Nicotinamide Coenzyme Synthesis: A Case of Ribonucleotide Emergence or a Byproduct of the RNA World?



Coenzymes likely represent the oldest metabolic fossils within a cell, as suggested by their presence and essentiality in all kingdoms of life and the autocatalytic nature of their biosynthetic pathways. The presence of a ribonucleotidyl group in the structure of most coenzymes that use it as a “handle” for binding to the protein catalyst means that ribonucleotides must have been present at the time coenzymes emerged. An open question remains whether the ribonucleotidyl group has been co-opted from a preexisting RNA in a primordial “RNA world” before the emergence of proteins, or it represents the evolutionary predecessor of contemporary nucleic acids. The nicotinamide coenzyme NAD (P) is one of the oldest molecules, not only in the history of biochemistry, but also in the evolutionary steps towards the emergence of life. Together with relatively simple organics, such as PRPP (5′-phosphoribosyl 1′-pyrophosphate), PLP (pyridoxal 5′-phosphate) and many others, it may have been a crucial prebiotic agent in organizing a collectively autocatalytic protometabolic ecosystem. Here, the NAD(P) biosynthetic pathway will be described with views on its origin. NAD(P)’s peculiar biochemical features will also be discussed with the aim to offer novel arguments to the debate on the sequence of chemical evolution in the origin of life.



flavin adenine dinucleotide


flavin mononucleotide


nicotinamide adenine dinucleotide


nicotinate mononucleotide


nicotinamide mononucleotide






5′-phosphoribosyl 1′-pyrophosphate

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© Springer-Verlag Berlin Heidelberg 2011

Authors and Affiliations

  1. 1.Section of Biochemistry, Department of Molecular Pathology and Innovative TherapiesUniversità Politecnica delle MarcheAnconaItaly

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