The dawn of life: NMR has (some of) the details

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  • Published: Jan 15, 2018
  • Author: David Bradley
  • Channels: NMR Knowledge Base
thumbnail image: The dawn of life: NMR has (some of) the details

Life pioneers

Ramanarayanan Krishnamurthy, PhD, associate professor of chemistry at TSRI and senior author of the new study Credit: Faith Hark/The Scripps Research Institute

Nuclear magnetic resonance (NMR) spectroscopy and other techniques have been used to study the linked cycles of oxidative decarboxylation of glyoxylate. Such cycles could be perceived as being proto-metabolic analogues of the citric acid cycle on which life depends and might provide a new clue as to how life on earth emerged from the primordial soup.

British chemist Leslie Orgel, a pioneer in the field of origins of life research pointed out that, "If complex cycles analogous to metabolic cycles could have operated on the primitive Earth before the appearance of enzymes or other informational polymers, many of the obstacles to the construction of a plausible scenario for the origin of life would disappear." Now, Ramanarayanan Krishnamurthy of The Scripps Research Institute, together with Jayasudhan Reddy Yerabolu of The Scripps Research Institute and the National Science Foundation (NSF)/National Aeronautics and Space Administration (NASA) Center for Chemical Evolution; and Julia Nelson and Chandler Joel Rhea of Furman University have taken that concept to heart. They have developed a fascinating new theory as to how life on Earth may have begun based on a picture of protometabolic cycles. The researchers describe the details in the journal Nature Communications and demonstrate that key chemical reactions that support life today may well have been carried out with ingredients likely present on the planet four billion years ago.

"This was a black box for us," explain Krishnamurthy. "But if you focus on the chemistry, the questions of origins of life become less daunting," he suggests. In the new work, the researchers focused on a series of chemical reactions that make up the citric acid cycle. The citric acid cycle is also known as the tricarboxylic acid (TCA) cycle or the Krebs cycle. It is essentially a sequence of chemical reactions used by all aerobic organisms to release the chemical energy stored in carbohydrates, fats, and proteins through the release of acetyl-coenzyme A from those source and to generate adenosine triphosphate (ATP) and waste carbon dioxide. All aerobic organisms rely on the citric acid cycle to stay alive.

Energy cycle

In earlier models of the biochemistry of the earliest forms of life, researchers had suggested that the same molecules for the citric acid cycle used by life today would have been used all those hundreds of millions of years ago. However, as Krishnamurthy explains, those molecules are quite fragile and it is more than likely that the chemical reactions of the modern citric acid cycle could not have occurred because the starting materials simply did not yet exist.

To solve this problem, the team looked at the requisite chemical reactions first and worked backwards to find starting materials that could have existed on the prebiotic earth. They homed in on two non-biological reaction cycles, the HKG (alpha-hydroxy-gamma-ketoglutarate) cycle and the malonate cycle and reasoned that these two systems may have come together to form a prototype of the citric acid cycle. The two cycles involve reactions that perform the same fundamental chemistry as alpha-ketoacids and the beta-ketoacids in the citric acid cycle. The team explains that the shared reactions include aldol additions, which can act as a new source for the starting materials of the cycles, and also beta and oxidative decarboxylations, which release carbon dioxide.

The ultimate starting materials

Intriguingly, these reactions also revealed themselves to be able to synthesize certain amino acids as well as carbon dioxide. Those amino acids are also end products of the citric acid cycle. Ultimately, the emergence of catalysts, in the form of biological enzymes, would have nudged the systems along a different route as efficiency and energetic took hold leading to the displacement of the non-biological molecules in the fundamental reactions with their "biological" counterparts.

"The chemistry could have stayed the same over time, it was just the nature of the molecules that changed," explains Krishnamurthy. "The molecules evolved to be more complicated over time based on what biology needed." Furman University's Greg Springsteen, first author on the paper adds that, "Modern metabolism has a precursor, a template, that was non-biological." The plausibility of this hypothesis is bolstered by glyoxylate at the centre of these reactions. This molecule would have been present on the early Earth and remains a component of the citric acid cycle to this day.

Related Links

Nature Commun 2018, online: "Linked cycles of oxidative decarboxylation of glyoxylate as protometabolic analogs of the citric acid cycle"

Article by David Bradley

The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.

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