Wu Di, Yang Shengqiang, Yuan Chenyang, Zhang Kejia, Tan Jiachen, Guan Kaifeng, Zeng Hong, Huang Chunjie
Institute of Reproductive Medicine, School of Medicine, Nantong University, Nantong 226001, China.
School of Basic Medicine, Youjiang Medical University for Nationalities, Baise 533000, China.
Int J Biol Macromol. 2024 Dec;282(Pt 1):136828. doi: 10.1016/j.ijbiomac.2024.136828. Epub 2024 Oct 22.
Purines are ancient metabolites with established and emerging metabolic and non-metabolic signaling attributes. The expression of purine metabolism-related genes is frequently activated in human malignancies, correlating with increased cancer aggressiveness and chemoresistance. Importantly, under certain stimulating conditions, the purine biosynthetic enzymes can assemble into a metabolon called "purinosomes" to enhance purine flux. Current evidence suggests that purine flux is regulated by a complex circuit that encompasses transcriptional, post-translational, metabolic, and association-dependent regulatory mechanisms. Furthermore, purines within the tumor microenvironment modulate cancer immunity through signaling mediated by purinergic receptors. The deregulation of purine metabolism has significant metabolic consequences, particularly hyperuricemia. Herbal-based therapeutics have emerged as valuable pharmacological interventions for the treatment of hyperuricemia by inhibiting the activity of hepatic XOD, modulating the expression of renal urate transporters, and suppressing inflammatory responses. This review summarizes recent advancements in the understanding of purine metabolism in clinically relevant malignancies and metabolic disorders. Additionally, we discuss the role of herbal interventions and the interaction between the host and gut microbiota in the regulation of purine homeostasis. This information will fuel the innovation of therapeutic strategies that target the disease-associated rewiring of purine metabolism for therapeutic applications.
嘌呤是古老的代谢产物，具有既定的和新出现的代谢及非代谢信号传导特性。嘌呤代谢相关基因的表达在人类恶性肿瘤中经常被激活，这与癌症侵袭性增加和化疗耐药性相关。重要的是，在某些刺激条件下，嘌呤生物合成酶可组装成一种称为“嘌呤体”的代谢体，以增强嘌呤通量。目前的证据表明，嘌呤通量受一个复杂回路调节，该回路包括转录、翻译后、代谢和关联依赖性调节机制。此外，肿瘤微环境中的嘌呤通过嘌呤能受体介导的信号传导调节癌症免疫。嘌呤代谢失调具有显著的代谢后果，尤其是高尿酸血症。基于草药的疗法已成为治疗高尿酸血症的有价值的药物干预措施，通过抑制肝脏黄嘌呤氧化酶的活性、调节肾脏尿酸转运蛋白的表达以及抑制炎症反应来实现。本综述总结了在临床相关恶性肿瘤和代谢紊乱中对嘌呤代谢理解方面最近的进展。此外，我们讨论了草药干预的作用以及宿主与肠道微生物群在嘌呤稳态调节中的相互作用。这些信息将推动针对疾病相关的嘌呤代谢重编程用于治疗应用的治疗策略的创新。
