The NAD effector pathway is a regulatory system that controls the biosynthesis and salvage of nicotinamide adenine dinucleotide (NAD⁺), a central coenzyme in redox metabolism, energy production, and cellular signaling. This pathway is regulated by NadR, a dual-function protein that acts as both a transcriptional repressor and, in some organisms, a nicotinamide riboside kinase. NadR is a 45-kDa bifunctional regulator protein. In vivo genetic studies indicate that NadR represses three genes involved in the biosynthesis of NAD. It also participates with an integral membrane protein (PnuC) in the import of nicotinamide mononucleotide, an NAD precursor. NadR senses intracellular NAD⁺ levels and represses the transcription of genes involved in NAD⁺ biosynthesis and uptake when NAD⁺ is abundant. When NAD⁺ levels are low, NadR-mediated repression is relieved, allowing the expression of genes that support NAD⁺ production and import. Key genes in the NadR regulog include: nadA – Encodes quinolinate synthase, a key enzyme in the de novo NAD⁺ biosynthesis pathway. It catalyzes the formation of quinolinic acid from iminoaspartate and dihydroxyacetone phosphate, an essential early step in NAD⁺ biosynthesis. pnuC – Encodes a nicotinamide riboside transporter, which facilitates the uptake of extracellular nicotinamide riboside, enabling NAD⁺ salvage through conversion of imported precursors.

NAD References