Enzymology of NAD+ synthesis

Abstract

Beyond its role as an essential coenzyme in numerous oxidoreductase reactions as well as respiration, there is growing recognition that NAD+ fulfills many other vital regulatory functions both as a substrate and as an allosteric effector. This review describes the enzymes involved in pyridine nucleotide metabolism, starting with a detailed consideration of the anaerobic and aerobic pathways leading to quinolinate, a key precursor of NAD+. Conversion of quinolinate and 5'-phosphoribosyl-1'-pyrophosphate to NAD+ and diphosphate by phosphoribosyltransferase is then explored before proceeding to a discussion the molecular and kinetic properties of NMN adenylytransferase. The salient features of NAD+ synthetase as well as NAD+ kinase are likewise presented. The remainder of the review encompasses the metabolic steps devoted to (a) the salvaging of various niacin derivatives, including the roles played by NAD+ and NADH pyrophosphatases, nicotinamide deamidase, and NMN deamidase, and (b) utilization of niacins by nicotinate phosphoribosyltransferase and nicotinamide phosphoribosyltransferase.