Carrera de Biología, Laboratorio de Farmacogenética, Unidad Multidisciplinaria de Investigación Experimental Zaragoza, Facultad de Estudios Superiores Zaragoza, Universidad Nacional Autónoma de México, Ciudad de México 09230, Mexico.
Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad de México, Mexico.
Rev Neurosci. 2023 Jul 7;34(8):915-932. doi: 10.1515/revneuro-2023-0039. Print 2023 Dec 15.
The transsulfuration pathway (TSP) is a metabolic pathway involving sulfur transfer from homocysteine to cysteine. Transsulfuration pathway leads to many sulfur metabolites, principally glutathione, HS, taurine, and cysteine. Key enzymes of the TSP, such as cystathionine β-synthase and cystathionine γ-lyase, are essential regulators at multiple levels in this pathway. TSP metabolites are implicated in many physiological processes in the central nervous system and other tissues. TSP is important in controlling sulfur balance and optimal cellular functions such as glutathione synthesis. Alterations in the TSP and related pathways (transmethylation and remethylation) are altered in several neurodegenerative diseases, including Parkinson's disease, suggesting their participation in the pathophysiology and progression of these diseases. In Parkinson's disease many cellular processes are comprised mainly those that regulate redox homeostasis, inflammation, reticulum endoplasmic stress, mitochondrial function, oxidative stress, and sulfur content metabolites of TSP are involved in these damage processes. Current research on the transsulfuration pathway in Parkinson's disease has primarily focused on the synthesis and function of certain metabolites, particularly glutathione. However, our understanding of the regulation of other metabolites of the transsulfuration pathway, as well as their relationships with other metabolites, and their synthesis regulation in Parkinson´s disease remain limited. Thus, this paper highlights the importance of studying the molecular dynamics in different metabolites and enzymes that affect the transsulfuration in Parkinson's disease.
转硫途径(TSP)是一种涉及从同型半胱氨酸向半胱氨酸转移硫的代谢途径。转硫途径导致许多硫代谢物,主要是谷胱甘肽、HS、牛磺酸和半胱氨酸。TSP 的关键酶,如胱硫醚β-合酶和胱硫醚γ-裂解酶,是该途径中多个水平的必需调节剂。TSP 代谢物参与中枢神经系统和其他组织中的许多生理过程。TSP 对于控制硫平衡和最佳细胞功能(如谷胱甘肽合成)很重要。TSP 和相关途径(转甲基化和再甲基化)的改变在几种神经退行性疾病中发生改变,包括帕金森病,表明它们参与这些疾病的病理生理学和进展。在帕金森病中,许多细胞过程主要由那些调节氧化还原稳态、炎症、内质网应激、线粒体功能、氧化应激和 TSP 硫代谢物的细胞内含量的过程组成。目前对帕金森病中转硫途径的研究主要集中在某些代谢物的合成和功能上,特别是谷胱甘肽。然而,我们对转硫途径的其他代谢物的调节以及它们与其他代谢物的关系及其在帕金森病中的合成调节的理解仍然有限。因此,本文强调了研究影响帕金森病中转硫作用的不同代谢物和酶的分子动力学的重要性。