Home Products Cited in Publications Worldwide Reduction of NAD and NMN on mineral surfaces with H2 reveals a functional role for the AMP moiety in a prebiotic context
Henriques Pereira, Delfina P; Xie, Xiulan; Stewart, Sarah V; Subrati, Zainab; Beyazay, Tuğçe; Paczia, Nicole; Belz, Jürgen; Volz, Kerstin; Erastova, Valentina; Tüysüz, Harun
DOI:10.1038/s42004-025-01752-3 PMID:41168460
Many cofactors share a molecular structure – adenosine monophosphate (AMP) – that otherwise occurs in nucleic acids. The presence of AMP in cofactors has presented an evolutionary puzzle. Is it a biochemical ‘handle’ that allows proteins to bind the cofactor more tightly, or a relic from a prebiotic time when cofactors arose? Using the example of nicotinamide adenine dinucleotide (NAD), we find a previously unknown property of its AMP handle. Experiments with hydrogen gas on mineral surfaces show that the handle-free nicotinamide mononucleotide (NMN) overreduces quickly, while NAD gets reduced specifically. The handle allows NAD to function in a hydrothermal, mineral-based setting, indicating that it is a form of protection against a harsh environment. Our findings uncover a specific functional role for the AMP moiety of NAD under environmental conditions capable of non-enzymatic NAD reduction, thereby identifying a structural element of a redox cofactor that is older than the enzymes using it.

