NAD⁺ biosynthesis and salvage – a phylogenetic perspective

Abstract

NAD is best known as an electron carrier and a cosubstrate of various redox reactions. However, over the past 20 years, NAD + has been shown to be a key signaling molecule that mediates post-translational protein modifications and serves as precursor of ADP-ribose-containing messenger molecules, which are involved in calcium mobilization. In contrast to its role as a redox carrier, NAD + -dependent signaling processes involve the release of nicotinamide (Nam) and require constant replenishment of cellular NAD + pools. So far, very little is known about the evolution of NAD(P) synthesis in eukaryotes. In the present study, genes involved in NAD(P) metabolism in 45 species were identified and analyzed with regard to similarities and differences in NAD(P) synthesis. The results show that the Preiss-Handler pathway and NAD + kinase are present in all organisms investigated, and thus seem to be ancestral routes. Additionally, two pathways exist that convert Nam to NAD + ; we identified several species that have apparently functional copies of both biosynthetic routes, which have been thought to be mutually exclusive. Furthermore, our findings suggest the parallel phylogenetic appearance of Nam N-methyltransferase, Nam phosphoribosyl transferase, and poly-ADP-ribosyltransferases.

Nicotinate O-Glucosylation Is an Evolutionarily Metabolic Trait Important for Seed Germination under Stress Conditions in Arabidopsis thaliana

“…NAD + and its derivatives (e.g., NADH, NADP + , and NADPH) are essential cofactors for many of the more than 1800 redox reactions that widely occur across all kingdoms of life (Gossmann et al, 2012). Common redox reactions do not generally lead to net consumption of NAD [we use the term NAD to represent NAD(P)(H) hereafter].…”

A Key Enzyme of the NAD + Salvage Pathway in Thermus thermophilus: Characterization of Nicotinamidase and the Impact of Its Gene Deletion at High Temperatures

“…T. elongates possesses a gene encoding a putative nicotinate phosphoribosyltransferase (NaPRT), which is involved in the salvage synthesis of NAD ϩ and therefore may have an alternative route to supply nicotinate to the salvage pathway. By contrast, genes involved in NAD ϩ salvage synthesis are not found in thermophilic methanogenic archaea M. thermoautotrophicum and M. jannaschii (2,6). These facts indicate that the NAD ϩ salvage pathway is not necessarily conserved among all thermophiles.…”

“…For example, the growth of Escherichia coli was severely suppressed under limited availability of intracellular NAD ϩ (21). Many organisms possess distinct types of pathways for the salvage synthesis of NAD ϩ , in which chemical and/or enzymatic degradants of NAD ϩ (e.g., nicotinamide and nicotinate) can be directly utilized as building blocks of the cofactor resynthesis (2,6). Some nicotinate-auxotrophic yeasts (22) and pathogenic microorganisms (23)(24)(25) are known to grow even without a de novo synthetic pathway for NAD ϩ , indicating the importance of the salvage pathway in these organisms.…”

Thermococcus kodakarensis : the key to affordable biohydrogen production

“…[148,155,160,161]. In the de novo pathway, NAD + is generated from quinolinic acid, which in prokaryotes is produced from either L-aspartate or L-tryptophan [159,162,163].…”

“…In the NAD + synthesis pathways, several variations exist and multiple enzymes are involved [161,164]. In contrast, NADK is the sole enzyme able to generate NADP + de novo.…”