Division of Hematology and Oncology, Department of Medicine, SUNY Downstate Health Sciences University, Brooklyn, NY, USA.
Division of Internal Medicine, Department of Medicine, SUNY Downstate Health Sciences University, Brooklyn, NY, USA.
Ann Hematol. 2022 Aug;101(8):1645-1654. doi: 10.1007/s00277-022-04867-y. Epub 2022 May 14.
Oxidative stress is a major contributor to the pathophysiology of sickle cell disease (SCD) including hemolysis and vaso-occlusive crisis (VOC). L-glutamine is a conditionally essential amino acid with important roles, including the synthesis of antioxidants, such as reduced glutathione and the cofactors NAD(H) and NADP(H), as well as nitric oxide. Given the increased levels of oxidative stress and lower (NADH):(NAD + + NADH) ratio in sickle erythrocytes that adversely affects the blood rheology compared to normal red blood cells, L-glutamine was investigated for its therapeutic potential to reduce VOC. While L-glutamine was approved by the United States (US) Food and Drug Administration to treat SCD, its impact on the redox environment in sickle erythrocytes is not fully understood. The mechanism through which L-glutamine reduces VOC in SCD is also not clear. In this paper, we will summarize the results of the Phase 3 study that led to the approval of L-glutamine for treating SCD and discuss its assumed mechanisms of action. We will examine the role of L-glutamine in health and propose how the extra-erythrocytic functions of L-glutamine might contribute to its beneficial effects in SCD. Further research into the role of L-glutamine on extra-erythrocyte functions might help the development of an improved formulation with more efficacy.
氧化应激是导致镰状细胞病（SCD）病理生理学的主要因素，包括溶血和血管阻塞性危象（VOC）。L-谷氨酰胺是一种条件必需氨基酸，具有重要作用，包括合成抗氧化剂，如还原型谷胱甘肽以及辅酶 NAD（H）和 NADP（H），以及一氧化氮。由于镰状红细胞中氧化应激水平升高和（NADH）：（NAD + + NADH）比值降低，这会影响血液流变学，与正常红细胞相比不利，因此研究了 L-谷氨酰胺治疗 VOC 的潜在治疗作用。虽然 L-谷氨酰胺已被美国（US）食品和药物管理局批准用于治疗 SCD，但它对镰状红细胞氧化还原环境的影响尚未完全清楚。L-谷氨酰胺在 SCD 中降低 VOC 的机制也不清楚。在本文中，我们将总结导致 L-谷氨酰胺批准用于治疗 SCD 的 3 期研究结果，并讨论其假定的作用机制。我们将研究 L-谷氨酰胺在健康中的作用，并提出 L-谷氨酰胺的细胞外功能如何有助于其在 SCD 中的有益作用。进一步研究 L-谷氨酰胺对细胞外功能的作用可能有助于开发更有效的改良制剂。
