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Purinergic Signalling Dec 2019Purines, among most influential molecules, are reported to have essential biological function by regulating various cell types. A large number of studies have led to the... (Review)
Review
Purines, among most influential molecules, are reported to have essential biological function by regulating various cell types. A large number of studies have led to the discovery of many biological functions of the purine nucleotides such as ATP, ADP, and adenosine, as signaling molecules that engage G protein-coupled or ligand-gated ion channel receptors. The role of purines in the regulation of cellular functions at the gene or protein level has been well documented. With the advances in multiomics, including those from metabolomic and bioinformatic analyses, metabolic reprogramming was identified as a key mechanism involved in the regulation of cellular function under physiological or pathological conditions. Recent studies suggest that purines or purine-derived products contribute to important regulatory functions in many fundamental biological and pathological processes related to metabolic reprogramming. Therefore, this review summarizes the role and potential mechanism of purines in the regulation of metabolic reprogramming. In particular, the molecular mechanisms of extracellular purine- and intracellular purine-mediated metabolic regulation in various cells during disease development are discussed. In summary, our review provides an extensive resource for studying the regulatory role of purines in metabolic reprogramming and sheds light on the utilization of the corresponding peptides or proteins for disease diagnosis and therapy.
Topics: Adenosine; Adenosine Triphosphate; Animals; Humans; Molecular Targeted Therapy; Purines; Signal Transduction
PubMed: 31493132
DOI: 10.1007/s11302-019-09676-z -
Annual Review of Biochemistry Jun 2022Over the past fifteen years, we have unveiled a new mechanism by which cells achieve greater efficiency in de novo purine biosynthesis. This mechanism relies on the... (Review)
Review
Over the past fifteen years, we have unveiled a new mechanism by which cells achieve greater efficiency in de novo purine biosynthesis. This mechanism relies on the compartmentalization of de novo purine biosynthetic enzymes into a dynamic complex called the purinosome. In this review, we highlight our current understanding of the purinosome with emphasis on its biophysical properties and function and on the cellular mechanisms that regulate its assembly. We propose a model for functional purinosomes in which they consist of at least ten enzymes that localize near mitochondria and carry out de novo purine biosynthesis by metabolic channeling. We conclude by discussing challenges and opportunities associated with studying the purinosome and analogous metabolons.
Topics: Animals; Mammals; Mitochondria; Purines
PubMed: 35320684
DOI: 10.1146/annurev-biochem-032620-105728 -
Nutrients Jun 2020Infection caused by the SARS-CoV-2 coronavirus worldwide has led the World Health Organization to declare a COVID-19 pandemic. Because there is no cure or treatment for... (Review)
Review
Infection caused by the SARS-CoV-2 coronavirus worldwide has led the World Health Organization to declare a COVID-19 pandemic. Because there is no cure or treatment for this virus, it is emergingly urgent to find effective and validated methods to prevent and treat COVID-19 infection. In this context, alternatives related to nutritional therapy might help to control the infection. This narrative review proposes the importance and role of probiotics and diet as adjunct alternatives among the therapies available for the treatment of this new coronavirus. This review discusses the relationship between intestinal purine metabolism and the use of and low-purine diets, particularly in individuals with hyperuricemia, as adjuvant nutritional therapies to improve the immune system and weaken viral replication, assisting in the treatment of COVID-19. These might be promising alternatives, in addition to many others that involve adequate intake of vitamins, minerals and bioactive compounds from food.
Topics: Betacoronavirus; COVID-19; Coronavirus Infections; Diet; Humans; Immunomodulation; Lactobacillus gasseri; Pandemics; Pneumonia, Viral; Probiotics; Purines; SARS-CoV-2; Virus Replication
PubMed: 32532069
DOI: 10.3390/nu12061737 -
Progress in Neurobiology Sep 2021Despite continuous advances in understanding the underlying pathogenesis of hyperexcitable networks and lowered seizure thresholds, the treatment of epilepsy remains a... (Review)
Review
Despite continuous advances in understanding the underlying pathogenesis of hyperexcitable networks and lowered seizure thresholds, the treatment of epilepsy remains a clinical challenge. Over one third of patients remain resistant to current pharmacological interventions. Moreover, even when effective in suppressing seizures, current medications are merely symptomatic without significantly altering the course of the disease. Much effort is therefore invested in identifying new treatments with novel mechanisms of action, effective in drug-refractory epilepsy patients, and with the potential to modify disease progression. Compelling evidence has demonstrated that the purines, ATP and adenosine, are key mediators of the epileptogenic process. Extracellular ATP concentrations increase dramatically under pathological conditions, where it functions as a ligand at a host of purinergic receptors. ATP, however, also forms a substrate pool for the production of adenosine, via the action of an array of extracellular ATP degrading enzymes. ATP and adenosine have assumed largely opposite roles in coupling neuronal excitability to energy homeostasis in the brain. This review integrates and critically discusses novel findings regarding how ATP and adenosine control seizures and the development of epilepsy. This includes purine receptor P1 and P2-dependent mechanisms, release and reuptake mechanisms, extracellular and intracellular purine metabolism, and emerging receptor-independent effects of purines. Finally, possible purine-based therapeutic strategies for seizure suppression and disease modification are discussed.
Topics: Adenosine; Adenosine Triphosphate; Epilepsy; Humans; Purines; Seizures
PubMed: 34144123
DOI: 10.1016/j.pneurobio.2021.102105 -
Molecular Genetics and Metabolism Jul 2022Inborn errors of purine and pyrimidine (P/P) metabolism are under-reported and rarely mentioned in the general literature or in clinical practice, as well as in reviews... (Review)
Review
Inborn errors of purine and pyrimidine (P/P) metabolism are under-reported and rarely mentioned in the general literature or in clinical practice, as well as in reviews dedicated to other inborn errors of metabolism (IEMs). However, their diagnosis is important because genetic counseling can be provided and, in some cases, specific treatment exists that may slow or even reverse clinical signs. The purpose of this review is to provide a practical guideline on the suspicion and investigation of inborn errors of P/P metabolism. Failure of a physician to recognize the presence of these disorders may be devastating for affected infants and children because of its permanent effects in the patient, and for their parents because of implications for future offspring. Diagnosis is crucial because genetic counseling can be provided and, in some cases, specific treatment can be offered that may slow or even reverse clinical symptoms. This review highlights the risk factors in the history, the important examination findings, and the appropriate biochemical investigation of the child. Herein we describe the approach to the diagnosis of P/P disorders and emphasize clinical situations in which physicians should consider these diseases as diagnostic possibilities.
Topics: Child; Family; Humans; Infant; Purine-Pyrimidine Metabolism, Inborn Errors; Purines; Pyrimidines; Risk Factors
PubMed: 35216884
DOI: 10.1016/j.ymgme.2022.02.007 -
PloS One 2022Klebsiella pneumoniae is a bacterial pathogen that is increasingly responsible for hospital-acquired pneumonia and sepsis. Progressive development of antibiotic...
Klebsiella pneumoniae is a bacterial pathogen that is increasingly responsible for hospital-acquired pneumonia and sepsis. Progressive development of antibiotic resistance has led to higher mortality rates and creates a need for novel treatments. Because of the essential role that nucleotides play in many bacterial processes, enzymes involved in purine and pyrimidine metabolism and transport are ideal targets for the development of novel antibiotics. Herein we describe the structure of K. pneumoniae adenosine monophosphate nucleosidase (KpAmn), a purine salvage enzyme unique to bacteria, as determined by cryoelectron microscopy. The data detail a well conserved fold with a hexameric overall structure and clear density for the putative active site residues. Comparison to the crystal structures of homologous prokaryotic proteins confirms the presence of many of the conserved structural features of this protein yet reveals differences in distal loops in the absence of crystal contacts. This first cryo-EM structure of an Amn enzyme provides a basis for future structure-guided drug development and extends the accuracy of structural characterization of this family of proteins beyond this clinically relevant organism.
Topics: Humans; Klebsiella pneumoniae; Cryoelectron Microscopy; N-Glycosyl Hydrolases; Anti-Bacterial Agents; Purines; Nucleotides; Adenosine Monophosphate; Pyrimidines; Klebsiella Infections
PubMed: 36264993
DOI: 10.1371/journal.pone.0275023 -
Neurochemistry International Oct 2020Parkinson's disease (PD) is a neurodegenerative disorder that primarily affects patients over the age of 65. PD is characterized by loss of neurons in the substantia... (Review)
Review
Parkinson's disease (PD) is a neurodegenerative disorder that primarily affects patients over the age of 65. PD is characterized by loss of neurons in the substantia nigra and dopamine deficiency in the striatum. Once PD is clinically diagnosed by the observation of motor dysfunction, the disease is already in its advance stages. Consequently, there is a major push to identify clinical biomarkers that are useful for the earlier detection of PD. Using untargeted metabolomics, several research groups have identified purine molecules, and specifically urate, as important biomarkers related to PD. This review will summarize recent findings in the field of purine metabolomics and biomarker identification for PD, including in the areas of PD pathophysiology, diagnosis, prognosis and treatment. In addition, this article will summarize and examine the primary research techniques that are employed to quantify purine molecules in both experimental systems and human subjects.
Topics: Animals; Biomarkers; Brain; Humans; Mass Spectrometry; Metabolomics; Parkinson Disease; Photoelectron Spectroscopy; Positron-Emission Tomography; Purines; Uric Acid
PubMed: 32650026
DOI: 10.1016/j.neuint.2020.104793 -
Molecular Biotechnology Oct 2021Riboflavin is widely regarded as an essential nutrient that is involved in biological oxidation in vivo. In addition to preventing and treating acyl-CoA dehydrogenase... (Review)
Review
Riboflavin is widely regarded as an essential nutrient that is involved in biological oxidation in vivo. In addition to preventing and treating acyl-CoA dehydrogenase deficiency in patients with keratitis, stomatitis, and glossitis, riboflavin is also closely related to the treatment of radiation mucositis and cardiovascular disease. Chemical synthesis has been the dominant method for producing riboflavin for approximately 50 years. Nevertheless, due to the intricate synthesis process, relatively high cost, and high risk of pollution, alternative methods of chemical syntheses, such as the fermentation method, began to develop and eventually became the main methods for producing riboflavin. At present, there are three types of strains used in industrial riboflavin production: Ashbya gossypii, Candida famata, and Bacillus subtilis. Additionally, many recent studies have been conducted on Escherichia coli and Lactobacillus. Fermentation increases the yield of riboflavin using genetic engineering technology to modify and induce riboflavin production in the strain, as well as to regulate the metabolic flux of the purine pathway and pentose phosphate pathway (PP pathway), thereby optimizing the culture process. This article briefly introduces recent progress in the fermentation of riboflavin.
Topics: Bacteria; Batch Cell Culture Techniques; Fermentation; Fungi; Genetic Engineering; Humans; Pentose Phosphate Pathway; Purines; Riboflavin
PubMed: 34156642
DOI: 10.1007/s12033-021-00318-7 -
Brain Research Bulletin Sep 2019Retinal injuries and diseases are major causes of human disability involving vision impairment by the progressive and permanent loss of retinal neurons. During... (Review)
Review
Retinal injuries and diseases are major causes of human disability involving vision impairment by the progressive and permanent loss of retinal neurons. During development, assembly of this tissue entails a successive and overlapping, signal-regulated engagement of complex events that include proliferation of progenitors, neurogenesis, cell death, neurochemical differentiation and synaptogenesis. During retinal damage, several of these events are re-activated with both protective and detrimental consequences. Purines and pyrimidines, along with their metabolites are emerging as important molecules regulating both retinal development and the tissue's responses to damage. The present review provides an overview of the purinergic signaling in the developing and injured retina. Recent findings on the presence of vesicular and channel-mediated ATP release by retinal and retinal pigment epithelial cells, adenosine synthesis and release, expression of receptors and intracellular signaling pathways activated by purinergic signaling in retinal cells are reported. The pathways by which purinergic receptors modulate retinal cell proliferation, migration and death of retinal cells during development and injury are summarized. The contribution of nucleotides to the self-repair of the injured zebrafish retina is also discussed.
Topics: Adenosine; Adenosine Triphosphate; Animals; Cell Death; Cell Differentiation; Humans; Purines; Receptors, Purinergic; Receptors, Purinergic P2X; Receptors, Purinergic P2Y; Retina; Signal Transduction
PubMed: 30458250
DOI: 10.1016/j.brainresbull.2018.10.016 -
Current Medicinal Chemistry 2023Purine, one of the nucleotides, is an important substance for the metabolism and regulation of the body. Purine plays a key role not only in the composition of coenzymes...
Purine, one of the nucleotides, is an important substance for the metabolism and regulation of the body. Purine plays a key role not only in the composition of coenzymes but also in the supply of energy. Since purine was artificially synthesized, it has always been an important scaffold for respiratory diseases, cardiovascular diseases, and anti- tumor and anti-viral drugs. In addition to being widely used as competitive antagonists in the treatment of diseases, purines can be used in combination with other drugs and as precursors to benefit human life. Unfortunately, few new discoveries have been made in recent years. In this article, purine drugs in the market have been classified according to their different targets. In addition, their mechanism of action and structure-activity relationship have also been introduced. This paper provides details of the signaling pathways through which purine drugs can bind to the respective receptors on the surface of cells and cause consequent reactions within the cell, which finally affect the targeted diseases. The various receptors and biological reactions involved in the signaling for respective disease targets within the cells are discussed in detail.
Topics: Humans; Purines
PubMed: 36201270
DOI: 10.2174/0929867329666221006112458