Binding of xanthine oxidase to glycosaminoglycans limits inhibition by oxypurinol.

The Journal of Biological Chemistry
Eric E KelleyMargaret M Tarpey

Abstract

Although the binding of xanthine oxidase (XO) to glycosaminoglycans (GAGs) results in significant alterations in its catalytic properties, the consequence of XO/GAG immobilization on interactions with clinically relevant inhibitors is unknown. Thus, the inhibition kinetics of oxypurinol for XO was determined using saturating concentrations of xanthine. When XO was bound to a prototypical GAG, heparin-Sepharose 6B (HS6B-XO), the rate of inactivation for uric acid formation from xanthine was less than that for XO in solution (k(inact) = 0.24 versus 0.39 min(-1)). Additionally, the overall inhibition constant (K(i)) of oxypurinol for HS6B-XO was 2-5-fold greater than for free XO (451 versus 85 nm). Univalent electron flux (O(2)(.) formation) was diminished by the binding of XO to heparin from 28.5% for free XO to 18.7% for GAG-immobilized XO. Similar to the results obtained with HS6B-XO, the binding of XO to bovine aortic endothelial cells rendered the enzyme resistant to inhibition by oxypurinol, achieving approximately 50% inhibition. These results reveal that GAG immobilization of XO in both HS6B and cell models substantially limits oxypurinol inhibition of XO, an event that has important relevance for the use of pyrazolo inhib...Continue Reading

References

May 1, 1978·Clinical Pharmacology and Therapeutics·K HandeB Chabner
Mar 1, 1977·Biochemical Pharmacology·T Spector
Aug 1, 1975·Archives of Biochemistry and Biophysics·W R WaudK V Rajagopalan
Jan 1, 1991·Annual Review of Biochemistry·L Kjellén, U Lindahl
Sep 15, 1986·Biochemical Pharmacology·T SpectorT A Krenitsky
Jan 1, 1984·Annual Review of Biochemistry·M HöökS Johansson
Jan 1, 1995·Biological & Pharmaceutical Bulletin·T FukushimaK Hirano
Apr 1, 1996·Proceedings of the Society for Experimental Biology and Medicine·Y MiyamotoH Maeda
Aug 6, 1996·Proceedings of the National Academy of Sciences of the United States of America·C R WhiteB A Freeman
Jun 7, 1996·Journal of Chromatography. B, Biomedical Applications·T YamamotoK Higashino
Feb 1, 1997·American Journal of Respiratory and Critical Care Medicine·G J QuinlanJ M Gutteridge
Oct 7, 1998·European Journal of Pharmacology·A EllisM J Rand
Jan 14, 1999·European Heart Journal·F LeyvaA J Coats
Dec 3, 1999·British Journal of Clinical Pharmacology·K TurnheimR Oberbauer
Dec 26, 2001·Proceedings of the National Academy of Sciences of the United States of America·M AslanB A Freeman
Mar 27, 2002·Methods in Enzymology·Joe M McCord
Jun 5, 2002·Atherosclerosis. Supplements·Germán CamejoGöran Bondjers
Jul 10, 2002·Circulation·Colin A J FarquharsonAllan D Struthers
Feb 11, 2003·Critical Care Medicine·S GranellDaniel Closa
Jun 11, 2003·American Journal of Respiratory and Critical Care Medicine·Vuokko L Kinnula, James D Crapo

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Citations

Mar 9, 2005·Biochemical and Biophysical Research Communications·Anna E O FisherDeclan P Naughton
Nov 1, 2008·The Journal of Biological Chemistry·Eric E KelleyMargaret M Tarpey
Jul 28, 2007·Clinical Pharmacokinetics·Richard O DayKenneth M Williams
Nov 2, 2005·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·T FujimoriT Ishida
Jan 8, 2016·Redox Biology·Celia QuijanoAndrés Trostchansky
Sep 30, 2015·Clinica Chimica Acta; International Journal of Clinical Chemistry·Thomas StablerVirginia B Kraus
Oct 21, 2015·Redox Biology·D Neil Granger, Peter R Kvietys
Oct 4, 2006·Free Radical Biology & Medicine·Stephan BaldusThomas Heitzer
Mar 17, 2006·Free Radical Biology & Medicine·Eric E KelleyMargaret M Tarpey
Oct 11, 2005·Free Radical Biology & Medicine·Stephan BaldusThomas Münzel
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Mar 5, 2013·Nitric Oxide : Biology and Chemistry·Nadiezhda Cantu-Medellin, Eric E Kelley
May 21, 2016·Naunyn-Schmiedeberg's Archives of Pharmacology·Takashi ShirakuraHiroaki Masuzaki
Nov 15, 2016·Expert Opinion on Therapeutic Patents·Ritu OjhaKunal Nepali
Apr 19, 2017·British Journal of Clinical Pharmacology·Diluk R W KannangaraRichard O Day
Apr 4, 2014·Chemical Reviews·Luisa B Maia, José J G Moura
Apr 17, 2015·Molecular Medicine·Michael C MadiganEdith Tzeng
Dec 13, 2005·American Journal of Physiology. Gastrointestinal and Liver Physiology·Robert B DormanRobert W Brock
Nov 1, 2016·Clinical Science·Richard O DayGarry G Graham
Jun 30, 2019·Oxidative Medicine and Cellular Longevity·Bartosz ProniewskiStefan Chlopicki
Aug 9, 2018·American Journal of Physiology. Endocrinology and Metabolism·Daniel B HarmonRobert M O'Doherty
Nov 18, 2019·Biochimica Et Biophysica Acta. General Subjects·Marcela Franco MineiroFlavia Carla Meotti
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