Tag Archives: Krebs cycle

A role for iron in the origin of life

Experiments aimed at suggesting how RNA and DNA – prerequisites for life, reproduction and evolution – might have formed from a ‘primordial soup’ have made slow progress. Another approach to the origin of life is investigation of the most basic chemical reactions that it engages in. Whatever the life form, prokaryote or eukaryote, its core processes involve reducing carbon dioxide, or other simple carbon-bearing compounds, and water to synthesise organic molecules that make up cell matter. Organisms also engage in metabolising biological compounds to generate energy. At their root, these two processes mirror each other; a creative network of reactions and another that breaks compounds down, known as the Krebs- and the reverse-Krebs cycles. In living organisms both are facilitated by other organic compounds that, of course, are themselves produced by cells. How such networks arose under inorganic conditions remains unknown, but three biochemists at the University of Strasbourg in France (Muchowska, K.B. et al. 2019. Synthesis and breakdown of universal metabolic precursors promoted by iron. Nature, v. 569, p. 104-107;  DOI: 10.1038/s41586-019-1151-1) have designed an inorganic experiment. They aimed to investigate how two simple organic compounds, which conceivably could have formed in a lifeless early environment, might have been encouraged to kick-start basic living processes. These are glyoxylate (HCOCO2) and pyruvate (CH3COCO2).

The most difficult chemical step in building complex organic compounds is inducing carbon atoms to bond together through C-C bonds; a process that thermodynamics tends to thwart but is accomplished in living cells by adenosine tri-phosphate (ATP). Previous workers focussed on interactions between reactive compounds, such as cyanide and formaldehyde, as candidates for the precursors of life, but such chemistry is totally different from what actually goes on in organisms. Joseph Moran, one of the co-authors of the paper, and his research group recently settled on five fundamental linkages of C, H and O as ‘universal hubs’ at the core of the Krebs cycle and its reverse. Kamila Muchowska and co-workers found that glyoxylate and pyruvate introduced into a simulated hydrothermal fluid that contains ions of ferrous iron (reduced Fe2+) were able to combine in producing all five ‘universal hubs. Ferrous iron clearly acted as a catalyst, through being a powerful reducing agent or electron donor, to get around the stringencies of classic thermodynamics. Moran’s team had previously shown that pyruvate itself can form inorganically from CO2 in water laced with iron, cobalt and nickel ions. Formation of glyoxylate in such a manner has yet to be demonstrated. Nevertheless, the two together in a watery soup of transition metal ions seem destined to produce an abundance of exactly the compounds at the root of living processes. In fact the experiment showed that all but two of the eleven components of the Krebs cycle can be synthesised inorganically.


Metal-rich ‘black smoker’ at a hydrothermal vent on the mid-Atlantic ridge(credit: Kate Larkin, Seascape, Belgium)

Until the rise of free oxygen in the Earth system some 2400 Ma ago, the oceans would have been awash with soluble ferrous iron. This would have been especially the case around hydrothermal vents that result from the interaction between water and hot mafic lavas of the oceanic crust, together with less abundant transition-metal ions, such as those of nickel and cobalt. The ocean-vent hypothesis for the origin of life seems set for a surge forward.

See also: Katsnelson, A. 2019. Iron can catalyse metabolic reactions without enzymes.

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