chemistry

Reverse Krebs cycle

Reverse Krebs cycle is a chemistry topic covered in the lgStudy science library. This page brings together a partial reference excerpt, illustrations, worked examples, real-world applications and a short study plan, so you can understand Reverse Krebs cycle rather than just read about it. In short: The reverse Krebs cycle (also known as the reverse tricarboxylic acid cycle, the reverse TCA cycle, or the reverse citric acid cycle, or the reductive tricarboxylic acid cycle, or the reductive TCA cycle) is a sequence of chemical reactions that are used by some bacteria and archaea to produce carbon compounds from carbon dioxide and water by the use of energy-rich reducing agents as electron donors. The reaction is…

Key takeaways

Reverse Krebs cycle belongs to chemistry; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect Reverse Krebs cycle to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of Reverse Krebs cycle from memory before moving on to harder problems.

Reference excerpt

The reverse Krebs cycle (also known as the reverse tricarboxylic acid cycle, the reverse TCA cycle, or the reverse citric acid cycle, or the reductive tricarboxylic acid cycle, or the reductive TCA cycle) is a sequence of chemical reactions that are used by some bacteria and archaea to produce carbon compounds from carbon dioxide and water by the use of energy-rich reducing agents as electron donors. The reaction is the citric acid cycle run in reverse. Where the Krebs cycle takes carbohydrates and oxidizes them to CO2 and water, the reverse cycle takes CO2 and H2O to make carbon compounds. This process is used by some bacteria (such as Aquificota) to synthesize carbon compounds, sometimes using hydrogen, sulfide, or thiosulfate as electron donors. This process can be seen as an alternative to the fixation of inorganic carbon in the Calvin cycle which occurs in a wide variety of microbes and higher organisms.

Differences from Krebs cycle In contrast to the oxidative citric acid cycle, the reverse or reductive cycle has a few key differences. There are three enzymes specific to the reductive citric acid cycle – citrate lyase, fumarate reductase, and α-ketoglutarate synthase. The splitting of citric acid to oxaloacetate and acetate is usually catalyzed by citrate lyase, rather than the reverse reaction of citrate synthase. The exceptions are Thermosulfidibacter takaii and Desulfurella acetivorans which truly run the synthase in reverse. Succinate dehydrogenase is replaced by fumarate reductase and α-ketoglutarate synthase replaces α-ketoglutarate dehydrogenase. The conversion of succinate to 2-oxoglutarate is also different. In the oxidative reaction this step is coupled to the reduction of NADH. However, the oxidation of 2-oxoglutarate to succinate is so energetically favorable, that NADH lacks the reductive power to drive the reverse reaction. In the rTCA cycle, this reaction has to use a reduced low potential ferredoxin – 2-oxoglutarate:ferredoxin oxidoreductase.

In nature Thiomicrospira denitrificans, "Candidatus Arcobacter", and Chlorobaculum tepidum have been shown to utilize the rTCA cycle to turn CO2 into carbon compounds. The ability of these bacteria, among others, to use the rTCA cycle, supports the idea that they are derived from an ancestral proteobacterium, and that other organisms using this cycle are much more abundant than previously believed. The rTCA of the chemolithotrophic Thermosulfidibacter takaii takes place via an "unexpected" reversal of citrate synthase. A kinetic network model has been built for this type of TCA. It contains the following enzymes:

rTCA proper: Citrate synthase (EC 2.3.3.1) Aconitate (EC 4.2.1.3) Isocitrate dehydrogenase (EC 1.1.1.42) 2-oxoglutarate:ferredoxin oxidoreductase (EC 1.2.7.3)Oxidative counterpart: 2-oxoglutarate dehydrogenase (EC 1.2.1.ak formerly 1.2.4.2) Succinate dehydrogenase (EC 1.3.5.1) Fumarate hydratase (EC 4.2.1.2) Malate dehydrogenase (EC 1.1.1.37) Pyruvate:ferredoxin oxidoreductase (EC 1.2.7.1)Oxidative counterpart: pyruvate dehydrogenase (EC 1.2.1.aj) Associated reactions, including anaplerotic: NADP-malic enzyme (EC 1.1.1.40) Phosphoenolpyruvate synthase (EC 2.7.9.2) Phosphoenolpyruvate carboxykinase (EC 4.1.1.49) Pyruvate kinase (EC 2.7.1.40) Pyruvate carboxylase (EC 6.4.1.1) Other reactions Ferredoxin—NAD reductase (EC 1.18.1.3) Ferredoxin—NADP reductase (EC 1.18.1.7) Adenylate kinase (EC 2.7.4.3) As with the standard Krebs cycle, there is a branching point between citrate and oxaloacetate going through acetyl-CoA and pyruvate, only reversed. The NADP-malic enzyme creates a second path from malate to pyruvate.

Variants Upon an influx of succinate, the rTCA model bifurcates into a partial reversal: it would perform succinate → fumarate → malate in the oxidative direction and the rest in the reductive direction (also ending in malate). This cycle runs at full speed and would reflect a chemolithomixotrophic lifestyle. A large input of acetyl-CoA would impair the rTCA by forcing the consumption of oxaloacetate to form citrate, causing bottlenecks of reduced flux. A smaller input would not cause the citrate synthase to run in the oxidative direction, but still hinders its action and reduces the flux. Overall this shows that a full rTCA cannot co-exist with a fully functional Wood–Ljungdahl (WL) pathway. As predicted, the following variants have been seen in deep-branching bacteria and archaea:

Incomplete rTCA, full WL (bacteria and archaea) Incomplete rTCA, full reverse glycolysis (rGly) (bacteria) Complete rTCA, incomplete WL or rGly (bacteria and archaea) Impaired but complete rTCA, full dicarboxylate/4-hydroxybutyrate pathway (DC/4HB) or a 3-hydroxypropionate/4-hydroxybutyrate pathway (3HP/4HB) (archaea). Full oxidiative TCA (oTCA) with incomplete DC/4HB (archaea). Full oTCA with Calvin cycle and incomplete rGly (bacteria). Incomplete oTCA with complete WL (bacteria).

Relevance to early life The reverse Krebs cycle is believed to be used by the first forms of life due to it matching a chemoautotrophic lifestyle. It is one of the most ancient carbon fixation pathways along with the Wood–Ljungdahl pathway (WL). It would have provided the building blocks for the earliest biomolecules. Its possible presence in the first forms of life and compatibility with prebiotic early-Earth conditions makes it of interest in the research of the origin of life. The question is thus split into three parts:

How would an abiotic (mineral) environment catalyze (at least some) steps of the cycle to form the earliest biomolecules? How would early biomolecules catalyze (at least some) steps of the cycle to propagate themselves? How would the last universal common ancestor perform (at least some) steps of the cycle using catalysts more similar to the enzymes of today?

… excerpt ends here. Continue reading the full article.

Illustrations

Worked examples

Example 1 — a first encounter with Reverse Krebs cycle

Start with the simplest possible case. Write down what Reverse Krebs cycle claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In chemistry, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Reverse Krebs cycle before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Reverse Krebs cycle ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Reverse Krebs cycle

In research: Reverse Krebs cycle appears in chemistry research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses Reverse Krebs cycle in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: Reverse Krebs cycle is common in secondary-school and first-year university syllabi. It links to neighbouring topics Biochemical reactions, Citric acid cycle, Metabolic pathways, so understanding it makes those chapters shorter.
In everyday life: Look for Reverse Krebs cycle outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

Affiliate

Preply — study more efficiently by working with a personal tutor. 50% off.

How to study Reverse Krebs cycle in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what Reverse Krebs cycle means in your own words.
Compare your version with the excerpt and mark what you missed.
Work through the three examples above with pen and paper.
Explain Reverse Krebs cycle out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is Reverse Krebs cycle in simple terms?

Why does Reverse Krebs cycle matter?

Because it connects several chemistry ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study Reverse Krebs cycle?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on Reverse Krebs cycle.