- Scientists have discovered that a version of the Krebs cycle, the heart of cellular metabolism, can take place without the proteins known as enzymes.
- While scientists have shown that this cycle runs in the oxidative direction outside of cells, they have yet to reproduce the reductive Krebs cycle that is present in some ancient bacteria.
Scientists have discovered that a version of the Krebs cycle, the heart of the cellular metabolic network, can take place without the cellular proteins known as enzymes. Since the Krebs cycle does not require cellular proteins to occur, researchers now believe that metabolism may predate life. In fact, spontaneous chemical reactions may have served as the foundation for life on Earth.
“Metabolism” describes the web of chemical reactions that maintain the living state of cells and organisms. This includes both reactions that synthesize amino acids and lipids that cells need and reactions that break down molecules to generate energy. Cells use lipids and amino acids in membranes and proteins and to create the molecules that are consumed to generate energy.
The intriguing question scientists now face is this: how did this complex cycle evolve at all if it predated life?
Questions About Life’s Origins
Two main theories about the evolution of the Krebs cycle have been proposed. One says that RNA came first, prompting the evolution of the Krebs cycle. However, not only is RNA made from metabolic products, evolutionary principles suggest that the reactions must have predated life; existing in the first life forms immediately, these chemical reactions offered some kind of advantage, a selective pressure which eventually resulted in the evolution of enzymes.
The other theory is that some form of the Krebs cycle existed before life forms did, and was then adopted by living cells. The cycle then evolved inside and with life forms, developing enzymes to become more efficient. This theory was dismissed by many in the past, but these latest findings published in Nature Ecology & Evolution lend it credence.
The research team exposed Krebs cycle chemicals to chemicals that would have been present in the sediments of early oceans. Eventually they triggered 24 chemical reactions in sequence — something very similar to today’s Krebs cycle. Thus far, however, they have only shown that this cycle runs in the oxidative direction, a development that would have taken place only once there was molecular oxygen in Earth’s atmosphere. They have yet to generate the reductive Krebs cycle that is still present in some ancient bacteria.
The researchers point out that there are still key components of life that this work does not explain, said Mark Ralser of the Francis Crick Institute in London, leader of the team who reported the findings.
“With the metabolic pathway alone, you have a very good starting point for life, but it is not life, just a chemical-reaction network,” Ralser said in an interview with New Scientist. “You also need things like membranes to contain the reactions, and the genetic machinery that enables inheritance.”
“How do you bring these elements together in one environment and in non-extreme conditions, and make them work?” Ralser asked. “This is still a big challenge.”