Role of geochemical protoenzymes (geozymes) in primordial metabolism: specific abiotic hydride transfer by metals to the biological redox cofactor NAD(+)

Hydrogen gas, H(2), is generated in serpentinizing hydrothermal systems, where it has supplied electrons and energy for microbial communities since there was liquid water on Earth. In modern metabolism, H(2) is converted by hydrogenases into organically bound hydrides (H(–)), for example, the cofactor NADH. It transfers hydrides among molecules, serving as an activated and biologically harnessed form of H(2). In serpentinizing systems, minerals can also bind hydrides and could, in principle, have acted as inorganic hydride donors—possibly as a geochemical protoenzyme, a ‘geozyme’— at the origin of metabolism. To test this idea, we investigated the ability of H(2) to reduce NAD(+) in the presence of iron (Fe), cobalt (Co) and nickel (Ni), metals that occur in serpentinizing systems. In the presence of H(2), all three metals specifically reduce NAD(+) to the biologically relevant form, 1,4‐NADH, with up to 100% conversion rates within a few hours under alkaline aqueous conditions at 40 °C. Using Henry's law, the partial pressure of H(2) in our reactions corresponds to 3.6 mm, a concentration observed in many modern serpentinizing systems. While the reduction of NAD(+) by Ni is strictly H(2)‐dependent, experiments in heavy water ((2)H(2)O) indicate that native Fe can reduce NAD(+) both with and without H(2). The results establish a mechanistic connection between abiotic and biotic hydride donors, indicating that geochemically catalysed, H(2)‐dependent NAD(+) reduction could have preceded the hydrogenase‐dependent reaction in evolution.