Enzymology of NAD+ synthesis.
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.
Magni
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G
Istituto di Biochimica, Facoltà di Medicina, Università di Ancona, Italy.
Amici
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A
Emanuelli
M
M
Raffaelli
N
N
Ruggieri
S
S
D019732:Amide Synthases / Q000378:metabolism; D000581:Amidohydrolases / Q000378:metabolism; D000818:Animals; D006801:Humans; D009243:NAD / Q000096:biosynthesis*; D009525:Niacin / Q000378:metabolism; D009535:Nicotinamidase / Q000378:metabolism; D009612:Nicotinamide-Nucleotide Adenylyltransferase / Q000378:metabolism; D010430:Pentosyltransferases / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D011755:Pyrophosphatases / Q000378:metabolism; D017378:Quinolinic Acid / Q000378:metabolism; D000098553:Nicotinate-Nucleotide Diphosphorylase (Carboxylating)
D009243:NAD; D009525:Niacin; D010430:Pentosyltransferases; D000098553:Nicotinate-Nucleotide Diphosphorylase (Carboxylating); D017853:Phosphotransferases (Alcohol Group Acceptor); C021844:NAD kinase; D009612:Nicotinamide-Nucleotide Adenylyltransferase; D000581:Amidohydrolases; D009535:Nicotinamidase; C021861:nicotinamidenucleotide amidase; D011755:Pyrophosphatases; D019732:Amide Synthases; C038479:NAD+ synthase; D017378:Quinolinic Acid