ABSTRACT Metabolism is a critical process for biology and is of great interest to those researching geobiological processes and the origins of life. A metabolism comprises a network of chemical reactions for molecular synthesis, energy conversion pathways, and cellular function. Understanding the mechanisms underlying metabolic processes provides insight into the evolution of electrochemical processes in complex systems and informs the possible pathways by which abiotic chemistry transitioned to biochemistry. Modern enzymes utilize cofactors to mediate chemical reactions and overcome energetic limitations. While enzymes are specific, large, and complex biological proteins, cofactors are simpler ions and molecules incorporated within the larger protein complex. Cofactors play a fundamental role in supplementing an enzyme's catalytic role and may represent a convergence between abiotic and biotic chemistry, allowing studies of cofactors to reveal potential prebiotic processes. Here, we review some of the organic / nucleotide cofactors participating in the electron transport chain (ETC): their structures, capacity for energy conversion, and their putative role in the origins of life. We choose to focus on four specific organic cofactors that have evolved to be key in extant mitochondrial ETCs—adenosine triphosphate (ATP), nicotinamide adenine dinucleotide (NADH), flavins (FAD, FMN), and quinones (ubiquinone)—to conceptually bridge the gap between the earliest inorganic cofactors and the protein complexes of modern biochemistry. We then make recommendations for future research topics and avenues.
Riazi‐Sekowski et al. (2026) studied this question.