Lie-Venema H, Hakvoort T B, van Hemert F J, Moorman A F, Lamers W H
Department of Anatomy and Embryology, University of Amsterdam, The Netherlands.
Prog Nucleic Acid Res Mol Biol. 1998;61:243-308. doi: 10.1016/s0079-6603(08)60829-6.
Glutamine synthetase, the enzyme that catalyzes the ATP-dependent conversion of glutamate and ammonia into glutamine, is expressed in a tissue-specific and developmentally controlled manner. The first part of this review focuses on its spatiotemporal pattern of expression, the factors that regulate its levels under (patho)physiological conditions, and its role in glutamine, glutamate, and ammonia metabolism in mammals. Glutamine synthetase protein stability is more than 10-fold reduced by its product glutamine and by covalent modifications. During late fetal development, translational efficiency increases more than 10-fold. Glutamine synthetase mRNA stability is negatively affected by cAMP, whereas glucocorticoids, growth hormone, insulin (all positive), and cAMP (negative) regulate its rate of transcription. The signal transduction pathways by which these factors may regulate the expression of glutamine synthetase are briefly discussed. The second part of the review focuses on the evolution, structure, and transcriptional regulation of the glutamine synthetase gene in rat and chicken. Two enhancers (at -6.5 and -2.5 kb) were identified in the upstream region and two enhancers (between +156 and +857 bp) in the first intron of the rat glutamine synthetase gene. In addition, sequence analysis suggests a regulatory role for regions in the 3' untranslated region of the gene. The immediate-upstream region of the chicken glutamine synthetase gene is responsible for its cell-specific expression, whereas the glucocorticoid-induced developmental appearance in the neural retina is governed by its far-upstream region.
谷氨酰胺合成酶可催化谷氨酸和氨在ATP依赖下转化为谷氨酰胺，其表达具有组织特异性且受发育调控。本综述的第一部分重点关注其表达的时空模式、在（病理）生理条件下调节其水平的因素，以及它在哺乳动物谷氨酰胺、谷氨酸和氨代谢中的作用。谷氨酰胺合成酶蛋白的稳定性因其产物谷氨酰胺和共价修饰而降低10倍以上。在胎儿发育后期，翻译效率提高10倍以上。谷氨酰胺合成酶mRNA的稳定性受到cAMP的负面影响，而糖皮质激素、生长激素、胰岛素（均为正向作用）和cAMP（负向作用）调节其转录速率。本文简要讨论了这些因素调节谷氨酰胺合成酶表达的信号转导途径。综述的第二部分重点关注大鼠和鸡谷氨酰胺合成酶基因的进化、结构和转录调控。在大鼠谷氨酰胺合成酶基因的上游区域鉴定出两个增强子（分别位于-6.5和-2.5 kb处），在第一个内含子中鉴定出两个增强子（位于+156至+857 bp之间）。此外，序列分析表明该基因3'非翻译区的区域具有调控作用。鸡谷氨酰胺合成酶基因的紧邻上游区域负责其细胞特异性表达，而神经视网膜中糖皮质激素诱导的发育出现则受其远上游区域的控制。
