CÚRAM, SFI Research Centre for Medical Devices, University of Galway, Ireland.
CÚRAM, SFI Research Centre for Medical Devices, University of Galway, Ireland; School of Medicine, University of Galway, Ireland; Regenerative Medicine Institute (REMEDI), University of Galway, Ireland.
Biotechnol Adv. 2023 Oct;67:108184. doi: 10.1016/j.biotechadv.2023.108184. Epub 2023 Jun 7.
Glycosylation is how proteins and lipids are modified with complex carbohydrates known as glycans. The post-translational modification of proteins with glycans is not a template-driven process in the same way as genetic transcription or protein translation. Glycosylation is instead dynamically regulated by metabolic flux. This metabolic flux is determined by the concentrations and activities of the glycotransferase enzymes, which synthesise glycans, the metabolites that act as their precursors and transporter proteins. This review provides an overview of the metabolic pathways underlying glycan synthesis. Pathological dysregulation of glycosylation, particularly increased glycosylation occurring during inflammation, is also elucidated. The resulting inflammatory hyperglycosylation acts as a glycosignature of disease, and we report on the changes in the metabolic pathways which feed into glycan synthesis, revealing alterations to key enzymes. Finally, we examine studies in developing metabolic inhibitors targeting these critical enzymes. These results provide the tools for researchers investigating the role of glycan metabolism in inflammation and have helped to identify promising glycotherapeutic approaches to inflammation.
糖基化是蛋白质和脂质与复杂碳水化合物（称为聚糖）结合的方式。与遗传转录或蛋白质翻译一样，蛋白质与聚糖的翻译后修饰不是一个模板驱动的过程。糖基化是通过代谢通量动态调节的。这种代谢通量由糖基转移酶的浓度和活性决定，糖基转移酶合成聚糖，而代谢物作为其前体和转运蛋白。本综述提供了聚糖合成的代谢途径概述。还阐明了糖基化的病理性失调，特别是在炎症期间发生的过度糖基化。由此产生的炎症性高糖基化是疾病的糖基化特征，我们报告了参与聚糖合成的代谢途径的变化，揭示了关键酶的改变。最后，我们研究了针对这些关键酶的代谢抑制剂的开发。这些结果为研究糖代谢在炎症中的作用的研究人员提供了工具，并有助于确定有希望的抗炎糖治疗方法。
