Xanthine Oxidoreductase (xanthine + oxidoreductase)

Distribution by Scientific Domains


Selected Abstracts


Placental transfer and pharmacokinetics of allopurinol in late pregnant sows and their fetuses

JOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2008
A. J. VAN DIJK
Xanthine oxidoreductase (XOR) is a key enzyme in the evolvement of reperfusion injury resulting from birth asphyxia, a common cause of decreased viability and perinatal mortality in newborn piglets under farm conditions. At present no standard pharmacological intervention strategy is available to reduce these adverse effects of birth asphyxia. In the present study we aimed to evaluate placental transfer of allopurinol, an inhibitor of XOR. For this purpose, fetal catheterization of the jugular vein was conducted in five late pregnant sows (one fetus per sow). At 24,48 h after surgery, sows received allopurinol (15 mg/kg body weight; i.v.) and pharmacokinetics of allopurinol and its active metabolite oxypurinol were measured in both late pregnant sows and fetuses. Maternal and fetal blood samples were collected during and after allopurinol administration. Maternal Cmax values averaged 41.90 ,g/mL (allopurinol) and 3.68 ,g/mL (oxypurinol). Allopurinol crossed the placental barrier as shown by the average fetal Cmax values of 5.05 ,g/mL at 1.47 h after allopurinol administration to the sow. In only one fetus low plasma oxypurinol concentrations were found. Incubations of subcellular hepatic fractions of sows and 24-h-old piglets confirmed that allopurinol could be metabolized into oxypurinol. In conclusion, we demonstrated that allopurinol can cross the placental barrier, a prerequisite for further studies evaluating the use of allopurinol as a neuroprotective agent to reduce the adverse effects following birth asphyxia in neonatal piglets. [source]


The Physiology of Endothelial Xanthine Oxidase: From Urate Catabolism to Reperfusion Injury to Inflammatory Signal Transduction

MICROCIRCULATION, Issue 3 2002
AVEDIS MENESHIAN
ABSTRACT 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 oxidantgenerating 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. [source]


The emerging role of neuronal nitric oxide synthase in the regulation of myocardial function

EXPERIMENTAL PHYSIOLOGY, Issue 6 2006
Barbara Casadei
The recent discovery of a NOS1 gene product (i.e. a neuronal-like isoform of nitric oxide synthase or nNOS) in the mammalian left ventricular (LV) myocardium has provided a new key for the interpretation of the complex experimental evidence supporting a role for myocardial constitutive nitric oxide (NO) production in the regulation of basal and ,-badrenergic cardiac function. Importantly, nNOS gene deletion has been associated with more severe LV remodelling and functional deterioration in murine models of myocardial infarction, suggesting that nNOS-derived NO may also be involved in the myocardial response to injury. To date, the mechanisms by which nNOS influences myocardial pathophysiology remain incompletely understood. In particular, it seems over simplistic to assume that all aspects of the myocardial phenotype of nNOS knockout (nNOS,/,) mice are a direct consequence of lack of NO production from this source. Emerging data showing co-localisation of xanthine oxidoreductase (XOR) and nNOS in the sarcoplasmic reticulum of rodents, and increased XOR activity in the nNOS,/, myocardium, suggest that nNOS gene deletion may have wider implications on the myocardial redox state. Similarly, the mechanisms regulating the targeting of myocardial nNOS to different subcellular compartments and the functional consequences of intracellular nNOS trafficking have not been fully established. Whether this information could be translated into a better understanding and management of human heart failure remains the most important challenge for future investigations. [source]


Cell biology of molybdenum

BIOFACTORS, Issue 5 2009
Ralf R. Mendel
Abstract The transition element molybdenum (Mo) is an essential micronutrient that is needed as catalytically active metal during enzyme catalysis. In humans four enzymes depend on Mo: sulfite oxidase, xanthine oxidoreductase, aldehyde oxidase, and mitochondrial amidoxime reductase. In addition to these enzymes, plants harbor a fifth Mo-enzyme namely nitrate reductase. To gain biological activity and fulfill its function in enzymes, Mo has to be complexed by a pterin compound thus forming the molybdenum cofactor. This article will review the way that Mo takes from uptake into the cell, via formation of the molybdenum cofactor and its storage, up to the final insertion of the molybdenum cofactor into apometalloenzymes. 2009 International Union of Biochemistry and Molecular Biology, Inc. [source]