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NAD激酶(NADKs)家族蛋白:代谢调控机制与疾病关联研究进展

程思雨¹, 潘宏宇², 王迪², 金煦², 程启梅², 高程杰², 石莉红^2,3,*

¹天津医科大学，细胞生态海河实验室，天津 300070；²中国医学科学院血液病医院(中国医学科学院血液学研究所)，血液与健康全国重点实验室，国家血液系统疾病临床医学研究中心，细胞生态海河实验室，天津 300020；³天津医学健康研究院，天津 301600

摘要

烟酰胺腺嘌呤二核苷酸[nicotinamide adenine dinucleotide，NAD(H)，包含氧化形式NAD+与还原形式NADH]和烟酰胺腺嘌呤二核苷酸磷酸[nicotinamide adenine dinucleotide phosphate，NADP(H)，包含氧化形式NADP+与还原形式NADPH]是代谢调控的核心分子对，在调控细胞能量代谢、氧化还原平衡及生物合成过程中发挥核心作用。细胞内NAD(H)与NADP(H)的比例失衡会导致严重的病理生理后果，引发多种疾病。NAD激酶(NAD kinases, NADKs)家族蛋白作为细胞内唯一负责磷酸化NAD(H)为NADP(H)的酶，在调控NAD(H)与NADP(H)平衡方面发挥着至关重要的作用。由于NADP+不具备跨亚细胞膜通透性，真核生物NADKs分为胞质NADK1 和线粒体NADK2 两种亚型。NADKs的催化活性可在转录水平及翻译后修饰层面受到调控，且NADKs表达或功能异常与多种疾病的发生、发展密切相关。NADKs靶向干预策略有望为肿瘤、代谢紊乱，以及其他相关疾病的临床治疗开辟新方向和新路径。

关键词： NADK1; NADK2; NAD(H); NADP(H)

NAD kinases (NADKs) family proteins: Advances in metabolic regulation mechanisms and disease associations

CHENG Si-Yu¹, PAN Hong-Yu², WANG Di², JIN Xu², CHENG Qi-Mei², GAO Cheng-Jie², SHI Li-Hong^2,3,*

¹Tianjin Medical University, Haihe Laboratory of Cell Ecosystem, Tianjin 300070, China；²State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China；³Tianjin Institutes of Health Science, Tianjin 301600, China

Abstract

Nicotinamide adenine dinucleotide [NAD(H), consisting of its oxidized form NAD+ and reduced form NADH] and nicotinamide adenine dinucleotide phosphate [NADP(H), consisting of its oxidized form NADP⁺ and reduced form NADPH] are core molecular pair governing metabolic regulation, which exert central functions in modulating cellular energy metabolism, redox homeostasis and biosynthesis. The imbalance of intracellular ratio of NAD(H) to NADP(H) can lead to serious pathophysiological consequences and trigger a wide spectrum of diseases. NAD kinases (NADKs), the sole enzymes that phosphorylate NAD(H) to NADP(H), therefore sit at the hub of NAD(H)/NADP(H) balance control. Because NADP+ cannot cross subcellular membranes, eukaryotic NADKs are classified into two isoforms: cytosolic NADK1 and mitochondrial NADK2. The catalytic activity of NADKs is regulated at the transcriptional and post-translational modification levels, and aberrant expression or dysfunction of NADKs is closely linked to the initiation and progression of numerous diseases. Targeted intervention strategies against NADKs thus represent a promising therapeutic avenue for the clinical treatments of tumors, metabolic disorders, and other related diseases.

Key words: NADK1; NADK2; NAD(H); NADP(H)

收稿日期：　　录用日期：

通讯作者：石莉红　　E-mail:

DOI: 10.13294/j.aps.2026.0072

引用本文：

程思雨, 潘宏宇, 王迪, 金煦, 程启梅, 高程杰, 石莉红. NAD激酶(NADKs)家族蛋白:代谢调控机制与疾病关联研究进展[J]. 生理学报 2026; 78 (4): 867-876.

CHENG Si-Yu, PAN Hong-Yu, WANG Di, JIN Xu, CHENG Qi-Mei, GAO Cheng-Jie, SHI Li-Hong. NAD kinases (NADKs) family proteins: Advances in metabolic regulation mechanisms and disease associations. Acta Physiol Sin 2026; 78 (4): 867-876 (in Chinese with English abstract).