Biochemistry & Organic Chemistry

Reduction Of NAD and NMN On Mineral Surfaces With H2 Reveals A Functional Role For The Adenosine Moiety In Prebiotic Evolution

By Keith Cowing

Status Report

Research Square

April 8, 2025

Filed under adenosine, AMP, biochemistry, biosignature, evolution, genomics, NAD, NMN, nucleic acid, prebiotic

Reduction Of NAD and NMN On Mineral Surfaces With H2 Reveals A Functional Role For The Adenosine Moiety In Prebiotic Evolution — Summarizing figure showing all educts and products detected during simultaneous reduction of NAD+ and NMN. NMN produces more side products than NAD, possibly creating a mechanistic bottleneck for the back reaction, for which only one-time reduced nicotinamides have a comparable reducing strength – both overreduction products such as NMNH3 and hydrolysis products such as NMNH2OH could likely not compete as reducing agents in a prebiotic scenario. Consequently, only single-reduced species such 1,4-NADH and 1,4-NMNH could be coupled for reduction reactions, thus detaching the reduction from a mineral surface. Based on assessments of the redox potential, we assume 1,6-NADH being able to reduce equally well as 1,4-NADH – not accounting for possible steric hindrances. — Research Square

Many cofactors share a molecular structure – adenosine – that otherwise occurs in nucleic acids. The presence of adenosine in cofactors has presented an evolutionary puzzle.

Is it a biochemical ‘handle’ that allows proteins to bind the cofactor more tightly, or is it a relic from a time when cofactors arose from the building blocks of genes? Using the example of nicotinamide adenine dinucleotide (NAD), we find a surprising and previously unknown property of its adenosine monophosphate (AMP) handle.

Reduction experiments with hydrogen gas (H₂) on mineral surfaces show that the handle-free nicotinamide mononucleotide (NMN) overreduces quickly, while NAD gets reduced specifically.

The AMP handle allows NAD to function in a hydrothermal, mineral-based setting, indicating that it is a form of protection against a harsh chemical environment in which biochemistry and life arose.

Our findings uncover a specific functional role for the AMP moiety of NAD under environmental conditions capable of nonenzymatic NAD reduction, thereby identifying a structural element of a redox cofactor that is older than the enzymes that use it.

Reduction of NAD and NMN on mineral surfaces with H2 reveals a functional role for the adenosine moiety in prebiotic evolution, Research Square (open access)

Astrobiology,

Keith Cowing

Explorers Club Fellow, ex-NASA Space Station Payload manager/space biologist, Away Teams, Journalist, Lapsed climber, Synaesthete, Na’Vi-Jedi-Freman-Buddhist-mix, ASL, Devon Island and Everest Base Camp veteran, (he/him)

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