Part of the cell · Carbon fixation and precursor metabolism
Building carbon into molecules
On the cell picture: Central carbon metabolism
The cell is given carbon dioxide gas and nothing else to build with. These proteins run the cycle that pulls CO₂ out of the water and turns it into the first carbon skeletons every other pathway starts from.
Proteins in the model: 9
Part of the model's 1051 proteins. Each group below is a book group, counted in the working count after the repeats and non-first-cell groups were removed. The proteins are not yet matched gene by gene.
| Group | Proteins |
|---|---|
| Carbon Monoxide Dehydrogenase/Acetyl-CoA Synthase (CODH/ACS) | 2 |
| rTCA cycle (excluding standard TCA cycle enzymes) | 4 |
| Wood-Ljungdahl pathway | 2 |
| Carbonic anhydrase | 1 |
Its pathways
- Reductive TCA machineryatlas pathway11
- Sugar-phosphate supplyatlas pathway5
- Pyruvate and acetyl-CoAatlas pathway4
- Lipid A and outer envelopeatlas pathway3
- Ribose and PRPP supplyatlas pathway1
- Glycolysis / GluconeogenesisKEGG map7
- Amino sugar and nucleotide sugar metabolismKEGG map5
- Pentose phosphate pathwayKEGG map3
- Not yet placed in a pathwayto sort7
If it fails
Nothing can be built. Every biosynthetic pathway loses its starting material at the same moment.
Starves of a building block · 1–2 generations
What it depends on
- Turning hydrogen into usable energyATP and reducing equivalents support energy-requiring carbon assimilation and precursor production. The exact coupling depends on the chosen fixation pathway.Book pp. 546–550
- Manufacturing cofactors and vitaminsCoA and one-carbon cofactors enable carbon transfer and acetyl-CoA metabolism in the proposed network.Book pp. 498, 546–550
- Loading metals into enzymesCODH/ACS and other selected carbon-metabolism enzymes require correctly assembled metal centers.Book pp. 384–407, 498
What it supplies
- Manufacturing cofactors and vitaminsCarbon intermediates supply the molecular skeletons used to synthesize cofactors.Book pp. 498–499
- Making DNA and RNA lettersCarbon precursors supply the ribose and ring-building substrates needed for nucleotide synthesis.Book pp. 499–500
- Making the twenty amino acidsCentral metabolism provides carbon skeletons for amino acid biosynthesis.Book pp. 498–500
- Building and maintaining the membraneAcetyl-CoA and other carbon intermediates feed fatty acid and membrane lipid synthesis.Book pp. 500–501
Dependencies are curated from the book at the level of the map’s systems and are not measured protein contacts. See all systems together.
How it is built and controlled
Counts from UniProt annotations of this group’s proteins.
Its place in the control layer
None of this group’s proteins appear in the information, signaling, regulation, machine-signal or assembly lists.
From the control-layer pages. Which genes a regulator controls is mostly inferred from related bacteria, because Aquifex has no genetic system for testing it directly.
Origins
What needs to be explained
How did carbon capture, energy coupling and catalyst regeneration become compatible in a sustained network?
What needs explaining. Explain how carbon fixation became coupled to energy and reducing-power supply, while producing enough precursors to sustain the catalysts involved.
Hurdles
- H-CARB-1Carbon supplyThe problem. Every carbon atom in the cell comes from CO₂, which must be reduced before it can enter metabolism. In Aquifex this is done by the reverse Krebs cycle, whose carboxylating enzymes draw on low-potential electrons from ferredoxin.Why it is hard. CO₂ is a stable, fully oxidised molecule and is dilute in water. Reducing it needs a steady supply of strong reductant at the place where the products are used.Chemistry before lifeStage 1: Ingredients made under plausible early-Earth conditionsShown: CO₂ and simple carbon compounds are plentiful in volcanic and hydrothermal settings.In the books: 37 open problems on central carbon metabolism ↗
- H-CARB-2Catalysis and selectivityThe problem. The reverse Krebs cycle has about eleven steps, each catalysed by its own enzyme; the two carbon-fixing steps use iron–sulfur enzymes (pyruvate synthase and 2-oxoglutarate synthase).Why it is hard. Every step must win over competing side reactions. Metal ions speed up several of the steps, but they speed up unwanted reactions too, so the products drift away from the cycle.Molecular machinesStage 2: One step shown on its ownShown: Metal ions speed up several reverse Krebs cycle reactions without enzymes, but with limited selectivity (Muchowska et al. 2017).In the books: 37 open problems on central carbon metabolism ↗
- H-CARB-3Energy couplingThe problem. Several steps of the cycle run uphill: the carboxylations need reduced ferredoxin, and splitting citrate needs ATP. Energy has to be delivered to exactly those steps.Why it is hard. A favourable reaction elsewhere does not drive an unfavourable one unless something couples the two. In cells the coupling is done by the enzymes themselves.The integrated cellStage 0: Not yet addressed by experimentShown: not yet addressed by experiment.In the books: 37 open problems on central carbon metabolism ↗
- H-CARB-4Network closureThe problem. A cycle fixes carbon only if each turn regenerates its own starting molecule and returns more than it uses up.Why it is hard. If one step leaks or one intermediate decays, the cycle runs down and stops. Every step has to work, at sufficient rate, at the same time.The integrated cellStage 0: Not yet addressed by experimentShown: A self-renewing carbon cycle has not been shown without enzymes.In the books: 37 open problems on central carbon metabolism ↗
- H-CARB-5IntegrationThe problem. The cycle's products (acetyl-CoA, pyruvate, oxaloacetate, 2-oxoglutarate) are the starting points for amino acids, sugars, lipids, nucleotides and cofactors. Supply has to match what those pathways consume.Why it is hard. Carbon fixation is useful only when the pathways it feeds exist, and those pathways need the enzymes, cofactors and energy that the rest of the cell provides.The integrated cellStage 0: Not yet addressed by experimentShown: not yet addressed by experiment.In the books: 37 open problems on central carbon metabolism ↗
Scope. The modern pathways show what selected cells do today. They do not establish that the first living system used both routes, or required every modern enzyme at its beginning.
Experimental progress. A reconstructed biosynthetic network connects carbon assimilation with amino acid, nucleotide, and cofactor production. This provides a systems view of shared chemical inputs; a reconstruction is not an experimental demonstration of the first cell.
What would strengthen a natural account. Steps shown to work together under plausible early-Earth conditions, without a chemist choosing the reagents, purifying the products or changing conditions between steps, would strengthen a natural account of origins in proportion to what they explain. Loss of a claimed dependency or discovery of functional alternatives would weaken the corresponding design argument. Gaps in the record do not supply a numerical likelihood for either explanation.
Observations. Carbon fixation and precursor reactions supply amino-acid, lipid, nucleotide and cofactor pathways. Carbon-transfer and redox reactions require compatible cofactors and regeneration.
Hallmarks that apply.
- H24 Metabolic integration: Carbon fixation and precursor reactions supply amino-acid, lipid, nucleotide and cofactor pathways.
- H25 Cofactor dependency networks: Carbon-transfer and redox reactions require compatible cofactors and regeneration.
- H40 Cross-domain constraint satisfaction: Assimilation depends on usable energy, reducing equivalents and mineral resources.
The author’s conclusion. The coordinated features give the author a positive reason to consider design within the wider cellular architecture. For this local system alone, they do not establish that design is uniquely the best historical explanation. The conservative inference is that the system contributes to a cumulative design case, with its weight conditional on the comparative evidence and on how much plausible natural pathways explain.
From the book article Central Carbon Metabolism, with its scientific references.
How it was discovered
- 1937Hans Krebs and William Johnson describe the citric acid cycle, the hub of carbon metabolism (Nobel Prize 1953).Krebs & Johnson, Enzymologia 4:148–156 (1937)
- 1954Bassham, Benson and Calvin show how plants regenerate the molecule that captures CO₂, completing the Calvin cycle (Nobel Prize 1961).Bassham et al., Journal of the American Chemical Society 76:1760–1770 (1954)
- 1966Evans, Buchanan and Arnon propose that some bacteria run the citric acid cycle backwards to fix CO₂: the reductive TCA cycle that Aquifex uses.Evans, Buchanan & Arnon, PNAS 55:928–934 (1966)
- 2004Citryl-CoA lyase is discovered in a relative of Aquifex, showing that this group splits citrate in two steps instead of one.Aoshima, Ishii & Igarashi, Molecular Microbiology 52:763–770 (2004)
- 2014Braakman and Smith reconstruct the metabolic network of Aquifex aeolicus and use it to propose how carbon fixation first arose.Braakman & Smith, PLoS ONE 9:e87950 (2014)
- 2017Metal ions are shown to drive several consecutive reactions of the reverse Krebs cycle without enzymes.Muchowska, Varma & Moran, Nature Ecology & Evolution 1:1716–1721 (2017)
Each hurdle above is sorted by kind and by how far experiments have got (see “How hurdles are sorted” at the top).
All parts of the cell side by side: origins hub. The book articles:
- Central Carbon Metabolism: system page · full description · origins