Investigating the Origins of Metabolism - - Chromatography Online
Investigating the Origins of Metabolism

The Column
Volume 10, Issue 9, pp. 8

Scientists at the University of Cambridge (Cambridge, UK) have reconstructed the early conditions of the Earth’s oceans to find that spontaneous chemical reactions could have generated the first biological molecules, before the evolution of organisms or the existence of enzymes.1 The study published in the journal Molecular Systems Biology presents data collected from liquid chromatography–triple quadrupole mass spectrometry (LC–QTOF‑MS) suggesting that reactions central to our core metabolism could have spontaneously occurred.

Life in its primitive form is widely thought to have begun around 4 billion years ago on Earth. At this time, the oceans are believed to have been iron-rich. As to how it began, there are a number of theories. One of the most prominent and well-known is that of Miller and Urey in 1953 who demonstrated that amino acids could be created by applying an electrical charge to a “primordial soup” of hydrogen, methane, water, and ammonia. The hypothesis that the amino acids spontaneously formed could be lthe basis of enzymatic proteins required for metabolism.

Core metabolic processes are essential to life, and are responsible for the production of energy, lipids, proteins, and more. The reactions involved within the metabolism network are largely conserved across all organisms, suggesting a single origin from which the network has evolved. Core metabolism has been thought to have come after the formation of proteins as enzymes are key to many metabolic reactions.

The team reconstructed conditions of the Archean Ocean (4 billion years ago) based on the sediment composition proposed by the literature. Metabolites key to central metabolism (including glucose-6-phosphate [G6P], fructose-6-phosphate [F6P], and fructose 1,6-bisphosphate [F16BP]) were incubated at 50–90 ºC in water, the temperature of water around the hydrothermal vents of oceanic volcanoes. The resulting compounds were analyzed using LC–QTOF‑MS. The team was able to observe almost 29 spontaneous reactions, including the formation and interconversion of glucose, pyruvate, the amino acid precursor erythrose-4-phophate, and the nucleic acid precursor ribose-5-phosphate. By using single reaction monitoring mode for the analysis, the team were able to determine absolute quantities for 15 intermediates.

Markus Ralser of the University of Cambridge and the National Institute for Medical Research said: “Our results show that reaction sequences that resemble two essential reaction cascades of metabolism, glycolysis and the pentose-phosphate pathways, could have occurred spontaneously in the earth’s ancient oceans.” He added: “In our reconstructed version of the ancient Archean ocean, these metabolic reactions were particularly sensitive to the presence of ferrous iron, which was abundant in the early oceans, and accelerated many of the chemical reactions that we observe. We were surprised by how specific these reactions were.”

The paper demonstrates the possibility that the iron-rich oceans could have been sufficient to catalyze the beginning of core metabolism, without the presence of enzymes. It also suggests that RNA molecules could have been formed from a basic mix of sugar metabolites. However, the origin of the sugar metabolites is still in question and the chance that a small solution of metabolites in an ocean could trigger the beginnings of life is questionable. &mdash B.D.

1. M.A. Keller, A.V. Turchyn, and M. Ralser, Molecular Systems Biology DOI 10.1002/msb.20145228 (2014).


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