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New Clues to Chemical Origins of Metabolism at Dawn of Life
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origins of life
New Clues to Chemical Origins of Metabolism at Dawn of Life
By
John Rennie
October 12, 2020
The ingredients for reactions ancestral to metabolism could have formed very easily in the primordial soup, new work suggests.
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On the early Earth, a forerunner of the complex cycle of reactions that underpins metabolism in today’s cells might have originated from interactions between just two simple, versatile molecules in water, according to new research.
Glenn Harvey for Quanta Magazine
Introduction
By John Rennie
Deputy Editor
October 12, 2020
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biochemistry
biology
cells
energy
metabolism
origins of life
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Popular speculations about how life evolved out of a soup of chemicals on the early Earth often focus on the origins of DNA and RNA, the molecules of genetic information. But the genesis of genes is only one of the mysteries that origin-of-life theories must reckon with. Another is the rise of metabolism — the biochemical processes inside cells that make life possible by continuously drawing energy from the environment and directing it into the assembly of vital molecules. It’s a complex problem on which there has been little headway.
But scientists may have just turned an important corner in that search. Today in Nature Chemistry, researchers at Furman University and the Scripps Research Institute announced a discovery about how one of the most important parts of cellular metabolism might have come to be. The researchers showed that, elaborate as that chemical mechanism is in cells today, nearly all the ingredients for a potential forerunner to it could have formed easily from just two simple organic compounds reacting in water.
Other scientists hailed the significance of the new findings, as well as the originality and rigorous chemical expertise of the researchers.
Greg Springsteen of Furman University said that in the approach to this origins-of-metabolism study that he and his colleagues took, “We were following rather than leading the chemistry.”
Jeremy Fleming/Furman University
A central pillar of all cellular metabolism — and the bane of generations of high school biology students who had to memorize it — is a complex 10-step chemical process variously known as the tricarboxylic acid (TCA) cycle, the citric acid cycle or the Krebs cycle. “The TCA cycle is at the heart of much of modern biology, where it is used both to break down food into energy and to synthesize vital building blocks of proteins,” said Greg Springsteen, a professor of chemistry at Furman University, an origins-of-life researcher and one of the authors of the new study. Anaerobic organisms can also run the cycle in reverse to transform carbon dioxide into the organic building blocks of fats and sugars.
Because the TCA cycle feeds into so many vital processes in even the simplest cells, scientists suspect it was one of the early reactions to establish itself in the prebiotic soup. To reconstruct how it evolved, biochemists have generally tried to work backward by replacing the eight enzymes involved in the modern TCA cycle with transition metals, since those can act as catalysts for many reactions and should have been abundant. But the transition metals often failed to produce the desired intermediary molecules, or catalyzed their breakdown as fast as they made them, and the metals typically needed high temperatures or other extreme conditions to work. “Metals and harsh conditions can be good [at] accelerating the reactions yet also [promote] the destruction of the products,” said Juli Peretó, a professor of biochemistry and molecular biology at the University of Valencia in Spain. “This situation makes rather implausible or unrealistic some of the proposed schemes.”
To the origins-of-life researcher Ramanarayanan Krishnamurthy, an associate professor of chemistry at the Scripps Research Institute and another co-author of the new paper, this was “a classic case of how the focus solely on biological clues has led this community into a corner, which has stymied real progress in the field.”
Following the Chemistry
Krishnamurthy, Springsteen and their colleagues took a completely different approach. Instead of trying to find the precursor to the TCA cycle by swapping in simpler versions of its components, they...