Top, a schematic representation of de novo NAD+ biosynthesis in bacteria starting from aspartate. Nicotinate recycling intersects the de novo pathway at NAMN. Bottom, a schematic representation of recycling of nicotinamide and NMN as observed for microbes. The reaction to generate NMN is catalyzed by bacterial NAD+-dependent DNA ligases. The salvage of nicotinamide is achieved by obligate nicotinamidase-catalyzed hydrolysis to form nicotinate. Nicotinamidase in yeast (PNC1) is subject to stress-regulated transcription. Nicotinamidase levels appear to regulate nicotinamide levels in the yeast, causing increased sirtuin activity, as explained in the text.
Top, a schematic representation of de novo NAD+ biosynthesis in organisms that use tryptophan as a source for NAD+. Like the aspartate-based pathway, formation of quinolinate is the crucial step that leads to the nicotinate ring system via formation of NAMN. Nicotinate recycling is shown to intersect the NAD+-biosynthetic pathway at NAMN. Bottom, a schematic representation of paths of metabolism for human nicotinamide, nicotinic acid, and nicotinamide riboside that lead to formation of NAD+. Nicotinamide is converted directly within cells by nampt. This enzyme was first named PBEF. Evidence suggests that this enzyme is regulated by cell stress and can dramatically alter intracellular NAD+ concentrations. Humans do not appear to have a nicotinamidase enzyme, which means that nicotinic acid and nicotinamide are incorporated into NAD+ via nonoverlapping pathways. As explained in the text, the enzyme nicotinamide/nicotinate mononucleotide adenylyltransferase (nmnat-1, nmnat-2, and nmnat-3) serves in both pathways by virtue of its ability to accept either NMN or NAMN as a substrate.