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Protein-protein interactions involving enzymes of the mammalian methionine and homocysteine metabolism.
Biochimie ( IF 3.3 ) Pub Date : 2020-02-24 , DOI: 10.1016/j.biochi.2020.02.015 Francisco Portillo 1 , Jesús Vázquez 2 , María A Pajares 3
Biochimie ( IF 3.3 ) Pub Date : 2020-02-24 , DOI: 10.1016/j.biochi.2020.02.015 Francisco Portillo 1 , Jesús Vázquez 2 , María A Pajares 3
Affiliation
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Enzymes of the methionine and homocysteine metabolism catalyze reactions belonging to the methionine and folate cycles and the transsulfuration pathway. The importance of the metabolites produced through these routes (e.g. S-adenosylmethionine, homocysteine) and their role in e.g. epigenetics or redox mechanisms makes their tight regulation essential for a correct cellular function. Pharmacological or pathophysiological insults induce, among others, changes in activity, oligomerization, protein levels, subcellular localization and expression of these enzymes. The abundance of these proteins in liver has made this organ the preferred system to study their regulation. Nevertheless, knowledge about their putative protein-protein interactions is limited in this and other tissues and cell types. High-throughput methods, including immunoprecipitation, affinity purification coupled to mass spectrometry and yeast two-hybrid have rendered the identification of a number of protein-protein interactions involving these enzymes in several systems. Validation by coimmunoprecipitation and/or pull-down has been made, mainly, after coexpression of bait and prey, but few of the interactions have been confirmed. Additionally, information concerning the role of these interactions in the regulation of this pathway and other cellular processes is scarce. Here, we review the current knowledge on mammalian protein-protein interactions involving methionine adenosyltransferases, S-adenosylhomocysteine hydrolase, betaine homocysteine S-methyltransferases, methionine synthase and cystathionine β-synthase, although references to data obtained in other organisms are also made. Moreover, the verified or putative implication of these interactions in the regulation of methionine and homocysteine metabolism, its interplay with other metabolic pathways and its putative link to pathophysiological processes, such as oncogenesis, is discussed.
中文翻译：
蛋白质-蛋白质相互作用涉及哺乳动物蛋氨酸的酶和高半胱氨酸代谢。
甲硫氨酸和高半胱氨酸代谢的酶催化属于甲硫氨酸和叶酸循环以及转硫途径的反应。通过这些途径产生的代谢产物（例如S-腺苷甲硫氨酸，高半胱氨酸）的重要性及其在表观遗传学或氧化还原机制中的作用，使得它们的严格调节对于正确的细胞功能至关重要。药理或病理生理学损伤可诱导活性，寡聚化，蛋白质水平，亚细胞定位和这些酶的表达等变化。肝脏中这些蛋白质的丰富性使该器官成为研究其调控的首选系统。然而，在这种以及其他组织和细胞类型中，关于它们推测的蛋白质-蛋白质相互作用的知识是有限的。高通量方法，包括免疫沉淀，与质谱联用的亲和纯化和酵母双杂交技术已经鉴定出在几个系统中涉及这些酶的许多蛋白质-蛋白质相互作用。主要在诱饵和猎物共表达后，通过共免疫沉淀和/或下拉法进行了验证，但几乎没有相互作用。另外，关于这些相互作用在该途径和其他细胞过程的调节中的作用的信息很少。在这里，我们回顾了涉及蛋氨酸腺苷基转移酶，S-腺苷同型半胱氨酸水解酶，甜菜碱同型半胱氨酸S-甲基转移酶，蛋氨酸合酶和胱硫醚β-合酶的哺乳动物蛋白质-蛋白质相互作用的当前知识，尽管也参考了从其他生物中获得的数据。此外，
更新日期：2020-02-24
中文翻译：
蛋白质-蛋白质相互作用涉及哺乳动物蛋氨酸的酶和高半胱氨酸代谢。
甲硫氨酸和高半胱氨酸代谢的酶催化属于甲硫氨酸和叶酸循环以及转硫途径的反应。通过这些途径产生的代谢产物（例如S-腺苷甲硫氨酸，高半胱氨酸）的重要性及其在表观遗传学或氧化还原机制中的作用，使得它们的严格调节对于正确的细胞功能至关重要。药理或病理生理学损伤可诱导活性，寡聚化，蛋白质水平，亚细胞定位和这些酶的表达等变化。肝脏中这些蛋白质的丰富性使该器官成为研究其调控的首选系统。然而，在这种以及其他组织和细胞类型中，关于它们推测的蛋白质-蛋白质相互作用的知识是有限的。高通量方法，包括免疫沉淀，与质谱联用的亲和纯化和酵母双杂交技术已经鉴定出在几个系统中涉及这些酶的许多蛋白质-蛋白质相互作用。主要在诱饵和猎物共表达后，通过共免疫沉淀和/或下拉法进行了验证，但几乎没有相互作用。另外，关于这些相互作用在该途径和其他细胞过程的调节中的作用的信息很少。在这里，我们回顾了涉及蛋氨酸腺苷基转移酶，S-腺苷同型半胱氨酸水解酶，甜菜碱同型半胱氨酸S-甲基转移酶，蛋氨酸合酶和胱硫醚β-合酶的哺乳动物蛋白质-蛋白质相互作用的当前知识，尽管也参考了从其他生物中获得的数据。此外，
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