The active site of XO is composed of a molybdopterin unit with the molybdenum
atom also coordinated by terminal oxygen (oxo), sulfur atoms and a terminalhydroxide. [6] In the reaction with xanthine to form uric acid, an oxygen atom is transferred from molybdenum to xanthine, whereby several intermediates are assumed to be involved. [7] The reformation of the active molybdenum center occurs by the addition of water. Like other known molybdenum-containing oxidoreductases, the oxygen atom introduced to the substrate by XO originates from water rather than from dioxygen (O 2 ).
Biokemistri NIGERIAN SOCIETY FOR EXPERIMENTAL BIOLOGY ISSN: 0795-8080 VOL. 17, NUM. 1, 2005, PP. 1-6 Biokemistri, Vol. 17, No. 1, June, 2005, pp. 1-6 Comparism of xanthine oxidase activities in cow and goat milks Evans C. EGWIM * , Mohammed A. VUNCHI and Patience O. EGWIM Department of Science Laboratory Technology, Federal Polytechnic, PMB 55, Bida, Niger State, Nigeria *Author to whom all correspondence should be addressed. E-mail: evansegwim@yahoo.com, Tel: 08036832178 Received 20 February 2004 Code Number: bk05001 ABSTRACT The activities of xanthine oxidase were studied in cow and goat milks. The optimum temperature and pH values were 10 o C and 7.5; and 20 o C and 7.2 - 7.4 for cow and goat milk samples respectively. The substrate effect on xanthine oxidase from both milk samples followed the popular Michealis Menten's (K m ) equation. The K m and V max were 0.86 x 10 -2 M and 3.7 Msec -1 and 4.36 x 10 -2 M and 2.0 Msec -1 . The work concludes that xanthine oxidase from cow and goat milk differs both in their basic characteristics and in the kinetic activities. Key words: xanthine oxidase. Milk, kinetic parameters INTRODUCTION Xanthine oxidase is a highly versatile enzyme that . It is a member of a group of enzymes known as molybdenum iron - sulfur flavin hydroxylases 1 . Xanthine oxidase catalyses the hydroxylation of purines, and in particular xanthine to uric acid. It is one of the major enzymes involved in the catabolism of purine nucleotides. It converts hypoxanthine to xanthine and xanthine to uric 2 . The uric acid product from xanthine oxidase catalysis contributes to the antioxidant capacity of the blood. The reduction of O 2 and H 2 O 2 in the xanthine oxidase catalysis has been proposed as a central mechanism of oxidase injury in some situations 3,4
Xanthine Oxidase has been implicated in several physiological and pathological cases. It has been shown to reduce Cyt b5 and p - 450 in mammalian hepatic microsomes under anaerobic condition 5 .It has also been shown to have antiturmor activity 6
Allopurinol, a competitive inhibitor of xanthine oxidase, has been used to treat gout patients 7 . Industrially, Xanthine oxidase been used to monitor fish freshness in fish industries 8 . Xanthine oxidase has also been immobilized to form a broke instrument for industrial and diagnostic uses 9 . It is on this background of the several applications of xanthine oxidase that the present study is designed to compare the xanthine oxidase activities from different milk samples. http://www.bioline.org.br/request?bk05001
kinetics of reaction A xanthine oxidase inhibitor is any substance that inhibits the activity of xanthine oxidase, an enzyme involved in purine metabolism. In humans, inhibition of xanthine oxidase reduces the production of uric acid, and several medications that inhibit xanthine oxidase are indicated for treatment of hyperuricemia and related medical conditions includinggout. [1] Xanthine oxidase inhibitors are being investigated for management of reperfusion injury. Xanthine oxidase inhibitors are of two kinds: purine analogues and others. Purine analogues include allopurinol, oxypurinol, [2] and tisopurine. Others include febuxostat, [3] topiroxostat, and inositols (phytic acid and myo-inositol). In experiments, numerous natural products have been found to inhibit xanthine oxidase in vitro or in model animals (mice, rats). These include three flavonoids that occur in many different fruits and vegetables: kaempferol, myricetin, and quercetin. [4] More generally, planar flavones and flavonols with a 7-hydroxyl group inhibit xanthine oxidase. [5] Anessential oil extracted from Cinnamomum osmophloeum inhibits xanthine oxidase in mice. [6] The natural product propolis from selected sources inhibits xanthine oxidase in rats; the specific substance responsible for this inhibition has not been identified, and the generality of these findings is unknown. [7] An extract of leaves of Pistacia integerrima also inhibits xanthine oxidase at a level that appears to merit further research.
Roles of the enzyme xanthine oxidase and its products. Purines and Pyrimidines Breakdown Elena Mosso 13/01/2012
Description The Enzyme. Xanthine oxydase in also called xanthine oxidoreductase. It is an enzyme which is principally involved in purine catabolism : Kegg diagram, but also in caffeine metabolism: Kegg diagram, and some xenobiothicscatabolism: Kegg diagram; xanthine oxidase is involved in xenobiothics catabolism, for example, it converts a pro drug (mercaptopurine) into the active form 6- Thioinosine-5triphosphate. Mercaptopurine is employed as an immunosuppressor in therapies against autoimmune diseases or some forms of cancer. Xanthine oxidase is an iron-molybdenum flavoprotein (FAD) containing [2Fe-2S] centres. It is distributed widely in various organs, especially in the gut and in the liver, but also in lungs, kidneys, heart, brain, plasma. The gene encoding this enzyme is localized on the short arm of chromosome 2. The enzyme oxidizes hypoxanthine to xanthine, and xanthine to uric acid, producing hydrogen peroxide. Reactions which involve the enzyme Xanthine oxydase is involved in gout pathogenesis: the accumulation of uric acid cause its precipitation in kidneys and joints (in particular in metatarso-phalangeal joints). Uric acid, in fact, forms crystals which accumulates. To solve this problem, some drugs are used. They are called xanthine oxydase inhibitors: * allopurinol is a non-selective xanthine oxidase inhibitor. It is a purinic analogue. The molecule * febuxostat is a selective xanthine oxidase inhibitor. Febuxostat: a new treatment for Hyperuricaemia in gout, 2008 Metabolic Pathways. Xanthine oxidase syntethizes uric acid and hydrogen peroxide. In gouty people, uric acid can accumulate and precipitate, leading to serious health problems. But uric acid is a molecule characterized not only by negative effects, but also it has an important role as an antioxidant, specially at low concentrations. Uric Acid as an antioxidant Uric Acid has an important role as an antioxidant, in fact in is an important peroxynitrite scavenger which protects the blood brain barrier from alterations of permeability. Moreover, it probably inhibits CNSinflammation. For this reason, it can be a protective factor against important diseases such as Multiple Sclerosis and Parkinson Disease. In fact, there is a huge evidence that PD patients have decreased levels of antioxidant enzyme activity and increased oxidative stress biomarkers. Urate has been demonstrated to reduce oxidation because it is a powerful scavengers of peroxyl radicals and hydroxyl radicals, and is able to inhibit free radical- initiated DNA damage; it can be oxidized by ROS and hemoprotein/H2O2 systems, converting them to inactive forms; moreover, it can complex with metal ions. On the other hand, uric acid can not be considerated a prognostic or diagnostic biomarker fo Parkinson Disease because it is not specific for this disease. Moreover, today it can not be used as a treatment because it carries substantial health risks such as gout, urolithiasis and possible cardiovascular diseases. Uric Acid and Oxydative Stress, 2005 Serum Uric Acid and Multiple Sclerosis , 2006(05)00146-0/abstract Role of Uric Acid in Multiple Sclerosis, 2008 Uric acid and multiple sclerosis, 2004 Uric Acid, a Peroxynitrite Scavenger, Inhibits CNS Inflammation, BloodCNS Barrier Permeability Changes, and Tissue Damage in a Mouse Model of Multiple Sclerosis , 2000 Urate: a Novel Biomarker of Parkinsons Disease, 2011 Plasma Urate and Risk of Parkinsons Disease, 2007 Other roles of xanthine oxidase. Xanthine oxidase is an enzyme involved in several pathways. Some recent studies had noticed that xanthine oxydase espression is augmented in milk and lower in colostrums; this fact can be involved in the transition from colostrum to milk production. Moreover, the enzyme can probably be involved in regulation of adipogenesis, in particular the regulation of PPAR activity. Role in adipogenesis: Xanthine Oxidoreductase is a Regulator of Adipogenesis and PPAR Activity, 2007 Role in the synthesis of colostrums and milk : Developmental changes in the milk fat globule membrane proteome during the transition from colostrum to milk, 2008(08)71181-0/abstract Role in the endothelial function. Role of Urate, Xanthine Oxidase and the Effects of Allopurinol in Vascular Oxidative Stress, 2009; Hydrogen Peroxide Regulation of Endothelial Function: Origins, Mechanisms, and Consequences, 2005; "Effect of the Treatment with Allopurinol on the Endothelial Function in Patients with Hyperuricemia, 2011": http://www.ncbi.nlm.nih.gov/pubmed/21977925 mode of regulation http://www.jbc.org/content/275/13/9369.long