PMID- 17676875
OWN - NLM
STAT- MEDLINE
DCOM- 20070926
LR  - 20131121
IS  - 0006-2960 (Print)
IS  - 0006-2960 (Linking)
VI  - 46
IP  - 34
DP  - 2007 Aug 28
TI  - Horse heart myoglobin catalyzes the H2O2-dependent oxidative dehalogenation of 
      chlorophenols to DNA-binding radicals and quinones.
PG  - 9823-9
AB  - The heme-containing respiratory protein, myoglobin (Mb), best known for oxygen 
      storage, can exhibit peroxidase-like activity under conditions of oxidative 
      stress. Under such circumstances, the initially formed ferric state can react 
      with H2O2 (or other peroxides) to generate a long-lived ferryl [Fe(IV)=O] 
      Compound II (Cpd II) heme intermediate that is capable of oxidizing a variety of 
      biomolecules. In this study, the ability of Mb Cpd II to catalyze the oxidation 
      of carcinogenic halophenols is demonstrated. Specifically, 2,4,6-trichlorophenol 
      (TCP) is converted to 2,6-dichloro-1,4-benzoquinone in a H2O2-dependent process. 
      The fact that Mb Cpd II is an active oxidant in halophenol dehalogenation is 
      consistent with a traditional peroxidase order of addition of H2O2 followed by 
      TCP. With 4-chlorophenol, a dimerized product is formed, consistent with a 
      mechanism involving generation of a reactive phenoxy radical intermediate by an 
      electron transfer process. The radical nature of this process may be 
      physiologically relevant since recent studies have revealed that phenoxy radicals 
      and electrophilic quinones, specifically of the type described herein, covalently 
      bind to DNA [Dai, J., Sloat, A. L., Wright, M. W., and Manderville, R. A. (2005) 
      Chem. Res. Toxicol. 18, 771-779]. Thus, the stability of Mb Cpd II and its 
      ability to oxidize TCP may explain why such compounds are carcinogenic. 
      Furthermore, the initial rate of dehalogenation catalyzed by Mb Cpd II is nearly 
      comparable to that of the same reaction carried out by turnover of the ferric 
      state, demonstrating the potential physiological danger of this long-lived, 
      high-valent intermediate.
FAU - Osborne, Robert L
AU  - Osborne RL
AD  - Department of Chemistry and Biochemistry, University of South Carolina, Columbia, 
      South Carolina 29208, USA.
FAU - Coggins, Michael K
AU  - Coggins MK
FAU - Walla, Mike
AU  - Walla M
FAU - Dawson, John H
AU  - Dawson JH
LA  - eng
GR  - GM 26730/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20070804
PL  - United States
TA  - Biochemistry
JT  - Biochemistry
JID - 0370623
RN  - 0 (Chlorophenols)
RN  - 0 (Hemoglobins)
RN  - 0 (Myoglobin)
RN  - 0 (Quinones)
RN  - 9007-49-2 (DNA)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 1.11.1.- (DHP I dehaloperoxidase)
RN  - EC 1.11.1.- (Peroxidases)
SB  - IM
MH  - Animals
MH  - Catalysis
MH  - Chlorophenols/chemistry/*metabolism
MH  - Chromatography, Gas
MH  - DNA/*metabolism
MH  - Heart/*physiology
MH  - Hemoglobins
MH  - Horses
MH  - Hydrogen Peroxide/*pharmacology
MH  - Myoglobin/*pharmacology
MH  - Oxidation-Reduction
MH  - Peroxidases
MH  - Quinones/*chemistry
EDAT- 2007/08/07 09:00
MHDA- 2007/09/27 09:00
CRDT- 2007/08/07 09:00
PHST- 2007/08/07 09:00 [pubmed]
PHST- 2007/09/27 09:00 [medline]
PHST- 2007/08/07 09:00 [entrez]
AID - 10.1021/bi700684u [doi]
PST - ppublish
SO  - Biochemistry. 2007 Aug 28;46(34):9823-9. doi: 10.1021/bi700684u. Epub 2007 Aug 4.