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.

中文翻译：

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烟酰胺腺嘌呤二核苷酸：心脏疾病的生物合成，消耗和治疗作用

烟酰胺腺嘌呤二核苷酸（NAD）是一种丰富的辅因子，在多种细胞过程中起着至关重要的作用。NAD可以从色氨酸开始从头合成，也可以从补救途径（从烟酸（NA），烟酰胺（NAM）或烟酰胺核糖苷（NR），称为烟酸/ B ₃维生素）的NAD前体开始，通过饮食供应或来自细胞NAD分解代谢。鉴于其氧化后的相互转化（NAD ⁺）和还原形式（NADH），NAD参与广泛的反应：调节细胞的氧化还原状态，能量代谢和线粒体生物发生。此外，NAD可以作为信号分子，是多种酶（例如sirtuins，聚-ADP-核糖聚合酶（PARP））和某些外切酶（例如CD38）的共底物，调节关键的生物学过程，例如基因表达，DNA修复，钙信号传导和昼夜节律节奏。考虑到心脏组织中存在大量线粒体，心脏具有最高的NAD水平，并且是最需要代谢的器官之一。在几种心力衰竭模型中，心肌NAD水平降低，这种降低是由线粒体功能障碍，代谢重塑和炎症引起的。新兴证据表明，通过补充NAD前体来调节NAD稳态具有改善心肌生物能和功能的治疗功效。这篇综述概述了对不同NAD生物合成途径的最新了解，以及其作为信号分子的作用，尤其是在心脏组织中。我们强调了在各种心脏病模型中保持NAD平衡的重要性，并阐明了旨在使用NAD促进剂作为治疗剂的潜在药理干预措施。