PMID- 20144583
OWN - NLM
STAT- MEDLINE
DCOM- 20100526
LR  - 20161126
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1797
IP  - 5
DP  - 2010 May
TI  - Kinetic model of the inhibition of respiration by endogenous nitric oxide in 
      intact cells.
PG  - 557-65
LID - 10.1016/j.bbabio.2010.01.033 [doi]
AB  - Nitric oxide (NO) inhibits mitochondrial respiration by decreasing the apparent 
      affinity of cytochrome c oxidase (CcO) for oxygen. Using iNOS-transfected HEK 293 
      cells to achieve regulated intracellular NO production, we determined NO and O(2) 
      concentrations and mitochondrial O(2) consumption by high-resolution respirometry 
      over a range of O(2) concentrations down to nanomolar. Inhibition of respiration 
      by NO was reversible, and complete NO removal recovered cell respiration above 
      its routine reference values. Respiration was observed even at high NO 
      concentrations, and the dependence of IC(50) on [O(2)] exhibits a characteristic 
      but puzzling parabolic shape; both these features imply that CcO is protected 
      from complete inactivation by NO and are likely to be physiologically relevant. 
      We present a kinetic model of CcO inhibition by NO that efficiently predicts 
      experimentally determined respiration at physiological O(2) and NO concentrations 
      and under hypoxia, and accurately predicts the respiratory responses under 
      hyperoxia. The model invokes competitive and uncompetitive inhibition by binding 
      of NO to the reduced and oxidized forms of CcO, respectively, and suggests that 
      dissociation of NO from reduced CcO may involve its O(2)-dependent oxidation. It 
      also explains the non-linear dependence of IC(50) on O(2) concentration, and the 
      hyperbolic increase of c(50) as a function of NO concentration.
FAU - Aguirre, Enara
AU  - Aguirre E
AD  - Department of Regenerative Cardiology, Centro Nacional de Investigaciones 
      Cardiovasculares (CNIC), Melchor Fenandez Almagro 3, Madrid, Spain.
FAU - Rodriguez-Juarez, Felix
AU  - Rodriguez-Juarez F
FAU - Bellelli, Andrea
AU  - Bellelli A
FAU - Gnaiger, Erich
AU  - Gnaiger E
FAU - Cadenas, Susana
AU  - Cadenas S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100206
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
RN  - 0 (Free Radical Scavengers)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 1.14.13.39 (NOS2 protein, human)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.9.3.1 (Electron Transport Complex IV)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Cell Respiration
MH  - Cells, Cultured
MH  - Electron Transport Complex IV/*metabolism
MH  - Free Radical Scavengers/*pharmacology
MH  - Humans
MH  - Kidney/drug effects/embryology/enzymology
MH  - Kinetics
MH  - Mitochondria/drug effects/metabolism
MH  - Nitric Oxide/*physiology
MH  - Nitric Oxide Synthase Type II/genetics/metabolism
MH  - Oxidation-Reduction
MH  - Oxygen/*metabolism
MH  - Oxygen Consumption
EDAT- 2010/02/11 06:00
MHDA- 2010/05/27 06:00
CRDT- 2010/02/11 06:00
PHST- 2009/07/28 00:00 [received]
PHST- 2010/01/25 00:00 [revised]
PHST- 2010/01/27 00:00 [accepted]
PHST- 2010/02/11 06:00 [entrez]
PHST- 2010/02/11 06:00 [pubmed]
PHST- 2010/05/27 06:00 [medline]
AID - S0005-2728(10)00044-7 [pii]
AID - 10.1016/j.bbabio.2010.01.033 [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 2010 May;1797(5):557-65. doi: 10.1016/j.bbabio.2010.01.033. 
      Epub 2010 Feb 6.