The evolutionary portrait of metazoan NAD salvage

João Carneiro, Sara Duarte-Pereira, Luísa Azevedo, L. Filipe C. Castro, Paulo Aguiar, Irina S. Moreira, António Amorim, Raquel M. Silva

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)


Nicotinamide Adenine Dinucleotide (NAD) levels are essential for cellular homeostasis and survival. Main sources of intracellular NAD are the salvage pathways from nicotinamide, where Nicotinamide phosphoribosyltransferases (NAMPTs) and Nicotinamidases (PNCs) have a key role. NAMPTs and PNCs are important in aging, infection and disease conditions such as diabetes and cancer. These enzymes have been considered redundant since either one or the other exists in each individual genome. The co-occurrence of NAMPT and PNC was only recently detected in invertebrates though no structural or functional characterization exists for them. Here, using expression and evolutionary analysis combined with homology modeling and protein-ligand docking, we show that both genes are expressed simultaneously in key species of major invertebrate branches and emphasize sequence and structural conservation patterns in metazoan NAMPT and PNC homologues. The results anticipate that NAMPTs and PNCs are simultaneously active, raising the possibility that NAD salvage pathways are not redundant as both are maintained to fulfill the requirement for NAD production in some species.
Original languageEnglish
Article numbere64674
JournalPLoS ONE
Issue number5
Publication statusPublished - 28 May 2013
Externally publishedYes


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