NAD+ Precursors and the Salvage Pathway

NAD+ Precursors and the Salvage Pathway

There are several pathways by which NAD+ can be generated. Still, one stands out called the salvage pathway because it is the most abundant in mammalian cells (the others are called the Preiss-Handler pathway, in which NAD+ is synthesized from nicotinic acid, and the de novo synthesis pathways, which starts from tryptophan).

The salvage pathway works based on the concept that NAD+ is constantly turning over; in essence, it is an NAD+ recycling pathway. When NAD+ gets consumed by enzymes, often participating in physiologic processes including DNA repair, metabolism, and cell death, it gets converted into nicotinamide (NAM) as a byproduct.

There are only two steps in the salvage pathway. The conversion of NAM primarily determines the rate of NAD+ synthesis in this pathway to nicotinamide mononucleotide (NMN) in this first step. Then, NMN is converted to NAD+ in the second step. All in all, to sustain NAD+ levels, NAM can be recycled back to NAD+ via the salvage pathway by being converted to NMN.

In addition to NAM, NMN can be generated by another NAD+ precursor called nicotinamide riboside (NR). Instead of being recycled from NAM emanating from NAD+ consumption, NR gets converted into NMN inside the cell by an enzyme family called nicotinamide riboside kinases (NRKs).

CH TRADITIONAL
CH TRADITIONAL