Pharmacology and Potential Implications of Nicotinamide Adenine Dinucleotide Precursors.
Pharmacology and Potential Implications of Nicotinamide Adenine Dinucleotide Precursors.
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烟酰胺腺嘌呤二核苷酸前体的药理学和潜在影响
DOI：
10.14336/ad.2021.0523
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发表时间：
2021-12
影响因子：
7.4
通讯作者：
Qin ZH
中科院分区：
文献类型：
--
作者：
She J;Sheng R;Qin ZH
辅酶I（烟酰胺腺嘌呤二核苷酸，NAD+/NADH）和辅酶II（烟酰胺腺嘌呤二核苷酸磷酸，NADP+/NADPH）参与哺乳动物细胞中的各种生物学过程。NAD+通过从头和补救途径合成，而辅酶II不能从头合成。NAD+是辅酶II的前体。虽然NAD+在正常条件下合成量充足，但随着年龄的增长和某些疾病条件下，观察到由于过度消耗和合成减少而导致的供应短缺。一些研究已经证明，在广泛的组织中，如肝脏，皮肤，肌肉，胰腺和脂肪，NAD+的水平随着年龄的增长而下降。然而，在脑组织中，老年人的NADH水平逐渐升高，NAD+水平逐渐降低。NAD+/NADH的比率指示细胞的氧化还原状态。该比率的降低影响细胞无氧糖酵解和氧化磷酸化功能，从而降低细胞产生ATP的能力。因此，在某些疾病条件下或在老年人中增加外源性NAD+供应可能是有益的。NAD+的前体已被广泛探索，并据报道可有效增加NAD+水平，并具有广泛的功能。在这篇综述文章中，我们讨论了NAD+前体的药代动力学和药效学。
Coenzyme I (nicotinamide adenine dinucleotide, NAD+/NADH) and coenzyme II (nicotinamide adenine dinucleotide phosphate, NADP+/NADPH) are involved in various biological processes in mammalian cells. NAD+ is synthesised through the de novo and salvage pathways, whereas coenzyme II cannot be synthesised de novo. NAD+ is a precursor of coenzyme II. Although NAD+ is synthesised in sufficient amounts under normal conditions, shortage in its supply due to over consumption and its decreased synthesis has been observed with increasing age and under certain disease conditions. Several studies have proved that in a wide range of tissues, such as liver, skin, muscle, pancreas, and fat, the level of NAD+ decreases with age. However, in the brain tissue, the level of NADH gradually increases and that of NAD+ decreases in aged people. The ratio of NAD+/NADH indicates the cellular redox state. A decrease in this ratio affects the cellular anaerobic glycolysis and oxidative phosphorylation functions, which reduces the ability of cells to produce ATP. Therefore, increasing the exogenous NAD+ supply under certain disease conditions or in elderly people may be beneficial. Precursors of NAD+ have been extensively explored and have been reported to effectively increase NAD+ levels and possess a broad range of functions. In this review article, we discuss the pharmacokinetics and pharmacodynamics of NAD+ precursors.