus, acetyl-CoA oxidation via the acetyl-CoA pathway in Archaeoglobus fulgidus differs from that of eubacterial sulfate reducers in several respects It involves tetrahydromethanopterin rather than tetrahydrofolate (H4F) as Ci carrier, and formyl-methanofiiran rather than free formate as an intermediate. Furthermore, coenzyme F420 serves as electron acceptor of two dehydrogenases. In eubacterial sulfate reducers the oxidation of acetyl-CoA to CO2 involves the exergonic formyl-H4F conversion to formate and H4F, which is catalyzed by formyl-H4F synthetase this reaction is coupled with ATP synthesis by the mechanism of substrate level phosphorylation (for literature see refs. [90,209]). The different mechanism of formyl-H4MPT conversion to... 

Folic acid is itself inactive it is converted into the biologically active coenzyme, tetrahydrofolic acid, which is important in the biosynthesis of amino acids and DNA and therefore in cell division. The formyl derivative of tetrahydrofolic acid is folinic acid and this is used to bypass the block when the body fails to effect the conversion of folic acid (see Folic acid antagonists, p. 606). Ascorbic acid protects the active tetrahydrofolic acid from oxidation the anaemia of scurvy, although usually normoblastic, may be megaloblastic due to deficiency of tetrahydrofolic acid. 

The metabolism of folic acid involves reduction of the pterin ting to different forms of tetrahydrofolylglutamate. The reduction is catalyzed by dihydtofolate reductase and NADPH functions as a hydrogen donor. The metabolic roles of the folate coenzymes are to serve as acceptors or donors of one-carbon units in a variety of reactions. These one-carbon units exist in different oxidation states and include methanol, formaldehyde, and formate. The resulting tetrahydrofolylglutamate is an enzyme cofactor in amino acid metabolism and in the biosynthesis of purine and pyrimidines (10,96). The one-carbon unit is attached at either the N-5 or N-10 position. The activated one-carbon unit of 5,10-methylene-H folate (5) is a substrate of T-synthase, an important enzyme of growing cells. 5-10-Methylene-H folate (5) is reduced to 5-methyl-H,j folate (4) and is used in methionine biosynthesis. Alternatively, it can be oxidized to 10-formyl-H folate (7) for use in the purine biosynthetic pathway. 

The coenzyme form of folic acid is tetra hydro folic acid (Figure 6.9). Tetrahydro folic acid is associated with one carbon metabolism. The tetrahydro folic acid serves as a carrier of single carbon moieties such as formyl, methenyl, methylene, formyl or methyl group. (Figure 6.10). It is involved in the biosynthesis of purines, pyrimidines, serine, methionine and glycine. 

This mechanism is quite general for this substitution reaction in transition metal hydride-carbonyl complexes [52]. It is also known for intramolecular oxidative addition of a C-H bond [53], heterobimetallic elimination of methane [54], insertion of olefins [55], silylenes [56], and CO [57] into M-H bonds, extmsion of CO from metal-formyl complexes [11] and coenzyme B12- dependent rearrangements [58]. Likewise, the reduction of alkyl halides by metal hydrides often proceeds according to the ATC mechanism with both H-atom and halogen-atom transfer in the propagation steps [4, 53]. 

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