Overview of pyridine nucleotides review series

Abstract

Pyridine nucleotides are abundant soluble coenzymes and they undergo reversible oxidation and reduction in several biological electron-transfer reactions. They are comprised of two mononucleotides, adenosine monophosphate and nicotinamide mononucleotide, and are present as oxidized and reduced nicotinamide adenine dinucleotides in their unphosphorylated (NAD(+) and NADH) and phosphorylated (NADP(+) and NADPH) forms. In the past, pyridine nucleotides were considered to be primarily electron-shuttling agents involved in supporting the activity of enzymes that catalyze oxidation-reduction reactions. However, it has recently been demonstrated that pyridine nucleotides and the balance between the oxidized and reduced forms play a wide variety of pivotal roles in cellular functions as important interfaces, beyond their coenzymatic activity. These include maintenance of redox status, cell survival and death, ion channel regulation, and cell signaling under normal and pathological conditions. Furthermore, targeting pyridine nucleotides could potentially provide therapeutically useful avenues for treating cardiovascular diseases. This review series will highlight the functional significance of pyridine nucleotides and underscore their physiological role in cardiovascular function and their clinical relevance to cardiovascular medicine.

Figure. Schematic of pyridine nucleotides biosynthesis and their functions

Pyridine nucleotides are involved in a wide variety of cellular functions, including energy production, metabolism, redox reactions, survival/death, and ion channels under normal and pathological conditions. Trp, tryptophan; Na, nicotinic acid; QA, quinolinic acid; NaMN, nicotinic acid mononucleotide; Nam, nicotinamide; NMN, nicotinamide mononucleotide; NR, nicotinamide riboside; Nampt, nicotinamide phosphoribosyltransferase; Nmnat, Nam/Na mononucleotide adenylyl transferase; NADK, NAD kinase; NaPRT, Na phosphoribosyltransferase; QAPRT, quinolate phosphoribosyltransferase; NaMNAT, nicotinic acid mononucleotide adenylyltransferase; NaAD, nicotinic acid adenine dinucleotide; NaDS, NAD synthase; Trx, thioredoxin; Nox, NADPH oxidase; GSH, glutathione; Redox, reduction-oxidation; ROS, reactive oxygen species; PARP, poly(ADP-ribose) polymerases; MART, mono-ADP-ribose transferase; cADP, cyclic ADP-ribose synthase; ETC, electron transport chain.