细胞中 NAD(H) 和 NADP(H) 的稳态调节。
Homeostatic regulation of NAD(H) and NADP(H) in cells.
发表日期:2024 Sep
作者:
Luojun Chen, Xiaoke Xing, Pingfeng Zhang, Lulu Chen, Huadong Pei
来源:
ANTIOXIDANTS & REDOX SIGNALING
摘要:
烟酰胺腺嘌呤二核苷酸(NAD)/还原型NAD(NADH)和烟酰胺腺嘌呤二核苷酸磷酸(NADP)/还原型NADP(NADPH)是参与多种代谢途径和细胞过程的必需代谢物。 NAD 和 NADH 氧化还原对在分解代谢氧化还原反应中起着至关重要的作用,而 NADPH 对于细胞合成代谢和抗氧化反应至关重要。维持 NAD(H) 和 NADP(H) 稳态对于正常生理活动至关重要,并通过 NAD(H) 和 NADP(H) 之间的生物合成、消耗、回收和转化等多种机制进行严格调节。 NAD(H) 和 NADP(H) 之间的转化由 NAD 激酶 (NADK) 和 NADP(H) 磷酸酶 [特别是后生动物 SpoT 同源物-1 (MESH1) 和夜曲素 (NOCT)] 控制。 NADK 促进 NAD 合成 NADP,而 MESH1 和 NOCT 将 NADP(H) 转化为 NAD(H)。在这篇综述中,我们总结了 NAD(H) 和 NADP(H) 的生理作用,并从三个关键方面讨论了 NAD(H) 和 NADP(H) 稳态的调节机制:NADK 的转录和翻译后调节、NADK 的作用、 MESH1和NOCT在维持NAD(H)和NADP(H)稳态中的作用,以及生物钟对NAD(H)和NADP(H)稳态的影响。总之,NADK、MESH1 和 NOCT 是各种细胞过程不可或缺的组成部分,调节 NAD(H) 和 NADP(H) 稳态。这些酶的失调会导致各种人类疾病,例如癌症和代谢紊乱。因此,旨在恢复 NAD(H) 和 NADP(H) 稳态的策略有望成为这些疾病的新治疗方法。© 2024 作者。 Elsevier B.V. 代表科爱通讯有限公司提供的出版服务
Nicotinamide adenine dinucleotide (NAD+)/reduced NAD+ (NADH) and nicotinamide adenine dinucleotide phosphate (NADP+)/reduced NADP+ (NADPH) are essential metabolites involved in multiple metabolic pathways and cellular processes. NAD+ and NADH redox couple plays a vital role in catabolic redox reactions, while NADPH is crucial for cellular anabolism and antioxidant responses. Maintaining NAD(H) and NADP(H) homeostasis is crucial for normal physiological activity and is tightly regulated through various mechanisms, such as biosynthesis, consumption, recycling, and conversion between NAD(H) and NADP(H). The conversions between NAD(H) and NADP(H) are controlled by NAD kinases (NADKs) and NADP(H) phosphatases [specifically, metazoan SpoT homolog-1 (MESH1) and nocturnin (NOCT)]. NADKs facilitate the synthesis of NADP+ from NAD+, while MESH1 and NOCT convert NADP(H) into NAD(H). In this review, we summarize the physiological roles of NAD(H) and NADP(H) and discuss the regulatory mechanisms governing NAD(H) and NADP(H) homeostasis in three key aspects: the transcriptional and posttranslational regulation of NADKs, the role of MESH1 and NOCT in maintaining NAD(H) and NADP(H) homeostasis, and the influence of the circadian clock on NAD(H) and NADP(H) homeostasis. In conclusion, NADKs, MESH1, and NOCT are integral to various cellular processes, regulating NAD(H) and NADP(H) homeostasis. Dysregulation of these enzymes results in various human diseases, such as cancers and metabolic disorders. Hence, strategies aiming to restore NAD(H) and NADP(H) homeostasis hold promise as novel therapeutic approaches for these diseases.© 2024 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.