Nicotinamide adenine dinucleotide synthesis pathway enzymes (NAD+ synthesis enzymes)

Nicotinamide adenine dinucleotide (NAD+) synthesis pathway enzymes are a group of proteins responsible for the production and maintenance of NAD+, a vital coenzyme for redox reactions and a substrate for signaling enzymes like sirtuins and PARPs (NIH, 2020; MDPI, 2021). The pathway includes de novo synthesis from tryptophan (via IDO1/TDO), the Preiss-Handler pathway from nicotinic acid (via NAPRT), and the salvage pathway from nicotinamide (via NAMPT) or nicotinamide riboside (via NRK) (NIH, 2018; ResearchGate, 2015). These enzymes are critical for cellular energy metabolism, DNA repair, and genomic stability (MDPI, 2021). In cancer, enzymes like NAMPT and IDO1 are often overexpressed to meet high metabolic demands, making them targets for inhibitory drugs like FK866 and epacadostat (NIH, 2019; MDPI, 2022). Conversely, in aging and neurodegenerative diseases, restoring NAD+ levels through precursors or enzyme activation is a major therapeutic strategy to improve mitochondrial function and cellular resilience (NIH, 2016; MDPI, 2021). Additionally, the compartmentalization of these enzymes in the nucleus, mitochondria, and cytoplasm allows for the independent regulation of distinct NAD+ pools (NIH, 2020). Therapeutic challenges include the potential for systemic toxicity, such as thrombocytopenia, and the need for precise patient selection based on enzyme expression profiles (NIH, 2018).

Other names

NAD+ biosynthetic enzymesNAD+ metabolic enzymesNicotinamide adenine dinucleotide biosynthetic pathway enzymesNAMPTIDO1NMNATNAPRTNRKTDO

Inhibition of rate-limiting enzymes such as NAMPT and IDO1 to deplete NAD+ levels in cancer cells, or activation/supplementation of precursors to restore NAD+ levels in aging and neurodegeneration (NIH, 2018; MDPI, 2021).