title: The evolutionary portrait of metazoan NAD salvage.
abstract: 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.
authors.affiliation: IPATIMUP-Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal.
authors.forename: João
authors.initials: J
authors.lastname: Carneiro
authors.forename: Sara
authors.initials: S
authors.lastname: Duarte-Pereira
authors.forename: Luísa
authors.initials: L
authors.lastname: Azevedo
authors.forename: L Filipe C
authors.initials: LF
authors.lastname: Castro
authors.forename: Paulo
authors.initials: P
authors.lastname: Aguiar
authors.forename: Irina S
authors.initials: IS
authors.lastname: Moreira
authors.forename: António
authors.initials: A
authors.lastname: Amorim
authors.forename: Raquel M
authors.initials: RM
authors.lastname: Silva
mesh_terms: D020816:Amino Acid Motifs / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D053898:Biosynthetic Pathways / Q000235:genetics*; D017124:Conserved Sequence / Q000235:genetics; D019143:Evolution, Molecular; D006801:Humans; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D007448:Invertebrates / Q000201:enzymology; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D009243:NAD / Q000378:metabolism*; D009535:Nicotinamidase / Q000737:chemistry; D054409:Nicotinamide Phosphoribosyltransferase / Q000737:chemistry; D010802:Phylogeny; D017433:Protein Structure, Secondary; D017386:Sequence Homology, Amino Acid; D040681:Structural Homology, Protein
chemical_list: D009243:NAD; D054409:Nicotinamide Phosphoribosyltransferase; D009535:Nicotinamidase