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ORAL COMMUNCATION 01
An evolutionary perspective on metazoan NAD salvage pathways
João Carneiro 1,2 , Sara Duarte-Pereira 1 , Luísa Azevedo 1,2 , L. Filipe C. Castro 3 , Paulo Aguiar 4 ,
Irina S. Moreira 5 , António Amorim 1,2 and Raquel M. Silva 1
1 IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto; 2 Faculty of
Sciences of the University of Porto; 3 Interdisciplinary Centre for Marine and Environmental Research
(CIIMAR), CIMAR Associate Laboratory, University of Porto; 4 CMUP - Centro de Matemática da
Universidade do Porto; 5 REQUIMTE - Rede de Química e Tecnologia, Faculty of Sciences, University of
Porto
Nicotinamide Adenine Dinucleotide (NAD) is a cofactor in redox reactions and a substrate
for NAD-consuming enzymes, such as PARPs and sirtuins. The maintenance of NAD levels is
crucial, thus, organisms use distinct pathways for NAD production and salvage depending
on alternative precursors.
NAD salvage enzymes have gained increased attention due to their roles in aging, infection
and disease and, more recently, as therapeutic targets in cancer [1]. Nicotinamide
phosphoribosyltransferase (NAMPT) and Nicotinamidase (PNC) are the functional
homologues in different NAD salvage pathways and, until now, NAMPT was thought to be
restricted to vertebrates and both NAMPT and PNC homologues had not been found in the
same lineages.
By combining molecular and structural biology with comparative and evolutionary
approaches, we provide, for the first time, experimental evidence that both enzymes are
expressed simultaneously in invertebrate species, identify active site residues of
invertebrate enzymes and emphasize sequence and structural conservation patterns in
metazoan NAMPTs and PNCs. The results indicate that both NAMPTs and PNCs can be
concurrently functional in the same species, which indicates that these enzymes are not
redundant after all [2].
[1] Chiarugi A, et al. The NAD metabolome - a key determinant of cancer cell biology. Nat Rev Cancer,
12:741-52 (2012).
[2] Carneiro J, et al. The Evolutionary Portrait of Metazoan NAD Salvage. PLoS ONE. Accepted (2013).
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