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From microbes to cancer: how does the reverse Krebs cycle change our understanding of metabolism?
In the world of biochemistry, the Krebs cycle is the core of energy production, but as scientists deepen their research, they find that the reverse Krebs cycle (rTCA) plays an important role in life. Its origin and importance in cancer metabolism are also gradually emerging. This metabolic pathway is not only widespread in microorganisms, but may also play a key role in explaining the basic metabolic processes of certain cancers.
The reverse Krebs cycle is a series of chemical reactions that certain bacteria and archaea use to synthesize carbon compounds from carbon dioxide and water.
Basic operation of the reverse Krebs cycle
The basic principle of the reverse Krebs cycle is that this process is actually the reverse execution of the Krebs cycle. In contrast to the conventional Krebs cycle, it uses electron donors such as hydrogen, sulfides or sulfates to convert carbon dioxide and water into carbon compounds. This process is used by some bacteria (e.g. Aquificota) and is in contrast to the more widespread Calvin cycle. In chemical reactions, the reverse Krebs cycle differs from the traditional Krebs cycle in several significant ways. These differences are mainly reflected in the use of specific enzymes such as citrate lyase, fumarate reductase and α-ketoglutarate synthase. These enzymes play a central role in the reverse Krebs cycle, allowing the entire process to proceed efficiently.Compared with the traditional Krebs cycle, the reverse Krebs cycle uses different main enzymes, which leads to fundamental differences in the chemical reaction pathways of the two.
Links to early life
The uniqueness of the reverse Krebs cycle has attracted great attention from scientists, especially in the study of the origin of life. The study suggests that this cycle could be a candidate pathway for the generation of life under prebiotic conditions on early Earth. Under some extreme circumstances, certain reaction steps can be catalyzed by minerals. This means that the reverse Krebs cycle is not limited to present-day organisms, but may have played an important role in the early evolution of life on Earth. Scientists have noted that in certain acidic environments, metal ions such as iron may act as reducing agents, speeding up the reaction, raising the possibility of the reverse Krebs cycle as a chemical reaction in early life. These findings not only challenge our traditional views on the origin of life, but also suggest a new role for the reverse Krebs cycle in metabolic evolution.The catalytic reactions of the reverse Krebs cycle likely require the help of enzymes because without them, the rates of some reactions would be too slow to significantly contribute to the formation of life.
Relationship between reverse Krebs cycle and cancer
As research progresses, we find that the role of the reverse Krebs cycle is not limited to microorganisms, but also has a profound impact on medical research. The reverse Krebs cycle is considered an important player in the pathophysiology of cancers such as melanoma. Tumor cells alter normal metabolic pathways to accommodate their unique metabolic needs, and the reverse Krebs cycle provides a way to utilize waste products, thereby aiding tumor growth. For example, cancer cells often use glutamate to produce acetyl-CoA via reverse Krebs cycle metabolism. This mitochondrial activity not only shows the adaptability of cancer cells, but also provides us with new ways to identify and attack cancer cells.Using metabolic adaptation in the reverse Krebs cycle, we may be able to find new means to target cancer, which will have revolutionary significance for the future of cancer treatment.
How microorganisms use the reverse Krebs cycle
Another aspect of interest is the ability of many microorganisms to convert CO2 into carbon compounds using the reverse Krebs cycle. Studies have shown that bacteria such as Thiomicrospira denitrificans, Candidatus Arcobacter and Chlorobaculum tepidum are able to carry out this process, which also supports the view that these organisms originated from early proteobacteria. The presence of these bacteria suggests that organisms that use the reverse Krebs cycle are more common than previously thought. This is of great significance for our in-depth understanding of the composition and evolution of microbial ecosystems.The microbial exploitation of the reverse Krebs cycle reminds us that there are a large number of undiscovered metabolic pathways hidden in nature that may change our basic understanding of metabolism.
In studying the reverse Krebs cycle, we not only see the origin of life, but also understand how cancer uses nature's chemical reactions to promote its growth. As science continues to advance, this field will continue to reveal the mysteries of life and health. Can we discover more key clues about the origin of life through more in-depth research?
