PMID- 20007376
OWN - NLM
STAT- MEDLINE
DCOM- 20100217
LR  - 20211020
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 106
IP  - 52
DP  - 2009 Dec 29
TI  - Using a functional enzyme model to understand the chemistry behind hydrogen 
      sulfide induced hibernation.
PG  - 22090-5
LID - 10.1073/pnas.0904082106 [doi]
AB  - The toxic gas H(2)S is produced by enzymes in the body. At moderate 
      concentrations, H(2)S elicits physiological effects similar to hibernation. 
      Herein, we describe experiments that imply that the phenomenon probably results 
      from reversible inhibition of the enzyme cytochrome c oxidase (CcO), which 
      reduces oxygen during respiration. A functional model of the oxygen-reducing site 
      in CcO was used to explore the effects of H(2)S during respiration. Spectroscopic 
      analyses showed that the model binds two molecules of H2S. The electro-catalytic 
      reduction of oxygen is reversibly inhibited by H(2)S concentrations similar to 
      those that induce hibernation. This phenomenon derives from a weak, reversible 
      binding of H(2)S to the Fe(II) porphyrin, which mimics heme a(3) in CcO's active 
      site. No inhibition of CcO is detected at lower H(2)S concentrations. 
      Nevertheless, at lower concentrations, H(2)S could have other biological effects 
      on CcO. For example, H(2)S rapidly reduces Fe(III) and Cu(II) in both the 
      oxidized form of this functional model and in CcO itself. H(2)S also reduces 
      CcO's biological reductant, cytochrome c, which normally derives its reducing 
      equivalents from food metabolism. Consequently, it is speculated that H(2)S might 
      also serve as a source of electrons during periods of hibernation when food 
      supplies are low.
FAU - Collman, James P
AU  - Collman JP
AD  - Department of Chemistry, Stanford University, Stanford, CA 94305, USA. 
      jpc@stanford.edu
FAU - Ghosh, Somdatta
AU  - Ghosh S
FAU - Dey, Abhishek
AU  - Dey A
FAU - Decreau, Richard A
AU  - Decreau RA
LA  - eng
GR  - R01 GM017880/GM/NIGMS NIH HHS/United States
GR  - GM-17880-38/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20091209
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - E1UOL152H7 (Iron)
RN  - EC 1.9.3.1 (Electron Transport Complex IV)
RN  - YY9FVM7NSN (Hydrogen Sulfide)
SB  - IM
MH  - Animals
MH  - Catalytic Domain
MH  - Electrochemistry
MH  - Electron Spin Resonance Spectroscopy
MH  - Electron Transport Complex IV/*antagonists & inhibitors/chemistry/metabolism
MH  - Hibernation/drug effects/*physiology
MH  - Hydrogen Sulfide/metabolism/*pharmacology
MH  - Iron/chemistry
MH  - Models, Biological
MH  - Models, Molecular
MH  - Nuclear Magnetic Resonance, Biomolecular
MH  - Spectroscopy, Fourier Transform Infrared
PMC - PMC2799705
COIS- The authors declare no conflict of interest.
EDAT- 2009/12/17 06:00
MHDA- 2010/02/18 06:00
PMCR- 2010/06/29
CRDT- 2009/12/17 06:00
PHST- 2009/12/17 06:00 [entrez]
PHST- 2009/12/17 06:00 [pubmed]
PHST- 2010/02/18 06:00 [medline]
PHST- 2010/06/29 00:00 [pmc-release]
AID - 0904082106 [pii]
AID - 8150 [pii]
AID - 10.1073/pnas.0904082106 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2009 Dec 29;106(52):22090-5. doi: 
      10.1073/pnas.0904082106. Epub 2009 Dec 9.