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Frontiers in Endocrinology 2020Non-shivering thermogenesis in mammalian brown adipose tissue is a powerful mechanism to defend normothermia in cold climates. To minimize the loss of chemical energy,... (Review)
Review
Non-shivering thermogenesis in mammalian brown adipose tissue is a powerful mechanism to defend normothermia in cold climates. To minimize the loss of chemical energy, the central functional component, mitochondrial uncoupling protein 1, UCP1, must be tightly regulated. The canonical pathway of UCP1 activation includes lipolytic release of free fatty acids in response to an adrenergic signal. Activating fatty acids overcome constitutive inhibition of UCP1 by the di- and triphosphate forms of purine nucleotides, i.e., ATP, ADP, GTP, and GDP. Cellular concentrations of inhibitory, free nucleotides are subject to significant, adrenergically induced alterations. The regulatory components involved may constitute novel drug targets to manipulate brown fat thermogenesis and thereby organismic energy balance. We here review evidence for and against a dominant role of nucleotides in thermogenic control, describe conceptual routes to endogenously and pharmacologically alter free nucleotide pool size, speculate on a signaling role of degradation products released from active brown fat, and highlight gaps in our understanding of signaling and metabolic pathways involved.
Topics: Adipocytes, Brown; Adipose Tissue, Brown; Animals; Energy Metabolism; Humans; Mammals; Oxygen Consumption; Purine Nucleotides; Thermogenesis
PubMed: 32210919
DOI: 10.3389/fendo.2020.00118 -
Biochemical Society Transactions Aug 1988
Review
Topics: Animals; Blood Vessels; Muscle Tonus; Muscle, Smooth, Vascular; Purine Nucleotides; Receptors, Purinergic
PubMed: 3061848
DOI: 10.1042/bst0160480 -
Journal of Renal Nutrition : the... Sep 2010There are almost 100 different substances called uremic toxins. In this study, we analyze all findings concerning the new family of uremic compounds--nicotinamide end... (Review)
Review
There are almost 100 different substances called uremic toxins. In this study, we analyze all findings concerning the new family of uremic compounds--nicotinamide end products: N-methyl-2-pyridone-5-carboxamide (Met2PY), N-methyl-4-pyridone-5-carboxamide, newly described 4-pyridone-3-carboxamide-1-beta-D-ribonucleoside (4PYR) and 4-pyridone-3-carboxamide-1-beta-D-ribonucleoside triphosphate (4PYTP). After few years of studies, we have found that these substances have higher plasma concentration in patients with chronic renal failure (CRF) in comparison with the healthy population. We noted a 40-fold increase in plasma 4PYR concentration in patients with CRF. This increment correlates significantly with the decline of kidney function measured as an increase of serum creatinine concentration and decrease of estimated glomerular filtration rate. Tested compounds are present and measurable in physiological fluids and tissues. We found higher saliva Met2PY concentration in patients with CRF in comparison with controls. Saliva Met2PY correlated negatively with estimated glomerular filtration rate and positively with serum creatinine concentration. One-third of studied group had higher concentration of Met2PY in the saliva than in plasma, and this segment of patients may be called as "good excretors." In rats with experimental CRF, we found that both Met2PY and N-methyl-4-pyridone-5-carboxamide accumulated in selected tissues. We also demonstrated formation of 4PYTP in intact human erythrocytes during incubation with the precursor 4PYR. Incubation with 4PYR leads to lowering concentration of adenosine-5'-triphosphate. 4PYTP formation may be a way to remove 4PYR from the circulation and save adenosine-5'-triphosphate depletion. Summarizing, end products of the nicotinamide family are members of uremic toxins; however, exact pathophysiological role of these compounds in the development of uremic syndrome needs further studies.
Topics: Animals; Creatinine; Glomerular Filtration Rate; Humans; Kidney Failure, Chronic; Nucleosides; Nucleotides; Purine Nucleotides; Pyridones; Saliva; Uremia
PubMed: 20797575
DOI: 10.1053/j.jrn.2010.05.003 -
Journal of Medicinal Chemistry Apr 2019Cluster of differentiation 73 (CD73) converts adenosine 5'-monophosphate to immunosuppressive adenosine, and its inhibition was proposed as a new strategy for cancer...
Cluster of differentiation 73 (CD73) converts adenosine 5'-monophosphate to immunosuppressive adenosine, and its inhibition was proposed as a new strategy for cancer treatment. We synthesized 5'- O-[(phosphonomethyl)phosphonic acid] derivatives of purine and pyrimidine nucleosides, which represent nucleoside diphosphate analogues, and compared their CD73 inhibitory potencies. In the adenine series, most ribose modifications and 1-deaza and 3-deaza were detrimental, but 7-deaza was tolerated. Uracil substitution with N-methyl, but not larger groups, or 2-thio, was tolerated. 1,2-Diphosphono-ethyl modifications were not tolerated. N-(Aryl)alkyloxy-cytosine derivatives, especially with bulky benzyloxy substituents, showed increased potency. Among the most potent inhibitors were the 5'- O-[(phosphonomethyl)phosphonic acid] derivatives of 5-fluorouridine (4l), N-benzoyl-cytidine (7f), N-[ O-(4-benzyloxy)]-cytidine (9h), and N-[ O-(4-naphth-2-ylmethyloxy)]-cytidine (9e) ( K values 5-10 nM at human CD73). Selected compounds tested at the two uridine diphosphate-activated P2Y receptor subtypes showed high CD73 selectivity, especially those with large nucleobase substituents. These nucleotide analogues are among the most potent CD73 inhibitors reported and may be considered for development as parenteral drugs.
Topics: 5'-Nucleotidase; Animals; Enzyme Inhibitors; GPI-Linked Proteins; Humans; Purine Nucleotides; Pyrimidine Nucleotides; Rats; Structure-Activity Relationship
PubMed: 30895781
DOI: 10.1021/acs.jmedchem.9b00164 -
The International Journal of... 1988
Review
Topics: Animals; Cell Compartmentation; Cell Membrane; Cell Nucleus; Purine Nucleotides; Pyrimidine Nucleotides
PubMed: 3073978
DOI: 10.1016/0020-711x(88)90248-0 -
Nucleosides, Nucleotides & Nucleic Acids 2020Dietary purine restrictions are recommended for patients with hyperuricemia and gout. While measuring the purine contents of various foods in our laboratory using...
Measurement of the total purine contents and free nucleosides, nucleotides, and purine bases composition in Japanese anchovies () using high-performance liquid chromatography with UV detection.
Dietary purine restrictions are recommended for patients with hyperuricemia and gout. While measuring the purine contents of various foods in our laboratory using high-performance liquid chromatography (HPLC), we observed and reported changes in purine composition. In this study, we measured the total purine content and free purine of raw anchovies as well as after fermentation, using two methods by HPLC. Method 1 involved acid hydrolysis of all purines, such as nucleic acids and nucleotides, to form four corresponding purine bases. Method 2, which is a non-hydrolysis method, is used to measure the amount of free purines (nucleotide, nucleoside, purine base). As a result of method 1, after fermentation, adenine-related and hypoxanthine-related purines and the total purine levels decreased significantly. Regardless of being raw or fermented, each anchovy contained mainly hypoxanthine- and guanine-related purines. Among the hypoxanthine-related purines, the results of method 2 revealed that the raw anchovies contained a lot of inosine monophosphate (IMP), while after fermentation contained more inosine. In guanine-related and adenine-related purines, those nucleotides decreased by fermentation and nucleosides and bases increased. Measurements of free purines revealed that those reductions after fermentation observed in method 1 were derived from decreased nucleotides. These results indicate that purines are affected by the fermentation bacteria and period.
Topics: Animals; Chromatography, High Pressure Liquid; Fermentation; Fishes; Food Analysis; Purine Nucleosides; Purine Nucleotides; Seafood; Spectrophotometry, Ultraviolet
PubMed: 33231138
DOI: 10.1080/15257770.2020.1809674 -
Nutrition (Burbank, Los Angeles County,... 1995There is a growing body of research that demonstrates a role for dietary nucleotides, the building blocks of RNA and DNA, during intestinal development, turnover, and... (Review)
Review
There is a growing body of research that demonstrates a role for dietary nucleotides, the building blocks of RNA and DNA, during intestinal development, turnover, and repair. There is evidence that the effects of purine nucleotides may be mediated through intestinal gene transcription and, more specifically, through the action of transcription factors that, at least sometimes, are directly related to nutrition. Some of the suggested specific roles for dietary nucleotides include the enhancement of the normal host defense system, effects on neonatal lipid metabolism, and influence on iron bioavailability. This review focuses on the potential role of dietary (purine) nucleotides in the maintenance of intestinal integrity and reviews potential mechanisms for these effects.
Topics: Animals; Base Sequence; DNA; Diet; Digestive System; Gene Expression Regulation, Developmental; Humans; Hypoxanthine Phosphoribosyltransferase; Purine Nucleotides
PubMed: 8719129
DOI: No ID Found -
The Journal of Nutrition Jan 1994Nucleotides are phosphate esters of nucleosides that contain a sugar linked through a glycosidic linkage with purine and pyrimidine bases. Purine and pyrimidine... (Review)
Review
Nucleotides are phosphate esters of nucleosides that contain a sugar linked through a glycosidic linkage with purine and pyrimidine bases. Purine and pyrimidine nucleotides are major components of the cells that make up the monomeric units of DNA and RNA, and they function in all cellular processes. Biosynthesis, interconversion, catabolism and other aspects of nucleotide metabolism, along with various cellular roles of nucleotides, will be discussed, and the possible use of dietary sources of preformed purines and pyrimidines will be considered.
Topics: Animals; Humans; Purine Nucleotides; Pyrimidine Nucleotides
PubMed: 8283301
DOI: 10.1093/jn/124.suppl_1.124S -
Cold Spring Harbor Perspectives in... Jul 2021
Review
Topics: Animals; Humans; Nucleosides; Purine Nucleotides; Pyrimidine Nucleotides; Signal Transduction
PubMed: 34210662
DOI: 10.1101/cshperspect.a040592 -
Drug Metabolism Reviews 1977
Review
Topics: Antimetabolites; Biodegradation, Environmental; Caffeine; Methylation; Plants; Purine Nucleotides; Purines
PubMed: 344021
DOI: 10.3109/03602537708997480