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onsdag 5 juli 2023

UTP. UDP, UMP purinergisessä signaloinnissakin? Laktoosin synteesissä , galaktoosin aineenvaihdunnassa ym

UTP, UDP  sokeriaineenvaihdunnan puolella: Laktoosisynteesistä kaava: 

 https://link.springer.com/article/10.1007/s10911-021-09490-7

 

 Eri nukleotidien aineenvaihdunnalliset aitiot.  

Yksi HAKU:    Purinergic signalling?  by UTP, UDP ,UMP

5 results

Ectonucleotidases in Inflammation, Immunity, and Cancer.
Haas CB, Lovászi M, Braganhol E, Pacher P, Haskó G. J Immunol. 2021 May 1;206(9):1983-1990. doi: 10.4049/jimmunol.2001342. PMID: 33879578 Free PMC article. Review.

Abstract

Nucleoside triphosphate diphosphohydrolases (NTPDases) are a family of enzymes that hydrolyze nucleotides such as ATP, UTP, ADP, and UDP to monophosphates derivates such as AMP and UMP. The NTPDase family consists of eight enzymes, of which NTPDases 1, 2, 3, and 8 are expressed on cell membranes thereby hydrolyzing extracellular nucleotides

Cell membrane NTPDases are expressed in all tissues, in which they regulate essential physiological tissue functions such as development, blood flow, hormone secretion, and neurotransmitter release. They do so by modulating nucleotide-mediated purinergic signaling through P2 purinergic receptors. NTPDases 1, 2, 3, and 8 also play a key role during infection, inflammation, injury, and cancer. Under these conditions, NTPDases can contribute and control the pathophysiology of infectious, inflammatory diseases and cancer. 

In this review, we discuss the role of NTPDases, focusing on the less understood NTPDases 2-8, in regulating inflammation and immunity during infectious, inflammatory diseases, and cancer.

Coupling of airway ciliary activity and mucin secretion to mechanical stresses by purinergic signaling.
Davis CW, Lazarowski E. Respir Physiol Neurobiol. 2008 Nov 30;163(1-3):208-13. doi: 10.1016/j.resp.2008.05.015. Epub 2008 May 28. PMID: 18635403 Free PMC article. Review.
At rest, ATP is released onto airway surfaces at approximately 370fmol/mincm2, but only approximately 3% of released ATP is recovered in ASL. Secreted UTP meets with a similar fate. A wide variety of hydrolytic and transphosphorylating ecto-enzymes convert the triphosphate … 
 
Human Keratinocytes Respond to Extracellular UTP by Induction of Hyaluronan Synthase 2 Expression and Increased Hyaluronan Synthesis.
Jokela T, Kärnä R, Rauhala L, Bart G, Pasonen-Seppänen S, Oikari S, Tammi MI, Tammi RH. J Biol Chem. 2017 Mar 24;292(12):4861-4872. doi: 10.1074/jbc.M116.760322. Epub 2017 Feb 10. PMID: 28188289 Free PMC article.
The release of nucleotides into extracellular space is triggered by insults like wounding and ultraviolet radiation, resulting in stimulatory or inhibitory signals via plasma membrane nucleotide receptors. As similar insults are known to activate hyaluronan synthesis we ex …
 
ATP- and UTP-activated P2Y receptors differently regulate proliferation of human lung epithelial tumor cells.
Schafer R, Sedehizade F, Welte T, Reiser G. Am J Physiol Lung Cell Mol Physiol. 2003 Aug;285(2):L376-85. doi: 10.1152/ajplung.00447.2002. Epub 2003 Apr 4. PMID: 12691958 Free article.
The nucleotide efficacy profile [ATP = ADP > UDP >or= UTP > adenosine >or= 2-methylthioadenosine-5'-diphosphate, with alpha,beta-methylene adenosine 5'-triphosphate, 2',3'-O-(4-benzoylbenzoyl)adenosine 5'-triphosphate, AMP, UMP, and ATPalphaS inac … 
 
Adenine nucleotides inhibit proliferation of the human lung adenocarcinoma cell line LXF-289 by activation of nuclear factor kappaB1 and mitogen-activated protein kinase pathways.
Schäfer R, Hartig R, Sedehizade F, Welte T, Reiser G. FEBS J. 2006 Aug;273(16):3756-67. doi: 10.1111/j.1742-4658.2006.05384.x. PMID: 16911524 Free article.
ATP and ADP strongly inhibited LXF-289 cell proliferation. The nucleotide potency profile was ATP = ADP = ATPgammaS > > UTP, UDP, whereas alpha,beta-methylene-ATP, beta,gamma-methylene-ATP, 2',3'-O-(4-benzoylbenzoyl)-ATP, AMP and UMP were inactive. ...I …

Toinen HAKU:  UTP  sokeriaineenvaihdunnan  aitiossa

31 results

Liver-specific increase of UTP and UDP-sugar concentrations in rats induced by dietary vitamin B6-deficiency and its relation to complex N-glycan structures of liver membrane-proteins.
Renner AB, Rieger K, Grunow D, Zimmermann-Kordmann M, Gohlke M, Reutter W. Glycoconj J. 2007 Dec;24(9):531-41. doi: 10.1007/s10719-007-9048-x. Epub 2007 Jun 19. PMID: 17577663
In contrast to liver, the heart muscle uracil nucleotide concentrations were decreased by 40%. In kidney, the sum of UTP, UDP and UMP showed a decrease of 40%, whereas UDP-sugars were increased 1.4-fold. ...Despite the 4 to 6-fold increase of UTP
Tools and drugs for uracil nucleotide-activated P2Y receptors.
Rafehi M, Müller CE. Pharmacol Ther. 2018 Oct;190:24-80. doi: 10.1016/j.pharmthera.2018.04.002. Epub 2018 Apr 13. PMID: 29660366 Review.
 P2Y receptors (P2YRs) are a family of G protein-coupled receptors activated by extracellular nucleotides. Physiological P2YR agonists include purine and pyrimidine nucleoside di- and triphosphates, such as ATP, ADP, UTP, UDP, nucleotide sugars, and dinucleotides. Eight subtypes exist, P2Y1, P2Y2, P2Y4, P2Y6, P2Y11, P2Y12, P2Y13, and P2Y14, which represent current or potential future drug targets.
 Here we provide a comprehensive overview of ligands for the subgroup of the P2YR family that is activated by uracil nucleotides: P2Y2 (UTP, also ATP and dinucleotides), P2Y4 (UTP), P2Y6 (UDP), and P2Y14 (UDP, UDP-glucose, UDP-galactose). The physiological agonists are metabolically unstable due to their fast hydrolysis by ectonucleotidases. A number of agonists with increased potency, subtype-selectivity and/or enzymatic stability have been developed in recent years. Useful P2Y2R agonists include MRS2698 (6-01, highly selective) and PSB-1114 (6-05, increased metabolic stability). A potent and selective P2Y2R antagonist is AR-C118925 (10-01). For studies of the P2Y4R, MRS4062 (3-15) may be used as a selective agonist, while PSB-16133 (10-06) is a selective antagonist. Several potent P2Y6R agonists have been developed including 5-methoxyuridine 5'-O-((Rp)α-boranodiphosphate) (6-12), PSB-0474 (3-11), and MRS2693 (3-26). The isocyanate MRS2578 (10-08) is used as a selective P2Y6R antagonist, although its reactivity and low water-solubility are limiting. With MRS2905 (6-08), a potent and metabolically stable P2Y14R agonist is available, while PPTN (10-14) represents a potent and selective P2Y14R antagonist. The radioligand [3H]UDP can be used to label P2Y14Rs. In addition, several fluorescent probes have been developed. Uracil nucleotide-activated P2YRs show great potential as drug targets, especially in inflammation, cancer, cardiovascular and neurodegenerative diseases.
Extracellular nucleotides and nucleosides as signalling molecules.
Giuliani AL, Sarti AC, Di Virgilio F. Immunol Lett. 2019 Jan;205:16-24. doi: 10.1016/j.imlet.2018.11.006. Epub 2018 Nov 12. PMID: 30439478 Review.
Extracellular nucleotides, mainly ATP, but also ADP, UTP, UDP and UDP-sugars, adenosine, and adenine base participate in the "purinergic signalling" pathway, an ubiquitous system of cell-to-cell communication. ...
P2Y purinergic signaling in prostate cancer: Emerging insights into pathophysiology and therapy.
Khalafalla MG, Tran HN, Khalafalla FG. Biochim Biophys Acta Rev Cancer. 2022 May;1877(3):188732. doi: 10.1016/j.bbcan.2022.188732. Epub 2022 Apr 26. PMID: 35483490 Review.
Extracellular nucleotides play a central role in the growth and progression of a variety of cancer types - almost all tumor cells and immune cells express purinergic membrane receptors for extracellular nucleotides (ATP, ADP, UTP, UDP, UDP-sugar) and t …
Extracellular purines, purinergic receptors and tumor growth.
Di Virgilio F, Adinolfi E. Oncogene. 2017 Jan 19;36(3):293-303. doi: 10.1038/onc.2016.206. Epub 2016 Jun 20. PMID: 27321181 Free PMC article. Review.
Virtually, all tumor cells as well as all immune cells express plasma membrane receptors for extracellular nucleosides (adenosine) and nucleotides (ATP, ADP, UTP, UDP and sugar UDP). The tumor microenvironment is characterized by an unusually high conc …
In vivo metabolism and UTP-depleting action of 2-deoxy-2-fluoro-D-galactose.
Grün BR, Berger U, Oberdorfer F, Hull WE, Ostertag H, Keppler D. Adv Enzyme Regul. 1990;30:231-42. doi: 10.1016/0065-2571(90)90020-3. PMID: 2403033
The noninvasive in vivo 19F-NMR technique is particularly advantageous, since it allows the simultaneous analysis of all dGalF metabolites. The diversion of uridylate, due to the accumulation of UDP-2-deoxy-2-fluoro-D-hexoses, was associated with a rapid depletion of hepat …
Preparation of UDP-galacturonic acid using UDP-sugar pyrophosphorylase.
Ohashi T, Cramer N, Ishimizu T, Hase S. Anal Biochem. 2006 May 15;352(2):182-7. doi: 10.1016/j.ab.2006.02.026. Epub 2006 Mar 15. PMID: 16581011
Here we show that UDP-sugar pyrophosphorylase from Pisum sativum with a broad specificity has UDP-GalUA pyrophosphorylase activity. ...The recombinant UDP-sugar pyrophosphorylase had optimal pH of 6.0, and the apparent K(m) values for GalUA 1-ph …
Hepatic UDP-glucose and UDP-glucuronic acid synthesis rates in rats during a reduced energy state.
Dills RL, Howell SR, Klaassen CD. Drug Metab Dispos. 1987 May-Jun;15(3):281-8. PMID: 2886300
Hepatic synthesis rates of UDP-glucose and UDP-glucuronic acid were determined in rats. Two high pressure liquid chromatographic methods were developed to quantitate and isolate UTP, UDP-glucose, and UDP-glucuronic acid from perchloric acid extr … 
 
 https://pubmed.ncbi.nlm.nih.gov/14190461/
 
 https://pubmed.ncbi.nlm.nih.gov/29660366/
 

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