Reaction of glutathione with a free radical metabolite of carbon tetrachloride
- National Institute of Environmental Health Sciences, Research Triangle Park, NC (USA)
Carbon tetrachloride and bromotrichloromethane are both metabolized by cytochrome P-450 in the presence of phenyl-N-t-butyl nitrone (PBN) to the PBN/trichloromethyl (PBN/.CCl3) and the PBN carbon dioxide anion (PBN/.CO2-) radical adducts in the liver. The formation of the latter but not the former species in perfused liver was reduced markedly by prior depletion of hepatic glutathione with either diethyl maleate or buthionine sulfoximine treatments. In microsomal incubations, the PBN/.CO2- radical adduct was detected only upon the addition of cytosol. In microsomal incubations containing PBN, CCl4, and GSH, but no added cytosol, a novel radical adduct with distinctive coupling constants was detected. This radical adduct's ESR spectrum exhibited 13C isotope effects when it was formed in an incubation containing 13CCl4 or Br13CCl3. The presence of GSH in the radical adduct is postulated based on the radical adduct's hydrophilicity and slow rate of rotation in solution. The detection of this new radical adduct, PBN/(GSH-.CCl3), establishes the reaction of GSH with a CCl4-derived free radical as a significant event in the metabolism of CBrCl3 and CCl4. The cytosolic conversion of PBN/(GSH-.CCl3) into PBN/.CO2- has been demonstrated and characterizes the PBN/.CO2- radical adduct as the product of metabolism of PBN/(GSH-.CCl3), a primary radical adduct. Thus, it is concluded that GSH rather than oxygen is obligatory for the formation of PBN/.CO2- from .CCl3 in intact cells.
- OSTI ID:
- 6967475
- Journal Information:
- Molecular Pharmacology; (USA), Journal Name: Molecular Pharmacology; (USA) Vol. 37:3; ISSN 0026-895X; ISSN MOPMA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
BIOCHEMICAL REACTION KINETICS
BIOSYNTHESIS
BODY
CARBON 13
CARBON COMPOUNDS
CARBON DIOXIDE
CARBON ISOTOPES
CARBON OXIDES
CARBON TETRACHLORIDE
CELL CONSTITUENTS
CHALCOGENIDES
CHLORINATED ALIPHATIC HYDROCARBONS
DIGESTIVE SYSTEM
DRUGS
ELECTRON SPIN RESONANCE
ENZYME ACTIVITY
ENZYMES
EVEN-ODD NUCLEI
GLANDS
GLUTATHIONE
HALOGENATED ALIPHATIC HYDROCARBONS
IN VITRO
ISOTOPE EFFECTS
ISOTOPES
KINETICS
LIGHT NUCLEI
LIVER
MAGNETIC RESONANCE
MAMMALS
METABOLISM
MICROSOMES
MIXED-FUNCTION OXIDASES
NUCLEI
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANOIDS
ORGANS
OXIDES
OXIDOREDUCTASES
OXYGEN COMPOUNDS
OXYGENASES
PEPTIDES
PERFUSED ORGANS
POLYPEPTIDES
PROTEINS
RADICALS
RADIOPROTECTIVE SUBSTANCES
RATS
REACTION KINETICS
RESONANCE
RIBOSOMES
RODENTS
STABLE ISOTOPES
SYNTHESIS
VERTEBRATES