Glutamine Deficiency Promotes Immune and Endothelial Cell Dysfunction in COVID-19.
Glutamine Deficiency Promotes Immune and Endothelial Cell Dysfunction in COVID-19.
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DOI：
10.3390/ijms24087593
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发表时间：
2023-04-20
影响因子：
5.6
通讯作者：
Durante, William
中科院分区：
文献类型：
--
作者：
Durante, William
关键词：
冠状病毒病2019年(新冠肺炎)大流行已导致全球近700万人死亡。虽然疫苗接种和新的抗病毒药物已经大大减少了新冠肺炎的病例数量，但仍然需要更多的治疗策略来对抗这种致命的疾病。越来越多的临床数据发现，新冠肺炎患者循环中的谷氨酰胺缺乏与疾病严重程度有关。谷氨酰胺是一种半必需的氨基酸，它被代谢成过多的代谢物，作为免疫和内皮细胞功能的中枢调节剂。大部分谷氨酰胺被线粒体酶谷氨酰胺酶(GLS)代谢成谷氨酸和氨。值得注意的是，新冠肺炎中的谷氨酰胺合成酶活性上调，有利于谷氨酰胺的分解代谢。谷氨酰胺代谢的这种紊乱可能引起免疫和内皮细胞功能障碍，从而导致严重感染、炎症、氧化应激、血管痉挛和凝血障碍，从而导致血管闭塞、多器官衰竭和死亡。恢复谷氨酰胺、其代谢产物和/或其下游效应物的血浆浓度的策略，结合抗病毒药物，是一种很有前途的治疗方法，可能会恢复免疫和内皮细胞功能，并防止新冠肺炎患者发生闭塞性血管疾病。
The coronavirus disease 2019 (COVID-19) pandemic has caused the death of almost 7 million people worldwide. While vaccinations and new antiviral drugs have greatly reduced the number of COVID-19 cases, there remains a need for additional therapeutic strategies to combat this deadly disease. Accumulating clinical data have discovered a deficiency of circulating glutamine in patients with COVID-19 that associates with disease severity. Glutamine is a semi-essential amino acid that is metabolized to a plethora of metabolites that serve as central modulators of immune and endothelial cell function. A majority of glutamine is metabolized to glutamate and ammonia by the mitochondrial enzyme glutaminase (GLS). Notably, GLS activity is upregulated in COVID-19, favoring the catabolism of glutamine. This disturbance in glutamine metabolism may provoke immune and endothelial cell dysfunction that contributes to the development of severe infection, inflammation, oxidative stress, vasospasm, and coagulopathy, which leads to vascular occlusion, multi-organ failure, and death. Strategies that restore the plasma concentration of glutamine, its metabolites, and/or its downstream effectors, in conjunction with antiviral drugs, represent a promising therapeutic approach that may restore immune and endothelial cell function and prevent the development of occlusive vascular disease in patients stricken with COVID-19.
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DOI：
10.1007/s10096-020-04138-6
发表时间：
2021-05
期刊：
European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology
影响因子：
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发表时间：
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影响因子：
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