Rodríguez-Bolaños Mónica, Perez-Montfort Ruy
Departamento de Bioquímica y Biología Estructural, Instituto de Fisiología Celular, Universidad Nacional Autónoma de Mexico, Circuito Exterior S/N, Cuidad Universitaria, Mexico City 04510, CDMX, Mexico.
Int J Mol Sci. 2025 Sep 10;26(18):8809. doi: 10.3390/ijms26188809.
This work reviews the complex role of the enzyme triosephosphate isomerase (TIM) (EC 5.3.1.1) within the context of diabetes, a prevalent metabolic disorder. It summarizes the main biochemical pathways, cellular mechanisms, and molecular interactions that highlight both the function of TIM and its implications in diabetes pathophysiology, particularly focusing on its regulatory role in glucose metabolism and insulin secretion. TIM's involvement is detailed from its enzymatic action in glycolysis, influencing the equilibrium between dihydroxyacetone phosphate and glyceraldehyde-3-phosphate, to its broader implications in cellular metabolic processes. The article highlights how mutations in TIM can lead to metabolic inefficiencies that exacerbate diabetic conditions. It discusses the interaction of TIM with various cellular pathways, including its role in the ATP-sensitive potassium channels in pancreatic beta cells, which are crucial for insulin release. Moreover, we indicate the impact of oxidative stress in diabetes, noting how TIM is affected by reactive oxygen species, which can disrupt normal cellular functions and insulin signaling. The enzyme's function is also tied to broader cellular and systemic processes, such as membrane fluidity and cellular signaling pathways, including the mammalian target of rapamycin, which are critical in the pathogenesis of diabetes and its complications. This review emphasizes the dual role of TIM in normal physiological and pathological states, suggesting that targeting TIM-related pathways could offer novel therapeutic strategies for managing diabetes. It encourages an integrated approach to understanding and treating diabetes, considering the multifaceted roles of biochemical players such as TIM that bridge metabolic, oxidative, and regulatory functions within the body.
这项工作在糖尿病（一种普遍的代谢紊乱疾病）的背景下，综述了磷酸丙糖异构酶（TIM）（EC 5.3.1.1）这一酶的复杂作用。它总结了主要的生化途径、细胞机制和分子相互作用，这些突出了TIM的功能及其在糖尿病病理生理学中的意义，尤其着重于其在葡萄糖代谢和胰岛素分泌中的调节作用。TIM的参与从其在糖酵解中的酶促作用开始详细阐述，这种作用影响磷酸二羟丙酮和3-磷酸甘油醛之间的平衡，到其在细胞代谢过程中更广泛的意义。文章强调了TIM中的突变如何导致代谢效率低下，从而加剧糖尿病病情。它讨论了TIM与各种细胞途径的相互作用，包括其在胰腺β细胞中对ATP敏感性钾通道的作用，这些通道对胰岛素释放至关重要。此外，我们指出了氧化应激在糖尿病中的影响，注意到TIM如何受到活性氧的影响，活性氧会破坏正常的细胞功能和胰岛素信号传导。该酶的功能还与更广泛的细胞和全身过程相关，如膜流动性和细胞信号传导途径，包括雷帕霉素靶蛋白，这些在糖尿病及其并发症的发病机制中至关重要。这篇综述强调了TIM在正常生理和病理状态下的双重作用，表明针对与TIM相关的途径可能为糖尿病的管理提供新的治疗策略。它鼓励采用综合方法来理解和治疗糖尿病，考虑到像TIM这样的生化参与者的多方面作用，它们在体内连接了代谢、氧化和调节功能。
