Emerging Role of Purine Metabolizing Enzymes in Brain Function and Tumors

Abstract

The growing evidence of the involvement of purine compounds in signaling, of nucleotide imbalance in tumorigenesis, the discovery of purinosome and its regulation, cast new light on purine metabolism, indicating that well known biochemical pathways may still surprise. Adenosine deaminase is important not only to preserve functionality of immune system but also to ensure a correct development and function of central nervous system, probably because its activity regulates the extracellular concentration of adenosine and therefore its function in brain. A lot of work has been done on extracellular 5′-nucleotidase and its involvement in the purinergic signaling, but also intracellular nucleotidases, which regulate the purine nucleotide homeostasis, play unexpected roles, not only in tumorigenesis but also in brain function. Hypoxanthine guanine phosphoribosyl transferase (HPRT) appears to have a role in the purinosome formation and, therefore, in the regulation of purine synthesis rate during cell cycle with implications in brain development and tumors. The final product of purine catabolism, uric acid, also plays a recently highlighted novel role. In this review, we discuss the molecular mechanisms underlying the pathological manifestations of purine dysmetabolisms, focusing on the newly described/hypothesized roles of cytosolic 5′-nucleotidase II, adenosine kinase, adenosine deaminase, HPRT, and xanthine oxidase.

What does your cell really do? Model-based assessment of mammalian cells metabolic functionalities using omics data

“…We further used these identified tasks to investigate their expression patterns (i.e., percentage of patient samples associated with an active task and related median score) across the groups of patients presenting or not a positive diagnosis for Alzheimer's disease. Very distinctive median score distribution depending on the Alzheimer's diagnosis are observed for 4 tasks previously highlighted in the literature as being implicated in the Alzheimer's disease ( Figure 6E-G): the synthesis of Tn antigen 40,41 (glycoprotein N-acetylgalactosamine), the synthesis of tetrahydrofolate 42 and the salvage of IMP and GMP 43 . While the other metabolic tasks identified do not present distinctive patterns at the level of the median score distribution, we can observe that healthy subjects often present a higher percentage of samples for which these tasks are active (Supplementary Figure 5).…”

Зміни Метаболізму Пуринів При Кістково-Суглобовій Формі Раку Легені

“…Остается недостаточно изученной роль нарушений метаболизма пуринов в процессах канцерогенеза, а их клиническое значение требует уточнения [8]. Было установлено, что гиперурикемия является фактором риска развития и последующего тяжелого течения РЛ [9,10].…”

Investigation on the Characteristic Components of Dahuang Zhechong Pill Based on High-Performance Liquid Chromatography (HPLC) Fingerprint

“…9 At the same time, increasing evidence suggests that purine compounds are involved in regulating the purine nucleotide homeostasis, playing unexpected roles in tumorigenesis, which may provide a novel treatment for cancer. 10,11 Hypoxanthine is a type of alkaloid and is considered as an important pharmacodynamic substance in TCM. 12 The generation of free radicals through oxidative metabolism is considered as one of the mechanisms of its pharmacological action.…”