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Title: Uncoupling of oxidative phosphorylation in rat liver mitochondria by chloroethanols

Conference · · FASEB Journal (Federation of American Societies for Experimental Biology); (United States)
OSTI ID:5373738
; ;  [1]
  1. Univ. of Texas Medical Branch, Galveston (United States)

Chloroethanols are toxic chemicals used in the industry and also formed as a result of the metabolism of several widely used halogenated hydrocarbons. The effect of 2-chloroethanol (CE), 2,2-dichloroethanol (DCE) and 2,2,2-trichloroethanol (TCE) on rat liver mitochondrial respiration was studied. Rat liver mitochondria were prepared in a mitochondrial isolation medium consisting of 250 mM sucrose, 10 mM Tris-HCl and 1 mM EDTA. Respiration of the mitochondrial suspension was determined with an oxygen electrode at 25C and the polarographic buffer consisted of 250 mM mannitol, 10 mM KCl, 10 mM K{sub 2}HPO{sub 4}, 5 mM MgCl{sub 2}, 0.2 mM EDTA and 10 mM Tris-HCl. With succinate as the respiratory substrate and using chloroethanols, CE stimulated respiration by 28.2 {plus minus} 6.5% and DCE by 202.7 {plus minus} 8.2% while TCE inhibited mitochondrial respiration. The effect of change in the concentration of chloroethanols on mitochondrial respiration was also studied. CE showed maximum stimulation at 600 mM, DCE at 150 mM and TCE at 30 mM. Respiratory stimulation was independent of mitochondrial protein concentration. Chloroethanols inhibited mitochondrial respiration when glutamate-malate was used as the respiratory substrate. Estimation of adenosine triphosphate (ATP) generation showed that chloroethanols inhibited the synthesis of ATP. These results indicate that chloroethanols stimulate mitochondrial respiration by uncoupling oxidative phosphorylation and that the uncoupling potency is proportional to the extent of chlorination.

OSTI ID:
5373738
Report Number(s):
CONF-9104107-; CODEN: FAJOE
Journal Information:
FASEB Journal (Federation of American Societies for Experimental Biology); (United States), Vol. 5:4; Conference: 75. annual meeting of the Federation of American Societies for Experimental Biology (FASEB), Atlanta, GA (United States), 21-25 Apr 1991; ISSN 0892-6638
Country of Publication:
United States
Language:
English