Nicotinamide adenine dinucleotide: Biosynthesis, consumption and therapeutic role in cardiac diseases.

Cynthia Tannous, George W Booz, Raffaele Altara, Dina H Muhieddine, Mathias Mericskay, Marwan M Refaat, Fouad A Zouein

Acta physiologica (Oxford, England) 2021 Mar

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Nicotinamide adenine dinucleotide (NAD) is an abundant cofactor that plays crucial roles in several cellular processes. NAD can be synthesized de novo starting with tryptophan, or from salvage pathways starting with NAD precursors like nicotinic acid (NA), nicotinamide (NAM) or nicotinamide riboside (NR), referred to as niacin/B3 vitamins, arising from dietary supply or from cellular NAD catabolism. Given the interconversion between its oxidized (NAD+ ) and reduced form (NADH), NAD participates in a wide range of reactions: regulation of cellular redox status, energy metabolism and mitochondrial biogenesis. Plus, NAD acts as a signalling molecule, being a cosubstrate for several enzymes such as sirtuins, poly-ADP-ribose-polymerases (PARPs) and some ectoenzymes like CD38, regulating critical biological processes like gene expression, DNA repair, calcium signalling and circadian rhythms. Given the large number of mitochondria present in cardiac tissue, the heart has the highest NAD levels and is one of the most metabolically demanding organs. In several models of heart failure, myocardial NAD levels are depressed and this depression is caused by mitochondrial dysfunction, metabolic remodelling and inflammation. Emerging evidence suggests that regulating NAD homeostasis by NAD precursor supplementation has therapeutic efficiency in improving myocardial bioenergetics and function. This review provides an overview of the latest understanding of the different NAD biosynthesis pathways, as well as its role as a signalling molecule particularly in cardiac tissue. We highlight the significance of preserving NAD equilibrium in various models of heart diseases and shed light on the potential pharmacological interventions aiming to use NAD boosters as therapeutic agents. © 2020 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Citation

Cynthia Tannous, George W Booz, Raffaele Altara, Dina H Muhieddine, Mathias Mericskay, Marwan M Refaat, Fouad A Zouein. Nicotinamide adenine dinucleotide: Biosynthesis, consumption and therapeutic role in cardiac diseases. Acta physiologica (Oxford, England). 2021 Mar;231(3):e13551