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      Xanthine Oxidoreductase Reference Values in Platelet-Poor Plasma and Platelets in Healthy Volunteers

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          Abstract

          Introduction. Xanthine oxidoreductase (XOR) is an enzyme belonging to the class of hydroxylases. XOR is stated, inter alia, in the kidneys, liver, and small intestine as well as in leukocytes and platelets and endothelial cells of capillaries. Its main role is to participate in the conversion of hypoxanthine to xanthine and the uric acid. It occurs in two isoforms: dehydrogenase (XD) and oxidase (XO), which is considered one of the sources of reactive oxygen species. Aim of the Study. Determination of reference values of xanthine oxidoreductase activity in PPP and platelets. Materials and Methods. Study group consisted of 70 healthy volunteers. The isoform activities of xanthine oxidoreductase were determined by kinetic spectrophotometry. Results. A statistically significant difference between the activity of the XOR in PPP and platelets ( P < 0.001). The highest activity of XO was found in both PPP and blood platelets. Significant differences between the activity of the various isoforms in PPP ( P = 0.0032) and platelets ( P < 0.001) were also found. Conclusions. The healthy volunteers showed the highest activity XO (prooxidant) and the lowest XD (antioxidant), which indicates a slight oxidative stress and confirmed physiological effects of XOR.

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          Towards the physiological function of uric acid.

          Uric acid, or more correctly (at physiological pH values), its monoanion urate, is traditionally considered to be a metabolically inert end-product of purine metabolism in man, without any physiological value. However, this ubiquitous compound has proven to be a selective antioxidant, capable especially of reaction with hydroxyl radicals and hypochlorous acid, itself being converted to innocuous products (allantoin, allantoate, glyoxylate, urea, oxalate). There is now evidence for such processes not only in vitro and in isolated organs, but also in the human lung in vivo. Urate may also serve as an oxidisable cosubstrate for the enzyme cyclooxygenase. As shown for the coronary system, a major site of production of urate is the microvascular endothelium, and there is generally a net release of urate from the human myocardium in vivo. In isolated organ preparations, urate protects against reperfusion damage induced by activated granulocytes, cells known to produce a variety of radicals and oxidants. Intriguingly, urate prevents oxidative inactivation of endothelial enzymes (cyclooxygenase, angiotensin converting enzyme) and preserves the ability of the endothelium to mediate vascular dilatation in the face of oxidative stress, suggesting a particular relationship between the site of urate formation and the need for a biologically potent radical scavenger and antioxidant.
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            Xanthine oxidoreductase is central to the evolution and function of the innate immune system.

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              The physiology of endothelial xanthine oxidase: from urate catabolism to reperfusion injury to inflammatory signal transduction.

              Xanthine oxidoreductase (XOR) is a ubiquitous metalloflavoprotein that appears in two interconvertible yet functionally distinct forms: xanthine dehydrogenase (XD), which is constitutively expressed in vivo; and xanthine oxidase (XO), which is generated by the posttranslational modification of XD, either through the reversible, incremental thiol oxidation of sulfhydryl residues on XD or the irreversible proteolytic cleavage of a segment of XD, which occurs at low oxygen tension and in the presence of several proinflammatory mediators. Functionally, both XD and XO catalyze the oxidation of purines to urate. However, whereas XD requires NAD+ as an electron acceptor for these redox reactions, thereby generating the stable product NADH, XO is unable to use NAD+ as an electron acceptor, requiring instead the reduction of molecular oxygen for this purine oxidation and generating the highly reactive superoxide free radical. Nearly 100 years of study has documented the physiologic role of XD in urate catabolism. However, the rapid, posttranslational conversion of XD to the oxidant-generating form XO provides a possible physiologic mechanism for rapid, posttranslational, oxidant-mediated signaling. XO-generated reactive oxygen species (ROS) have been implicated in various clinicopathologic entities, including ischemia/reperfusion injury and multisystem organ failure. More recently, the concept of physiologic signal transduction mediated by ROS has been proposed, and the possibility of XD to XO conversion, with subsequent ROS generation, serving as the trigger of the microvascular inflammatory response in vivo has been hypothesized. This review presents the evidence and basis for this hypothesis.
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                Author and article information

                Journal
                Oxid Med Cell Longev
                Oxid Med Cell Longev
                OMCL
                Oxidative Medicine and Cellular Longevity
                Hindawi Publishing Corporation
                1942-0900
                1942-0994
                2015
                20 January 2015
                : 2015
                : 341926
                Affiliations
                Department of Laboratory Diagnostics and Molecular Medicine, Pomeranian Medical University of Szczecin, Powstancow Wielkopolskich 72, 70-111 Szczecin, Poland
                Author notes
                *Elżbieta Cecerska-Heryć: cecerskaela@ 123456wp.pl

                Academic Editor: Angel Catalá

                Author information
                http://orcid.org/0000-0001-7433-161X
                http://orcid.org/0000-0002-7308-5290
                Article
                10.1155/2015/341926
                4320863
                25688294
                80957d00-04bc-41b8-8b3e-8b95a152a388
                Copyright © 2015 Elżbieta Cecerska-Heryć et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 5 November 2014
                : 18 December 2014
                : 24 December 2014
                Categories
                Research Article

                Molecular medicine
                Molecular medicine

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