乳酸脱氢酶与氧化还原稳健性的相互调节
Mutual regulation of lactate dehydrogenase and redox robustness.
作者信息
Lin Yijun, Wang Yan, Li Pei-Feng
机构信息
Xiamen Cardiovascular Hospital, Xiamen University, Xiamen, China.
出版信息
Front Physiol. 2022 Nov 4;13:1038421. doi: 10.3389/fphys.2022.1038421. eCollection 2022.
The nature of redox is electron transfer; in this way, energy metabolism brings redox stress. Lactate production is associated with NAD regeneration, which is now recognized to play a role in maintaining redox homeostasis. The cellular lactate/pyruvate ratio could be described as a proxy for the cytosolic NADH/NAD ratio, meaning lactate metabolism is the key to redox regulation. Here, we review the role of lactate dehydrogenases in cellular redox regulation, which play the role of the direct regulator of lactate-pyruvate transforming. Lactate dehydrogenases (LDHs) are found in almost all animal tissues; while LDHA catalyzed pyruvate to lactate, LDHB catalyzed the reverse reaction . LDH enzyme activity affects cell oxidative stress with NAD/NADH regulation, especially LDHA recently is also thought as an ROS sensor. We focus on the mutual regulation of LDHA and redox robustness. ROS accumulation regulates the transcription of LDHA. Conversely, diverse post-translational modifications of LDHA, such as phosphorylation and ubiquitination, play important roles in enzyme activity on ROS elimination, emphasizing the potential role of the ROS sensor and regulator of LDHA.
氧化还原的本质是电子转移;通过这种方式,能量代谢带来氧化还原应激。乳酸生成与NAD再生相关,现在人们认识到NAD再生在维持氧化还原稳态中发挥作用。细胞内乳酸/丙酮酸比值可被视为胞质NADH/NAD比值的替代指标,这意味着乳酸代谢是氧化还原调节的关键。在此,我们综述了乳酸脱氢酶在细胞氧化还原调节中的作用,其在乳酸-丙酮酸转化中起直接调节作用。乳酸脱氢酶(LDHs)几乎存在于所有动物组织中;LDHA催化丙酮酸生成乳酸,而LDHB催化相反的反应。LDH酶活性通过NAD/NADH调节影响细胞氧化应激,尤其是LDHA最近也被认为是一种ROS传感器。我们重点关注LDHA与氧化还原稳健性的相互调节。ROS积累调节LDHA的转录。相反,LDHA的多种翻译后修饰,如磷酸化和泛素化,在酶清除ROS的活性中起重要作用,强调了LDHA作为ROS传感器和调节因子的潜在作用。