Reductive TCA

A reversed, reductive TCA cycle would require energy input to drive it. What might have been the thermodynamic driving force for such a cycle Wachtershanser hypothesizes that the anaerobic reaction of FeS and H9S to form insoluble FeS9 (pyrite, also known as fool s gold) in the prebiotic milieu could have been the driving reaction ... 

The only cultivated AOA, Nitrospumilus maritimus, depends on CO2 as its only carbon source and the presence of even low levels of organic carbon were inhibitory to growth. The pathway of CO2 fixation is, however, unknown. Hyperthermophilic Crenarchaeota generally utilize a 3-hydroxypropionate pathway or a reductive TCA cycle for autotrophic carbon fixation. Another cultivated marine Crenarchaeota strain, Cenarchaeum symbiosum, a sponge symbiont, appears to use the 3-hydroxypropionate pathway. It cannot be concluded on this basis which pathway is used by the AOA, but it very likely that is not the Calvin cycle. N. maritimus had a minimal generation time of 21 h, longer but roughly on the same scale as AOB. 

Grice et al., 1996b). This isotopic enrichment is typical for the reductive TCA cycle, the pathway of CO2 fixation followed by Chlorobiaceae (Section 8.03.6.1.4). 

Reductive TCA cycle in an aerobic bacterium, Hydrogenobacter thermophilus strain TK-6... 

Purification and characterization of components involved in the reductive TCA cycle in H. thermophilus strain TK-6 confirmed the operation of the cycle. 

Figure 18.1. The reductive TCA cycle (bold roman font) as an engine of synthesis of the major classes of biomolecules (bold italic). Synthesis of categories usually begins with a specific molecule (lightface).

Direct proof that this reductive TCA pathway participates in fumaric acid production came from C NMR experiments using [1- C] and [U- C] glucose as a carbon source for R. oryzae (Kenealy et al., 1986). The unexpectedly high fumaric acid molar yields can thus be explained in terms of pyruvate carboxylation as the initial reaction of a reductive TCA pathway (Figure 15.1). 

But once the notion of a cytosolic reductive TCA pathway is accepted, the question is why the experimentally obtained yields of C4 organic acids (120-145%, see above, 15.3.1) are lower than the theoretical maximal yield of 200% calculated for this pathway. A plausible explanation for this is that the fungus must divert some of the pyruvic acid carbon to mitochondria and to the oxidative TCA cycle to obtain energy required for maintenance requirements and limited cellular growth (Figure 15.1). 

The operation of the cytosolic reductive TCA pathway for fumaric acid production in R. oryzae raises the question as to the unique role of the cytosolic fumarase in this fungus. 

The reductive TCA cycle uses CO2 for producing acetyl-CoA [28, 29]. Two CO2 units are converted in each cycle into acetyl-CoA using one ATP and four NAD(P) H units. The full cycle was first reported to be found in a green sulfur photosynthetic bacterium Chlorobium limicola) and was later also found to operate in Aquificales, Archeal Crenarcheota, and various types of proteobacteria. 

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... 

Figure 17.15 Major metabolic pathways involved in SA production in Saccbaromyces cerevisiae. Bold arrows indicate the major routes for succinate synthesis starting from glucose (a) via the reductive TCA cycle and (b) via the giyoxyiate cycle. PEP, phos-phoenolpyruvate OAA, oxaloacetate MAL, malate FUM, fumarate Suc-CoA, sucdnyl-CoA cr-KG, cr-ketoglutarate ICT, isodtrate CIT, citrate, ppc, PEP carboxykinase pyc, pyruvate carboxylase pyk, pyruvate kinase ...

---