New functions of a long‐known molecule

Abstract

Over the past decades, the pyridine nucleotides have been established as important molecules in signaling pathways, besides their well known function in energy transduction. Similarly to another molecule carrying such dual functions, ATP, NAD(P) 1 may serve as substrate for covalent protein modification or as precursor of biologically active compounds.Protein modification is catalyzed by ADP-ribosyl transferases that attach the ADP-ribose moiety of NAD 1 to specific amino-acid residues of the acceptor proteins. For a number of ADP ribosylation reactions the specific transferases and their target proteins have been identified. As a result of the modification, the biological activity of the acceptor proteins may be severely changed. The cell nucleus contains enzymes catalyzing the transfer of ADP-ribose polymers (polyADP-ribose) onto the acceptor proteins. The best known enzyme of this type is poly(ADP-ribose) polymerase 1 (PARP1), which has been implicated in the regulation of several important processes including DNA repair, transcription, apoptosis, neoplastic transformation and others.The second group of reactions leads to the synthesis of an unusual cyclic nucleotide, cyclic ADP-ribose (cADPR). Moreover, the enzymes catalyzing this reaction may also replace the nicotinamide of NADP 1 by nicotinic acid resulting in the synthesis of nicotinic acid adenine dinucleotide phosphate (NAADP 1 ). Both cADPR and NAADP 1 have been reported to be potent intracellular calcium-mobilizing agents. In concert with inositol 1,4,5-trisphosphate, they participate in cytosolic calcium regulation by releasing calcium from intracellular stores.

Involvement of P2X receptors in the NAD+-induced rise in [Ca2+]i in human monocytes

“…3a), a potent activator at both the P2X 1 [26] and P2X 7 [23] receptor, they failed to respond to the subsequent application of NAD + . Presumably, BzATP occupies binding sites such as P2X 1 and/or P2X 7 receptors that are essential for NAD + to exert its effects. On the other hand, when NAD + was added to monocytes prior to BzATP, the BzATP-induced calcium response was only slightly reduced (Fig.…”

“…There is increasing evidence that nicotinamide adenine dinucleotide (NAD + ), in addition to its intracellular role, also functions as an extracellular signaling molecule [1]. NAD + can serve as a substrate for mono-ADP-ribosyltransferases (ARTs) that catalyze the transfer of the ADP-ribose moiety from NAD + to target proteins [2], or it can be used by CD38 and CD157, also called BST-1, for the synthesis of metabolically active degradation products involved in Ca 2+ signaling.…”

Thermococcus kodakarensis : the key to affordable biohydrogen production

“…In addition to its redox function, NAD + serves as a substrate for mono-and poly-ADP ribosylation, participates in histone deacetylation, and contributes to the production of the signaling molecule cyclic ADP-ribose. Most of these reactions have been characterized in eukaryotes, but the ribosylation reactions also play a role in toxin production by pathogenic bacteria [155,156].…”

“…The consumption of NADP + is thus connected to the consumption of NAD + and to the regulation of various major biological activities such as DNA repair, gene expression, apoptosis, nitrogen fixation, and calcium homeostasis [142,148,152,155,156]. [148,155,160,161].…”

High-Performance Liquid Chromatographic Technique for Detection of a Fluorescent Analogue of ADP-Ribose in Isolated Blood Vessel Preparations

“…Nicotinamide adenine dinucleotide (NAD ϩ ) can play a dual role as an energy and signal transducer and may also be used as a substrate for synthesis of biologically active compounds such as cyclic adenosine 5Ј-diphosphate ribose (cADPR) 2 and adenosine 5Ј-diphosphate ribose (ADPR) (1). ADPR is produced by hydrolysis of NAD ϩ by NAD ϩ glycohydrolase or hydrolysis of cADPR by cADPR hydrolase (2,3).…”