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 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 complex carbon molecules in the form of sugars and oxidizes them to CO2 and water, the reverse cycle takes CO2 and water to make carbon compounds. This process is used by some bacteria to synthesise carbon compounds, sometimes using hydrogen, sulfide, or thiosulfate as electron donors.[1][2] In this process, it can be seen as an alternative to the fixation of inorganic carbon in the reductive pentose phosphate cycle which occurs in a wide variety of microbes and higher organisms.
In contrast to the oxidative citric acid cycle, the reverse or reductive cycle has a few key differences. One of the main differences is the conversion on succinate to 2-oxoglutarate. In the oxidative reaction this step is coupled to the reduction of NADH. However, the oxidation of 2-oxoglutarate to succinate is so energetically favourable, 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.[3]
The reaction is a possible candidate for prebiotic early-earth conditions and, so, is of interest in the research of the origin of life. It has been found that some non-consecutive steps of the cycle can be catalyzed by minerals through photochemistry,[4] while entire two and three-step sequences can be promoted by metal ions such as iron (as reducing agents) under acidic conditions. However, the conditions are extremely harsh and require 1 M hydrochloric or 1 M sulfuric acid and strong heating at 80–140 °C.
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