据介绍，代谢需求在发育过程中各不相同，人们对代谢活动如何影响细胞特化的理解尚不完整。
研究人员描述了红系细胞成熟所需的从谷氨酰胺分解代谢到合成的转变。谷氨酰胺合成酶（GS）是演化中最古老的功能基因之一，在红系成熟过程中被激活，对血红素生物合成产生的铵进行解毒，血红素生物合成上调以支持血红蛋白的产生。
小鼠红系前体中GS的缺失导致铵积累和氧化应激，损害红系成熟和贫血恢复。在β-地中海贫血中，GS活性受到蛋白质氧化的抑制，导致谷氨酸和铵的积累，而增强GS活性可以缓解代谢和病理缺陷。
总之，这一研究结果确定了一种演化上保守的代谢适应，可以用来治疗常见的红细胞疾病。
附：英文原文
Title: A glutamine metabolic switch supports erythropoiesis
Author: Junhua Lyu, Zhimin Gu, Yuannyu Zhang, Hieu S. Vu, Christophe Lechauve, Feng Cai, Hui Cao, Julia Keith, Valentina Brancaleoni, Francesca Granata, Irene Motta, Maria Domenica Cappellini, Lily Jun-Shen Huang, Ralph J. DeBerardinis, Mitchell J. Weiss, Min Ni, Jian Xu
Issue&Volume: 2024-11-15
Abstract: Metabolic requirements vary during development, and our understanding of how metabolic activity influences cell specialization is incomplete. Here, we describe a switch from glutamine catabolism to synthesis required for erythroid cell maturation. Glutamine synthetase (GS), one of the oldest functioning genes in evolution, is activated during erythroid maturation to detoxify ammonium generated from heme biosynthesis, which is up-regulated to support hemoglobin production. Loss of GS in mouse erythroid precursors caused ammonium accumulation and oxidative stress, impairing erythroid maturation and recovery from anemia. In β-thalassemia, GS activity is inhibited by protein oxidation, leading to glutamate and ammonium accumulation, whereas enhancing GS activity alleviates the metabolic and pathological defects. Our findings identify an evolutionarily conserved metabolic adaptation that could potentially be leveraged to treat common red blood cell disorders.
DOI: adh9215
Source: https://www.science.org/doi/10.1126/science.adh9215