Acetyl-CoA pathway

CODH from acetogens found to catalyze acetyl-CoA synthesis and nickel proposed to be the active site of CO oxidation and acetyl-CoA synthesis. CODH found to contain a heterometallic cluster consisting of nickel and iron that binds CO and proposed to be the active site of acetyl-CoA synthesis. Growth of acetogens on nitrate disables the acetyl-CoA pathway. ... 

In Hg-resistant bacteria that are resistant to organic forms of Hg such as phenylmercuric acetate and methylmercury chloride, lyases are involved in the fission of the C-Hg to form Hg + and benzene or methane, and the enzyme has been partly purified (Schottel 1978). The Hg + may then be reduced to nontoxic Hg°. The situation under anaerobic conditions for sulfate-reducing bacteria is complicated by the possibility of both methylation and demethylation in the same strain (Pak and Bartha 1998), plausibly by operation of the acetyl-CoA pathway (Choi et al. 1994 Ekstrom et al. 2003). Under anaerobic conditions, demethylation, though not methylation, has been reported for a methanogen (Pak and Bartha 1998). 

Figure 13.2. The preferred flow of reductant from aromatic aldehydes to the acetyl-CoA pathway by the acetogen C. formicoaceticum. THF, tetrahydrofolate brackets, the Ci unit is bound to a cofactor or structurally associated with an enzyme.

For many decades, the capacity of acetogens to reduce CO2 to acetate and the thermodynamics of the acetyl-CoA pathway casts the acetogens as somewhat obscure specialists and thermodynamically disadvantaged... 

Ljungdahl LG. 1994. The acetyl-CoA pathway and the chemiosmotic generation of ATP during acetogenesis. In Drake HL, editor. Acetogenesis, New York Chapman Hall, p 63-87. 

Ragsdale SW. 1991. Enzymology of acetyl-CoA pathway of CO2 fixation. Crit Rev Biochem Mol Biol 26 261-300. 

Figure 22. Pyruvate derivation and acetyi CoA synthesis. Observe that pyruvate, and subsequently the acetyl CoA pathway, has chain roots in the primary metabolism. Pyruvate can also be synthetized by conversion reactions. The secondary acetyl CoA is constructed as a building block on the pyruvate and glycolysis.

Reductive acetyl-CoA pathway 4-5 3 NAD(P)H, 2-3 ferredoxin, 1 H2 (in methanogens) Acetyl-CoA synthase/ CO dehydrogenase, formate dehydrogenase, pyruvate synthase C02 Acetyl-CoA, pyruvate Acetyl-CoA synthase/CO dehydrogenase, enzymes reducing C02 to methyltetrahydropterin... 

The Reductive Acetyl-CoA Pathway (Wood-Ljungdahl Pathway)... 

This is a noncyclic pathway that also results in the fixation of two molecules of C02 to form acetyl-CoA. It was elucidated by Wood, Ljungdahl, Thauer and others as a pathway which is used by acetogenic bacteria to synthesize acetate from C02 in their energy metabolism [21]. The acetyl-CoA pathway resembles the Monsanto process of acetate synthesis from CO and methanol, with one molecule of C02 being reduced to the level of methyltetrahydropterin, while another C02 molecule is reduced to the level of carbon monoxide in the reaction catalyzed by the nickel-dependent carbon monoxide dehydrogenase (Figure 3.3). 

The reductive acetyl-CoA pathway is unique in several aspects. For example, the pathway makes extensive use of coenzymes (tetrahydropterin, cobalamin) and of... 

Figure 3.3 Reductive acetyl-CoA pathway. CD, CO dehydrogenase/acetyl-CoA-synthase , pyruvate ferredoxin oxidoreductase.

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... 

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