Interplay between compartmentalized NAD+ synthesis and consumption: a focus on the PARP family.
Genes & development
confidence
Key findings
Review of NAD+ metabolism, compartmentalized synthesis and consumption, and regulation of PARPs and redox metabolism; no clinical/biological endpoints reported.
View source on PubMed (PMID 32029457) ↗
- Sample size
- N/A
- Population
- Not applicable (review article on NAD+ metabolism)
- Dosing
- N/A
- Duration
- N/A
- Route
- N/A
- Blinding
- not_reported
- Controls
- not_reported
- Drug class
- coenzyme
Full abstract
Nicotinamide adenine dinucleotide (NAD+) is an essential cofactor for redox enzymes, but also moonlights as a substrate for signaling enzymes. When used as a substrate by signaling enzymes, it is consumed, necessitating the recycling of NAD+ consumption products (i.e., nicotinamide) via a salvage pathway in order to maintain NAD+ homeostasis. A major family of NAD+ consumers in mammalian cells are poly-ADP-ribose-polymerases (PARPs). PARPs comprise a family of 17 enzymes in humans, 16 of which catalyze the transfer of ADP-ribose from NAD+ to macromolecular targets (namely, proteins, but also DNA and RNA). Because PARPs and the NAD+ biosynthetic enzymes are subcellularly localized, an emerging concept is that the activity of PARPs and other NAD+ consumers are regulated in a compartmentalized manner. In this review, I discuss NAD+ metabolism, how different subcellular pools of NAD+ are established and regulated, and how free NAD+ levels can control signaling by PARPs and redox metabolism.