Dang Shreya, Jain Arushi, Dhanda Garima, Bhattacharya Neetu, Bhattacharya Amit, Senapati Sabyasachi
Immunogenomics Laboratory, Department of Human Genetics and Molecular Medicine, School of Health Sciences, Central University of Punjab, Bathinda, Punjab, India.
Department of Zoology, Dyal Singh College, University of Delhi, Delhi, India.
Cell Biochem Funct. 2024 Jan;42(1):e3926. doi: 10.1002/cbf.3926.
One carbon (1C) metabolism is critical for cellular viability and physiological homeostasis. Starting from its crucial involvement in purine biosynthesis to posttranslational modification of proteins, 1C metabolism contributes significantly to the development and cellular differentiation through methionine and folate cycles that are pivotal for cellular function. Genetic polymorphisms of several genes of these pathways are implicated in disease pathogenesis and drug metabolism. Metabolic products of 1C metabolism have significant roles in epigenetic modifications through DNA and histone protein methylation. Homocysteine is a product that has clinical significance in the diagnosis and prognosis of several critical illnesses, including chronic immune diseases and cancers. Regulation of the function and differentiation of immune cells, including T-cells, B-cells, macrophages, and so forth, are directly influenced by 1C metabolism and thus have direct implications in several immune disease biology. Recent research on therapeutic approaches is targeting nuclear, cytoplasmic, and mitochondrial 1C metabolism to manage and treat metabolic (i.e., type 2 diabetes), neurodegenerative (i.e., Alzheimer's disease), or immune (i.e., rheumatoid arthritis) diseases. 1C metabolism is being explored for therapeutic intervention as a common determinant for a spectrum of immune and metabolic diseases. Identifying the association or correlation between essential metabolic products of this pathway and disease onset or prognosis would further facilitate the clinical monitoring of diseases.
一碳(1C)代谢对于细胞活力和生理稳态至关重要。从其在嘌呤生物合成中的关键作用到蛋白质的翻译后修饰,1C代谢通过对细胞功能至关重要的甲硫氨酸和叶酸循环,对发育和细胞分化有显著贡献。这些途径中几个基因的遗传多态性与疾病发病机制和药物代谢有关。1C代谢的产物通过DNA和组蛋白甲基化在表观遗传修饰中发挥重要作用。同型半胱氨酸是一种在包括慢性免疫疾病和癌症在内的几种严重疾病的诊断和预后中具有临床意义的产物。包括T细胞、B细胞、巨噬细胞等在内的免疫细胞的功能和分化调节直接受1C代谢影响,因此在几种免疫疾病生物学中具有直接意义。最近关于治疗方法的研究针对细胞核、细胞质和线粒体的1C代谢来管理和治疗代谢性疾病(如2型糖尿病)、神经退行性疾病(如阿尔茨海默病)或免疫性疾病(如类风湿性关节炎)。1C代谢作为一系列免疫和代谢疾病的共同决定因素正在被探索用于治疗干预。确定该途径的必需代谢产物与疾病发作或预后之间的关联或相关性将进一步促进疾病的临床监测。