Document Detail

Dioxygen-dependent metabolism of nitric oxide in mammalian cells.
MedLine Citation:
PMID:  11440831     Owner:  NLM     Status:  MEDLINE    
Steady-state gradients of NO within tissues and cells are controlled by rates of NO synthesis, diffusion, and decomposition. Mammalian cells and tissues actively decompose NO. Of several cell lines examined, the human colon CaCo-2 cell produces the most robust NO consumption activity. Cellular NO metabolism is mostly O2-dependent, produces near stoichiometric NO3-, and is inhibited by the heme poisons CN-, CO (K(I) approximately 3 microM), phenylhydrazine, and NO and the flavoenzyme inhibitor diphenylene iodonium. NO consumption is saturable by O2 and NO and shows apparent K(M) values for O2 and NO of 17 and 0.2 microM, respectively. Mitochondrial respiration, O2*-, and H2O2 are neither sufficient nor necessary for O2-dependent NO metabolism by cells. The existence of an efficient mammalian heme and flavin-dependent NO dioxygenase is suggested. NO dioxygenation protects the NO-sensitive aconitases, cytochrome c oxidase, and cellular respiration from inhibition, and may serve a dual function in cells by limiting NO toxicity and by spatially coupling NO and O2 gradients.
P R Gardner; L A Martin; D Hall; A M Gardner
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Free radical biology & medicine     Volume:  31     ISSN:  0891-5849     ISO Abbreviation:  Free Radic. Biol. Med.     Publication Date:  2001 Jul 
Date Detail:
Created Date:  2001-07-06     Completed Date:  2001-12-07     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8709159     Medline TA:  Free Radic Biol Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  191-204     Citation Subset:  IM    
Division of Critical Care Medicine, Children's Hospital Medical Center, Cincinnati, OH, USA.
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MeSH Terms
Aconitate Hydratase / antagonists & inhibitors
Carbon Monoxide / pharmacology
Cell Line
Cell-Free System
Cyanides / pharmacology
Free Radicals / metabolism
Hydrogen Peroxide / metabolism
Mitochondria / drug effects,  metabolism
Nitrates / metabolism
Nitric Oxide / metabolism*
Oxygen / metabolism*,  pharmacology
Oxygenases / metabolism
Superoxides / metabolism
Reg. No./Substance:
0/Cyanides; 0/Free Radicals; 0/Nitrates; 10102-43-9/Nitric Oxide; 11062-77-4/Superoxides; 630-08-0/Carbon Monoxide; 7722-84-1/Hydrogen Peroxide; 7782-44-7/Oxygen; EC 1.13.-/Oxygenases; EC 1.14.13.-/nitric oxide dioxygenase; EC Hydratase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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