Nicotinamide adenine dinucleotide biosynthetic enzymes (NBE)

Nicotinamide adenine dinucleotide (NAD+) biosynthetic enzymes are a group of proteins that maintain the cellular pool of NAD+, a coenzyme essential for redox reactions and a substrate for enzymes like sirtuins and poly(ADP-ribose) polymerases (PARPs) (Columbia University, 2021; NIH, 2020). These enzymes function across three main pathways: the de novo pathway from tryptophan (e.g., IDO1, TDO, QPRT), the Preiss-Handler pathway from nicotinic acid (e.g., NAPRT), and the salvage pathways from nicotinamide (e.g., NAMPT) and nicotinamide riboside (e.g., NRK) (Goldman Laboratories, 2024; NIH, 2018). They play a critical role in regulating energy metabolism, DNA repair, and cellular signaling (NIH, 2020). In oncology, inhibitors of NAMPT and IDO1 are used to deplete NAD+ levels, thereby inducing metabolic collapse and cell death in tumors that are highly dependent on these pathways (ResearchGate, 2021; Semantic Scholar, 2020). Conversely, in the context of aging and neurodegeneration, where NAD+ levels naturally decline, therapeutic strategies involve the use of NAD+ precursors like NMN and NR to replenish these levels and improve mitochondrial function (NIH, 2018; NIH, 2021). However, targeting these enzymes presents challenges, including dose-limiting toxicities such as thrombocytopenia and the potential risk of promoting tumor growth when augmenting NAD+ levels (ResearchGate, 2021; NIH, 2021). The complexity of NAD+ metabolism requires a nuanced approach to drug development, balancing the need for NAD+ depletion in cancer with the benefits of NAD+ restoration in chronic diseases.

Other names

NAD+ biosynthetic enzymesNAD+ metabolic enzymesNAD+ synthesis enzymesNicotinamide adenine dinucleotide synthesis enzymes

Inhibition of rate-limiting enzymes (e.g., NAMPT, IDO1) to deplete intracellular NAD+ levels and induce metabolic collapse in cancer cells, or supplementation of NAD+ precursors and activation of biosynthetic enzymes to restore NAD+ levels in aging and metabolic diseases.