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U.S.A."],"published-print":{"date-parts":[[2004,11,30]]},"abstract":"<jats:p>\n            The detailed molecular mechanism for the reversible inhibition of mitochondrial respiration by NO has puzzled investigators: The rate constants for the binding of NO and O\n            <jats:sub>2<\/jats:sub>\n            to the reduced binuclear center Cu\n            <jats:sub>B<\/jats:sub>\n            \/a\n            <jats:sub>3<\/jats:sub>\n            of cytochrome oxidase (COX) are similar, and NO is able to dissociate slowly from this center whereas O\n            <jats:sub>2<\/jats:sub>\n            is kinetically trapped, which altogether seems to favor the complex of COX with O\n            <jats:sub>2<\/jats:sub>\n            over the complex of COX with NO. Paradoxically, the inhibition of COX by NO is observed at high ratios of O\n            <jats:sub>2<\/jats:sub>\n            to NO (in the 40\u2013500 range) and is very fast (seconds or faster). In this work, we used simple mathematical models to investigate this paradox and other important biological questions concerning the inhibition of COX by NO. The results showed that all known features of the inhibition of COX by NO can be accounted for by a direct competition between NO and O\n            <jats:sub>2<\/jats:sub>\n            for the reduced binuclear center Cu\n            <jats:sub>B<\/jats:sub>\n            \/a\n            <jats:sub>3<\/jats:sub>\n            of COX. Besides conciliating apparently contradictory data, this work provided an explanation for the so-called excess capacity of COX by showing that the COX activity found in tissues actually is optimized to avoid an excessive inhibition of mitochondrial respiration by NO, allowing a moderate, but not excessive, overlap between the roles of NO in COX inhibition and in cellular signaling. In pathological situations such as COX-deficiency diseases and chronic inflammation, an excessive inhibition of the mitochondrial respiration is predicted.\n          <\/jats:p>","DOI":"10.1073\/pnas.0405368101","type":"journal-article","created":{"date-parts":[[2004,11,17]],"date-time":"2004-11-17T03:33:30Z","timestamp":1100662410000},"page":"16774-16779","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":152,"title":["On the mechanism and biology of cytochrome oxidase inhibition by nitric oxide"],"prefix":"10.1073","volume":"101","author":[{"given":"Fernando","family":"Antunes","sequence":"first","affiliation":[{"name":"Grupo de Bioqu\u00edmica dos Oxidantes e Antioxidantes, Centro de Qu\u00edmica e Bioqu\u00edmica, da Faculdade de Ci\u00eancias da Universidade de Lisboa, P-1749-016 Lisbon, Portugal; Instituto de Investiga\u00e7\u00e3o Cient\u00edfica Bento da Rocha Cabral, P-1250-047 Lisbon, Portugal; Laboratory of Free Radical Biology, School of Pharmacy and Biochemistry, University of Buenos Aires, C1113AAD Buenos Aires, Argentina; and Department of Molecular Pharmacology and Toxicology, School of Pharmacy, University of Southern California, Los..."}]},{"given":"Alberto","family":"Boveris","sequence":"additional","affiliation":[{"name":"Grupo de Bioqu\u00edmica dos Oxidantes e Antioxidantes, Centro de Qu\u00edmica e Bioqu\u00edmica, da Faculdade de Ci\u00eancias da Universidade de Lisboa, P-1749-016 Lisbon, Portugal; Instituto de Investiga\u00e7\u00e3o Cient\u00edfica Bento da Rocha Cabral, P-1250-047 Lisbon, Portugal; Laboratory of Free Radical Biology, School of Pharmacy and Biochemistry, University of Buenos Aires, C1113AAD Buenos Aires, Argentina; and Department of Molecular Pharmacology and Toxicology, School of Pharmacy, University of Southern California, Los..."}]},{"given":"Enrique","family":"Cadenas","sequence":"additional","affiliation":[{"name":"Grupo de Bioqu\u00edmica dos Oxidantes e Antioxidantes, Centro de Qu\u00edmica e Bioqu\u00edmica, da Faculdade de Ci\u00eancias da Universidade de Lisboa, P-1749-016 Lisbon, Portugal; Instituto de Investiga\u00e7\u00e3o Cient\u00edfica Bento da Rocha Cabral, P-1250-047 Lisbon, Portugal; Laboratory of Free Radical Biology, School of Pharmacy and Biochemistry, University of Buenos Aires, C1113AAD Buenos Aires, Argentina; and Department of Molecular Pharmacology and Toxicology, School of Pharmacy, University of Southern California, Los..."}]}],"member":"341","published-online":{"date-parts":[[2004,11,16]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(94)01290-3"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(94)00424-2"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1006\/abbi.1996.0146"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2000.tb06181.x"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm762"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(02)01112-7"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0005-2728(00)00238-3"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00176a042"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj0860541"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)54989-9"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.52.33404"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2000.3117"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3120169"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(02)01326-6"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.15.8756"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(00)01682-3"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1997.273.3.C852"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1242\/jeb.201.8.1129"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3150295"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(97)01156-3"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1006\/abbi.1995.0005"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1998.8457"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M007625200"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M211784200"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1998.274.1.C112"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9861(79)90375-8"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0005-2728(09)91009-X"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1517\/14656566.1.1.19"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0237083100"},{"key":"e_1_3_2_30_2","unstructured":"Wikstrom M. & Saraste M. 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