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作 者:Luojun Chen Xiaoke Xing Pingfeng Zhang Lulu Chen Huadong Pei
机构地区:[1]Cancer Center,Renmin Hospital of Wuhan University,Wuhan,Hubei 430062,China [2]Department of Oncology,Georgetown Lombardi Comprehensive Cancer Center,Georgetown University Medical Center,Washington,DC 20057,USA
出 处:《Genes & Diseases》2024年第5期285-299,共15页基因与疾病(英文)
摘 要: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.
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