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Cells Jan 2019Purine nucleotides are involved in a multitude of cellular processes, and the dysfunction of purine metabolism has drastic physiological and pathological consequences.... (Review)
Review
Purine nucleotides are involved in a multitude of cellular processes, and the dysfunction of purine metabolism has drastic physiological and pathological consequences. Accordingly, several genetic disorders associated with defective purine metabolism have been reported. The etiology of these diseases is poorly understood and simple model organisms, such as yeast, have proved valuable to provide a more comprehensive view of the metabolic consequences caused by the identified mutations. In this review, we present results obtained with the yeast to exemplify how a eukaryotic unicellular organism can offer highly relevant information for identifying the molecular basis of complex human diseases. Overall, purine metabolism illustrates a remarkable conservation of genes, functions and phenotypes between humans and yeast.
Topics: Humans; Metabolic Diseases; Models, Biological; Purines; Saccharomyces cerevisiae; Sequence Homology, Amino Acid
PubMed: 30658520
DOI: 10.3390/cells8010067 -
Current Opinion in Clinical Nutrition... Jul 2021Purines have several important physiological functions as part of nucleic acids and as intracellular and extracellular signaling molecules. Purine metabolites,... (Review)
Review
PURPOSE OF REVIEW
Purines have several important physiological functions as part of nucleic acids and as intracellular and extracellular signaling molecules. Purine metabolites, particularly uric acid, have been implicated in congenital and complex diseases. However, their role in complex diseases is not clear and they have both beneficial and detrimental effects on disease pathogenesis. In addition, the relationship between purines and complex diseases is affected by genetic and nutritional factors. This review presents latest findings about the relationship between purines and complex diseases and the effect of genes and nutrients on this relationship.
RECENT FINDINGS
Evidence from recent studies show strong role of purines in complex diseases. Although they are causal in only few diseases, our knowledge about their role in other diseases is still evolving. Of all the purines, uric acid is the most studied. Uric acid acts as an antioxidant as well as a prooxidant under different conditions, thus, its role in disease also varies. Other purines, adenosine and inosine have been less studied, but they have neuroprotective properties which are valuable in neurodegenerative diseases.
SUMMARY
Purines are molecules with great potential in disease pathogenesis as either metabolic markers or therapeutic targets. More studies need to be conducted to understand their relevance for complex diseases.
Topics: Humans; Nutrients; Purines; Uric Acid
PubMed: 33928921
DOI: 10.1097/MCO.0000000000000764 -
Free Radical Research Apr 2021Hydroxyl radical (HO) is the most reactive toward DNA among the reactive oxygen species (ROS) generated in aerobic organisms by cellular metabolisms. HO is generated... (Review)
Review
Hydroxyl radical (HO) is the most reactive toward DNA among the reactive oxygen species (ROS) generated in aerobic organisms by cellular metabolisms. HO is generated also by exogenous sources such as ionizing radiations. In this review we focus on the purine DNA damage by HO radicals. In particular, emphasis is given on mechanistic aspects for the various lesion formation and their interconnections. Although the majority of the purine DNA lesions like 8-oxo-purine (8-oxo-Pu) are generated by various ROS (including HO), the formation of 5',8-cyclopurine (cPu) lesions and relies exclusively on the HO attack. Methodologies generally utilized for the purine lesions quantification in biological samples are reported and critically discussed. Recent results on cPu and 8-oxo-Pu lesions quantification in various types of biological specimens associated with the cellular repair efficiency as well as with distinct pathologies are presented, providing some insights on their biological significance.
Topics: DNA Damage; Hydroxyl Radical; Purines; Reactive Oxygen Species
PubMed: 33494618
DOI: 10.1080/10715762.2021.1876855 -
Advances in Pharmacology (San Diego,... 2004
Review
Topics: Antineoplastic Agents; Cladribine; Humans; Leukemia; Pentostatin; Purines; Stem Cell Transplantation; Vidarabine
PubMed: 15464907
DOI: 10.1016/S1054-3589(04)51005-0 -
Bioorganic & Medicinal Chemistry Mar 2021Kinetin (N-furfuryladenine), a plant growth substance of the cytokinin family, has been shown to modulate aging and various age-related conditions in animal models. Here...
Kinetin (N-furfuryladenine), a plant growth substance of the cytokinin family, has been shown to modulate aging and various age-related conditions in animal models. Here we report the synthesis of kinetin isosteres with the purine ring replaced by other bicyclic heterocycles, and the biological evaluation of their activity in several in vitro models related to neurodegenerative diseases. Our findings indicate that kinetin isosteres protect Friedreich́s ataxia patient-derived fibroblasts against glutathione depletion, protect neuron-like SH-SY5Y cells from glutamate-induced oxidative damage, and correct aberrant splicing of the ELP1 gene in fibroblasts derived from a familial dysautonomia patient. Although the mechanism of action of kinetin derivatives remains unclear, our data suggest that the cytoprotective activity of some purine isosteres is mediated by their ability to reduce oxidative stress. Further, the studies of permeation across artificial membrane and model gut and blood-brain barriers indicate that the compounds are orally available and can reach central nervous system. Overall, our data demonstrate that isosteric replacement of the kinetin purine scaffold is a fruitful strategy for improving known biological activities of kinetin and discovering novel therapeutic opportunities.
Topics: Cell Survival; Cells, Cultured; Cytoprotection; Dose-Response Relationship, Drug; Humans; Kinetin; Molecular Structure; Oxidative Stress; Purines; Structure-Activity Relationship
PubMed: 33497938
DOI: 10.1016/j.bmc.2021.115993 -
Current Topics in Medicinal Chemistry 2024Numerous purine-containing compounds have undergone extensive investigation for their medical efficacy across various diseases. The swift progress in purine-based... (Review)
Review
Numerous purine-containing compounds have undergone extensive investigation for their medical efficacy across various diseases. The swift progress in purine-based medicinal chemistry has brought to light the therapeutic capabilities of purine-derived compounds in addressing challenging medical conditions. Defined by a heterocyclic ring comprising a pyrimidine ring linked with an imidazole ring, purine exhibits a diverse array of therapeutic attributes. This review systematically addresses the multifaceted potential of purine derivatives in combating various diseases, including their roles as anticancer agents, antiviral compounds (anti-herpes, anti-HIV, and anti-influenzae), autoimmune and anti-inflammatory agents, antihyperuricemic and anti-gout solutions, antimicrobial agents, antitubercular compounds, anti-leishmanial agents, and anticonvulsants. Emphasis is placed on the remarkable progress made in developing purine-based compounds, elucidating their significant target sites. The article provides a comprehensive exploration of developments in both natural and synthetic purines, offering insights into their role in managing a diverse range of illnesses. Additionally, the discussion delves into the structure-activity relationships and biological activities of the most promising purine molecules. The intriguing capabilities revealed by these purine-based scaffolds unequivocally position them at the forefront of drug candidate development. As such, this review holds potential significance for researchers actively involved in synthesizing purine-based drug candidates, providing a roadmap for the continued advancement of this promising field.
Topics: Purines; Humans; Drug Discovery; Structure-Activity Relationship; Antineoplastic Agents; Molecular Structure; Animals
PubMed: 38288806
DOI: 10.2174/0115680266290152240110074034 -
ACS Sensors Feb 2019Purine detection in the brain with fast-scan cyclic voltammetry (FSCV) at carbon-fiber microelectrodes (CFME) has become increasingly popular over the past decade;...
Purine detection in the brain with fast-scan cyclic voltammetry (FSCV) at carbon-fiber microelectrodes (CFME) has become increasingly popular over the past decade; despite the growing interest, an in-depth analysis of how purines interact with the CFME at fast-scan rates has not been investigated. Here, we show how the functional group type and placement in the purine ring modulate sensitivity, electron transfer kinetics, and adsorption on the carbon-fiber surface. Similar investigations of catecholamine interaction at CFME with FSCV have informed the development of novel catecholamine-based sensors and is needed for purine-based sensors. We tested purine bases with either amino, carbonyl, or both functional groups substituted at different positions on the ring and an unsubstituted purine. Unsubstituted purine showed very little to no interaction with the electrode surface, indicating that functional groups are important for interaction at the CFME. Purine nucleosides and nucleotides, like adenosine, guanosine, and adenosine triphosphate, are most often probed using FSCV due to their rich extracellular signaling modalities in the brain. Because of this, the extent to which the ribose and triphosphate groups affect the purine-CFME interaction was also evaluated. Amino functional groups facilitated the interaction of purine analogues with CFME more than carbonyl groups, permitting strong adsorption and high surface coverage. Ribose and triphosphate groups decreased the oxidative current and slowed the interaction at the electrode which is likely due to steric effects and electrostatic repulsion. This work provides insight into the factors that affect purine-CFME interaction and conditions to consider when developing purine-targeted sensors for FSCV.
Topics: Adenine; Adsorption; Brain; Carbon Fiber; Diffusion; Electrochemistry; Guanine; Microelectrodes; Oxidation-Reduction; Purines
PubMed: 30657307
DOI: 10.1021/acssensors.8b01504 -
Chemistry & Biology Jan 2005
Review
Topics: Adenine; Base Pairing; Crystallography, X-Ray; Guanine; Hypoxanthine; Ligands; Nucleic Acid Conformation; Purines; RNA; Regulatory Sequences, Ribonucleic Acid
PubMed: 15664510
DOI: 10.1016/j.chembiol.2005.01.002 -
Chemistry & Biodiversity Mar 2004In this review, I describe various natural manifestations of purine systems, i.e., methylated, higher-alkylated, and glycosylated forms. These comprise the purine... (Review)
Review
In this review, I describe various natural manifestations of purine systems, i.e., methylated, higher-alkylated, and glycosylated forms. These comprise the purine alkaloids, cytokines, as well as the purine nucleoside antibiotics. In part, the compounds described herein were isolated from natural sources already long ago. However, some have been reported only during the last few years. The biological activities of most of the purine derivatives are briefly described, and, in some cases, syntheses are formulated. In particular, this article introduces the main synthetic principles for the generation of the purine ring system. The last chapter describes modern preparative routes for C-alkylation and C-arylation of purines.
Topics: Alkylation; Animals; Biodiversity; Biological Products; Glycosylation; Humans; Methylation; Purines
PubMed: 17191854
DOI: 10.1002/cbdv.200490033 -
Methods in Molecular Biology (Clifton,... 2016Inborn errors of purine metabolism, either deficiencies of synthesis or catabolism pathways, lead to a wide spectrum of clinical presentations: urolithiasis (adenine...
Inborn errors of purine metabolism, either deficiencies of synthesis or catabolism pathways, lead to a wide spectrum of clinical presentations: urolithiasis (adenine phosphoribosyltransferase), primary immune deficiency (adenosine deaminase deficiency and purine nucleoside phosphorylase deficiency), severe intellectual disability, and other neurological symptoms (Lesch-Nyhan disease, adenylosuccinase deficiency, and molybdenum cofactor deficiency). A rapid quantitative purine assay was developed using UPLC-MS/MS to determine purine nucleoside and base concentrations in urine. Taking advantages of ultra performance liquid chromatography, we achieved satisfactory analyte separation and recovery with a polar T3 column in a short run time with no requirement of time-consuming sample preparation or derivatization. This targeted assay is intended for diagnosis and management of purine diseases, newborn screening follow-up of SCID, and evaluation of autism spectrum disorders.
Topics: Chromatography, High Pressure Liquid; Purines; Statistics as Topic; Tandem Mass Spectrometry; Urinalysis
PubMed: 26602134
DOI: 10.1007/978-1-4939-3182-8_24