Kinetics of the inhibition of mitochondrial respiration by NO

The kinetics of the inhibition of mitochondrial respiration by NO was examined in isolated mitochondria (here obtained from rat brown adipose tissue). The K i of NO for the inhibition was ∼27 nM; the IC 50 of NO increased in proportion to the square of an increase in O 2 tension. The K m of O 2 for...

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Veröffentlicht in:FEBS letters 1997-11, Vol.417 (1), p.75-80
Hauptverfasser: Koivisto, Ari, Matthias, Anita, Bronnikov, Gennady, Nedergaard, Jan
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creator Koivisto, Ari
Matthias, Anita
Bronnikov, Gennady
Nedergaard, Jan
description The kinetics of the inhibition of mitochondrial respiration by NO was examined in isolated mitochondria (here obtained from rat brown adipose tissue). The K i of NO for the inhibition was ∼27 nM; the IC 50 of NO increased in proportion to the square of an increase in O 2 tension. The K m of O 2 for respiration was ∼16 μM; in the presence of NO, the dependence of respiration on O 2 tension had a Hill coefficient of ∼2. The unusual kinetics is probably related to the ability of cytochrome c oxidase to use 2 NO or 1 O 2 as electron acceptor. The interaction between NO and O 2 in the control of respiration could be described by the formula V O 2 (O 2, NO)= V O 2 max·([O 2] 2/((16 μM·(1+[NO]/27 nM)) 2+[O 2] 2)). Thus, the kinetics is such that respiration in the presence of physiological levels of NO is very sensitive to decreasing O 2 tension.
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The K i of NO for the inhibition was ∼27 nM; the IC 50 of NO increased in proportion to the square of an increase in O 2 tension. The K m of O 2 for respiration was ∼16 μM; in the presence of NO, the dependence of respiration on O 2 tension had a Hill coefficient of ∼2. The unusual kinetics is probably related to the ability of cytochrome c oxidase to use 2 NO or 1 O 2 as electron acceptor. The interaction between NO and O 2 in the control of respiration could be described by the formula V O 2 (O 2, NO)= V O 2 max·([O 2] 2/((16 μM·(1+[NO]/27 nM)) 2+[O 2] 2)). Thus, the kinetics is such that respiration in the presence of physiological levels of NO is very sensitive to decreasing O 2 tension.</description><subject>Adipose Tissue, Brown - metabolism</subject><subject>Animals</subject><subject>Brown fat mitochondria</subject><subject>Cytochrome c oxidase</subject><subject>Female</subject><subject>Hypoxia</subject><subject>Kinetics</subject><subject>Mitochondria - drug effects</subject><subject>Mitochondria - metabolism</subject><subject>Nitric oxide</subject><subject>Nitric Oxide - pharmacology</subject><subject>Non-shivering thermogenesis</subject><subject>Oxygen</subject><subject>Oxygen - metabolism</subject><subject>Oxygen Consumption - drug effects</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><issn>0014-5793</issn><issn>1873-3468</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1997</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkMtOwzAQRS0EKqXwCZWyQrAI2E4c2wuEoGopoqILYG05zlQ1yqPYKah_Tx5Vt7Aazdw7d0YHoTHBNwST5PYNYxKHjMvoSvJrTCgTITlCQyJ4FEZxIo7R8GA5RWfef-KmF0QO0EBGkmEuhujuxZZQW-ODahXUawhsubaprW1VtpPC1pVZV2XmrM4DB35jne7EdBe8Ls_RyUrnHi72dYQ-ZtP3yTxcLJ-eJw-L0MSckjAzWZJFQBiVhiYp00wKgyOIGTBtGMGM0khoSagwWco45lLoNMWCAFDKaDRCl33uxlVfW_C1Kqw3kOe6hGrrFZdxk41bI-uNxlXeO1ipjbOFdjtFsGqxqQ6bapkoyVWHTZFmb7w_sE0LyA5be06NPu_1H5vD7n-hajZ9pJ3SCpJ34_bUfR8FDbBvC055Y6E0kFkHplZZZf949hd5xY85</recordid><startdate>19971103</startdate><enddate>19971103</enddate><creator>Koivisto, Ari</creator><creator>Matthias, Anita</creator><creator>Bronnikov, Gennady</creator><creator>Nedergaard, Jan</creator><general>Elsevier B.V</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>19971103</creationdate><title>Kinetics of the inhibition of mitochondrial respiration by NO</title><author>Koivisto, Ari ; Matthias, Anita ; Bronnikov, Gennady ; Nedergaard, Jan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4721-dcd6d3e1529c26b5a598c03e45e5ac51052238a9128cdb570798abb081ee22523</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1997</creationdate><topic>Adipose Tissue, Brown - metabolism</topic><topic>Animals</topic><topic>Brown fat mitochondria</topic><topic>Cytochrome c oxidase</topic><topic>Female</topic><topic>Hypoxia</topic><topic>Kinetics</topic><topic>Mitochondria - drug effects</topic><topic>Mitochondria - metabolism</topic><topic>Nitric oxide</topic><topic>Nitric Oxide - pharmacology</topic><topic>Non-shivering thermogenesis</topic><topic>Oxygen</topic><topic>Oxygen - metabolism</topic><topic>Oxygen Consumption - drug effects</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Koivisto, Ari</creatorcontrib><creatorcontrib>Matthias, Anita</creatorcontrib><creatorcontrib>Bronnikov, Gennady</creatorcontrib><creatorcontrib>Nedergaard, Jan</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>FEBS letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Koivisto, Ari</au><au>Matthias, Anita</au><au>Bronnikov, Gennady</au><au>Nedergaard, Jan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Kinetics of the inhibition of mitochondrial respiration by NO</atitle><jtitle>FEBS letters</jtitle><addtitle>FEBS Lett</addtitle><date>1997-11-03</date><risdate>1997</risdate><volume>417</volume><issue>1</issue><spage>75</spage><epage>80</epage><pages>75-80</pages><issn>0014-5793</issn><eissn>1873-3468</eissn><abstract>The kinetics of the inhibition of mitochondrial respiration by NO was examined in isolated mitochondria (here obtained from rat brown adipose tissue). 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subjects Adipose Tissue, Brown - metabolism
Animals
Brown fat mitochondria
Cytochrome c oxidase
Female
Hypoxia
Kinetics
Mitochondria - drug effects
Mitochondria - metabolism
Nitric oxide
Nitric Oxide - pharmacology
Non-shivering thermogenesis
Oxygen
Oxygen - metabolism
Oxygen Consumption - drug effects
Rats
Rats, Sprague-Dawley
title Kinetics of the inhibition of mitochondrial respiration by NO
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