The regulation of nicotinamide adenine dinucleotide biosynthesis by Nampt/PBEF/visfatin in mammals.
OBJECTIVE
Nicotinamide adenine dinucleotide (NAD) is a classic coenzyme in cellular redox reactions. Recently, NAD biochemistry has also been implicated in a broader range of biological functions in mammals, but the regulation of NAD biosynthesis has been poorly investigated. Recent progress in the field of NAD biochemistry has fueled new interest in the NAD biosynthetic pathways from its precursors and their physiological roles in metabolism. This review summarizes the latest knowledge on the NAD biosynthetic pathways and focuses on one of the key NAD biosynthetic enzymes, namely, nicotinamide phosphoribosyltransferase.


RESULTS
Mammals predominantly use nicotinamide rather than nicotinic acid as a precursor for NAD biosynthesis. Nicotinamide phosphoribosyltransferase (Nampt) is the rate-limiting enzyme that converts nicotinamide to nicotinamide mononucleotide in the NAD biosynthetic pathway from nicotinamide in mammals. The same protein has also been identified as a cytokine (pre-B-cell colony-enhancing factor or PBEF) or an insulin-mimetic hormone (visfatin).


CONCLUSIONS
We propose that the presumed multiple effects of Nampt/PBEF/visfatin may be entirely explained by its role as an intra and extracellular NAD biosynthetic enzyme. We also propose a new model of Namp/PBEF/visfatin-mediated systemic NAD biosynthesis and its possible physiological significance. Our model provides an important insight into developing preventive/therapeutic interventions for metabolic complications, such as obesity and diabetes.
Revollo
Javier R
JR
Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St Louis, Missouri 63110, USA.
Grimm
Andrew A
AA
Imai
Shin-ichiro
S
D000818:Animals; D016207:Cytokines / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D009243:NAD / Q000096:biosynthesis*; D054409:Nicotinamide Phosphoribosyltransferase; D011487:Protein Conformation
D016207:Cytokines; D009243:NAD; D054409:Nicotinamide Phosphoribosyltransferase; C495867:nicotinamide phosphoribosyltransferase, mouse