Department of Biophysics, Panjab University, Chandigarh, 160014, India.
Inflammation. 2022 Dec;45(6):2091-2123. doi: 10.1007/s10753-022-01680-7. Epub 2022 May 19.
Lactate dehydrogenase (LDH) is a terminating enzyme in the metabolic pathway of anaerobic glycolysis with end product of lactate from glucose. The lactate formation is crucial in the metabolism of glucose when oxygen is in inadequate supply. Lactate can also be formed and utilised by different cell types under fully aerobic conditions. Blood LDH is the marker enzyme, which predicts mortality in many conditions such as ARDS, serious COVID-19 and cancer patients. Lactate plays a critical role in normal physiology of humans including an energy source, a signaling molecule and a pH regulator. Depending on the pH, lactate exists as the protonated acidic form (lactic acid) at low pH or as sodium salt (sodium lactate) at basic pH. Lactate can affect the immune system and act as a signaling molecule, which can provide a "danger" signal for life. Several reports provide evidence that the serum lactate represents a chemical marker of severity of disease similar to LDH under inflammatory conditions. Since the mortality rate is much higher among COVID-19 patients, associated with high serum LDH, this article is aimed to review the LDH as a therapeutic target and lactate as potential marker for monitoring treatment response of inflammatory diseases. Finally, the review summarises various LDH inhibitors, which offer potential applications as therapeutic agents for inflammatory diseases, associated with high blood LDH. Both blood LDH and blood lactate are suggested as risk factors for the mortality of patients in serious inflammatory diseases.
乳酸脱氢酶（LDH）是无氧糖酵解代谢途径中的终末酶，其终产物为葡萄糖衍生的乳酸。当氧气供应不足时，乳酸的形成对于葡萄糖的代谢至关重要。在完全有氧条件下，不同类型的细胞也可以形成和利用乳酸。血液 LDH 是一种标志物酶，可预测 ARDS、严重 COVID-19 和癌症患者等多种情况下的死亡率。乳酸在人类的正常生理中起着关键作用，包括能量来源、信号分子和 pH 调节剂。根据 pH 值的不同，乳酸以质子化的酸性形式（乳酸）存在于低 pH 值下，或以碱性 pH 值下的钠盐（乳酸钠）形式存在。乳酸可以影响免疫系统并作为信号分子发挥作用，为生命提供“危险”信号。有几项报告提供的证据表明，在炎症条件下，血清乳酸类似于 LDH，是疾病严重程度的化学标志物。由于 COVID-19 患者的死亡率高，与高血清 LDH 相关，本文旨在综述 LDH 作为治疗靶点和乳酸作为炎症性疾病治疗反应监测的潜在标志物。最后，综述总结了各种 LDH 抑制剂，这些抑制剂为高血液 LDH 相关的炎症性疾病提供了潜在的治疗应用。血液 LDH 和血液乳酸均被认为是严重炎症性疾病患者死亡的危险因素。
