Nicotinamide adenine dinucleotide (NAD+) biosynthesis pathway (NAD+ biosynthesis pathway)

The Nicotinamide adenine dinucleotide (NAD+) biosynthesis pathway is a fundamental metabolic network that maintains cellular levels of NAD+, a vital coenzyme for redox reactions and a key substrate for enzymes like sirtuins, PARPs, and CD38 (Imai & Guarente, 2014). NAD+ is synthesized through three primary routes: the de novo pathway from tryptophan, the Preiss-Handler pathway from nicotinic acid, and the salvage pathway from nicotinamide or nicotinamide riboside (Yoshino et al., 2018). This system-level network is a major therapeutic target because NAD+ levels decline with age, contributing to metabolic dysfunction and neurodegeneration (Camacho-Pereira et al., 2016). Conversely, in oncology, the pathway is targeted for inhibition; cancer cells often overexpress NAMPT, the rate-limiting enzyme of the salvage pathway, to meet high energy demands (Galli et al., 2013). Drugs targeting this network include NAD+ precursors like nicotinamide riboside to boost levels and NAMPT inhibitors like daporinad to deplete them in tumors. Understanding the network's system-level dynamics is essential for balancing the benefits of NAD+ restoration against the risks of promoting tumor proliferation.

Other names

NAD+ metabolismNAD+ metabolic networkNicotinamide adenine dinucleotide synthesisPreiss-Handler pathwayNAD+ salvage pathway

Therapeutic strategies involve either increasing NAD+ availability through precursor supplementation (e.g., NR, NMN) to counteract age-related decline, or inhibiting rate-limiting enzymes like NAMPT to deplete NAD+ and induce apoptosis in cancer cells.