Reductive acetyl-CoA pathway

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)... 

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.

Pathways of autotrophic CO2 fixation A Reductive citric acid cycle Reductive acetyl CoA pathway I Reductive hydroxypropionante pathway Cathin-Bonion cycle... 

If we compare the reductive acetyl CoA pathway with the Calvin cycle and the reductive TCA pathways, we see that it presents some differences it is a linear unidirectional pathway, through which two molecules of CO2 are reductively... 

Scheme 9.4 Carbon dioxide fixation via the reductive acetyl-CoA pathway. Adapted from...

Another model is based on the fact that the genetic code shows a number of regularities, some of which have already been mentioned above. It is suspected that codons beginning with C, A or U code for amino acids which were formed from a-ketoacids (or a-ketoglutarate, 1-KG), oxalacetate (OAA) and pyruvate. This new model, which is quite different from the previous models, assumes that a covalent complex formed from two nucleotides acted as a catalyst for chemical reactions such as the reductive amination of a-ketoacids, pyruvate and OAA. More recent analyses suggest that the rTCA cycle (see Sect. 7.3) could have served as a source of simple a-ketoacids, including glyoxylate, pyruvate, OAA and a-KG. a-Ketoacids could, however, also have been formed via a reductive acetyl-CoA reaction pathway. The bases of the two nucleotides specify the amino acid synthesized and were retained until the modern three-letter codes were established (Copley et al., 2005). 

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.

All microbes, including chemoorganohetero-trophs, possess some ability to engage in reversible carboxylation (i.e., CO2-C assimilation into an organic compound) and decarboxylation reactions, some of which lead to the incorporation of a significant amount of CO2 (Wood, 1985). Here, we briefly consider the biochemical pathways that photo- and chemolithotrophic bacteria deploy in order to produce the majority of their biomass. The four major C02-fixing pathways are the Calvin cycle, the acetyl-CoA pathway, the reductive tricarboxylic acid (TCA) cycle, and the 3-hydroxypriopionate cycle. 

Reaction 2 above shows the reductive formation of acetate from CO2. This occurs via the acetyl-CoA pathway so called beeause the acetyl group of acetyl-CoA is the first 2-carbon moiety in which both carbons originate from CO2. The acetyl-CoA pathway is now recognized as an autotrophic pathway of CO2 fixation. The pathway is outlined in Fig. 1. Carbon dioxide enters the pathway via two reductive reactions. One, catalyzed by an NADP-dependent formate hydrogenase (FDH), leads to the formation of formate that, in a series of reaetions involving tetrahydrofolate (THF)intermediates is reduced to methyl-THF, the methyl group of which is... 

Cobalamin-catalyzed reactions are generally classified into two groups methylcob-alamin-dependent reactions (Table 1, entry 1 to 3) and coenzyme Bi2-dependent rearrangements (Table 1, entry 4 to 11). The first group includes the biosynthesis of methionine from homocysteine, the reduction of CO2 to acetic acid via an acetyl-CoA pathway, and the biosynthesis of CH4 also via an acetyl-CoA pathway. ... 

This acetyl-CoA pathway (or Wood-Ljungdahl pathway) involves reduction by H2 of one of the two molecules of CO2 to the methyl group of methyl-tetrahydromethanopterin in methanogens and of methyltetra-hydrofolate in acetogens. The pathway utilized by methanogens is illustrated in Fig. 15-22. ... 

Whereas catabolism is fundamentally an oxidative process, anabolism is, by its contrasting nature, reductive. The biosynthesis of the complex constituents of the cell begins at the level of intermediates derived from the degradative pathways of catabolism or, less commonly, biosynthesis begins with oxidized substances available in the inanimate environment, such as carbon dioxide. When the hydrocarbon chains of fatty acids are assembled from acetyl-CoA units, activated hydrogens are needed to reduce the carbonyl (C=0) carbon of acetyl-CoA into a —CHg— at every other position along the chain. When glucose is... 

One of these alternate models, postulated by Gunter Wachtershanser, involves an archaic version of the TCA cycle running in the reverse (reductive) direction. Reversal of the TCA cycle results in assimilation of CO9 and fixation of carbon as shown. For each turn of the reversed cycle, two carbons are fixed in the formation of isocitrate and two more are fixed in the reductive transformation of acetyl-CoA to oxaloacetate. Thus, for every succinate that enters the reversed cycle, two succinates are returned, making the cycle highly antocatalytic. Because TCA cycle intermediates are involved in many biosynthetic pathways (see Section 20.13), a reversed TCA cycle would be a bountiful and broad source of metabolic substrates. 

Ketone bodies are formed in the liver mitochondria by the condensation of three acetyl-CoA units. The mechanism of ketone body formation is one of those pathways that doesn t look like a very good way to do things. Two acetyl-CoAs are condensed to form acetoacetyl-CoA. We could have had an enzyme that just hydrolyzed the acetoacetyl-CoA directly to acetoacetate, but no, it s got to be done in a more complicated fashion. The acetoacetyl-CoA is condensed with another acetyl-CoA to give hydroxymethylglutaryl-CoA (HMG-CoA). This is then split by HMG-CoA lyase to acetyl-CoA and acetoacetate. The hydroxybutyrate arises from acetoacetate by reduction. The overall sum of ketone body formation is the generation of acetoacetate (or hydroxybutyrate) and the freeing-up of the 2 CoAs that were trapped as acetyl-CoA. 

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