User:Pacman118/Reverse Krebs cycle

The Reductive/Reverse TCA Cycle (rTCA cycle). Shown are all of the reactants, intermediates and products for this cycle.

Relevance to early life[edit]

The reaction is a possible candidate for prebiotic early-earth conditions and, therefore, 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, while entire two and three-step sequences can be promoted by metal ions such as iron (as reducing agents) under acidic conditions. In addition, these organisms that undergo photochemistry can and do utilize the citric acid cycle. However, the conditions are extremely harsh and require 1 M hydrochloric or 1 M sulfuric acid and strong heating at 80–140 °C.

Along with the these possibilities of the rTCA cycle contributing to early life and biomolecules, it is thought that the rTCA cycle could not have been completed without the use of enzymes. The kinetic and thermodynamic parameters of the reduction of highly oxidized species to push the rTCA cycle are seemingly unlikely without the necessary action of biological catalysts known as enzymes. The rate of some of the reactions in the rTCA cycle likely would have been too slow to contribute significantly to the formation of life on earth without enzymes. Considering the thermodynamics of the rTCA cycle, the increase in Gibb’s Free Energy going from product to reactant would make this cycle an unlikely feat without the help of enzymes.

Use of the Reverse Krebs Cycle [edit]

Thiomicrospira denitrificans and Candidatus Arcobacter have been shown to utilize the rTCA cycle to turn CO2 into a food source. The ability of these bacteria, among others, to use the rTCA cycle supports the idea that they're derived from an ancestral proteobacteria, and that other organisms using this cycle are much more abundant than previously believed.

Medical Relevance

The reverse Krebs cycle is proposed to be a major role in the pathophysiology of melanoma. Melanoma tumors are know to alter normal metabolic pathways in order to utilize waste products. These metabolic adaptations help the tumor adapt to its metabolic needs. The most well know adaptation is the Warburg effect where tumors increase their uptake and utilization of glucose. Glutamine is one of the known substances to be utilized in the reverse Krebs cycle in order to produce acetyl CoA. This type of mitochondrial activity could provide us with a new way to identify and target cancer causing cells.

Conclusion

The Reverse Krebs Cycle (also known as rTCA cycle) is a series of chemical processes that some bacteria use to create carbon compounds from CO₂ and H₂O. It is relevant due to it’s possible influence in the formation of early life and medical implications related to cancer studies.

References[edit]

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5. Ross, David S. (2007-02-01). "The Viability of a Nonenzymatic Reductive Citric Acid Cycle – Kinetics and Thermochemistry". Origins of Life and Evolution of Biospheres. 37 (1): 61–65. doi:10.1007/s11084-006-9017-6. ISSN 1573-0875.