Formation of styrene glutathione adducts catalyzed by prostaglandin H synthase. A possible new mechanism for the formation of glutathione conjugates

Journal Article · Mon May 05 04:00:00 EDT 1986 · J. Biol. Chem.; (United States)

OSTI ID:5630953

Stock, B H; Bend, J R; Eling, T E

The metabolism of styrene by prostaglandin hydroperoxidase and horseradish peroxidase was examined. Ram seminal vesicle microsomes in the presence of arachidonic acid or hydrogen peroxide and glutathione converted styrene to glutathione adducts. Neither styrene 7,8-oxide nor styrene glycol was detected as a product in the incubation. Also, the addition of styrene 7,8-oxide and glutathione to ram seminal vesicle microsomes did not yield styrene glutathione adducts. The peroxidase-generated styrene glutathione adducts were isolated by high pressure liquid chromatography and characterized by NMR and tandem mass spectrometry as a mixture of (2R)- and (2S)-S-(2-phenyl-2-hydroxyethyl)glutathione. (1R)- and (1S)-S-(1-phenyl-2-hydroxyethyl)glutathione were not formed by the peroxidase system. The addition of phenol or aminopyrine to incubations, which greatly enhances the oxidation of glutathione to a thiyl radical by peroxidases, increased the formation of styrene glutathione adducts. We propose a new mechanism for the formation of glutathione adducts that is independent of epoxide formation but dependent on the initial oxidation of glutathione to a thiyl radical by the peroxidase, and the subsequent reaction of the thiyl radical with a suitable substrate, such as styrene.

• Research Organization: National Institute of Environmental Health Sciences, Research Triangle Park, NC
• OSTI ID: 5630953
• Journal Information: J. Biol. Chem.; (United States), Journal Name: J. Biol. Chem.; (United States) Vol. 13; ISSN JBCHA
• Country of Publication: United States
• Language: English

Related Subjects

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
400101* -- Activation
Nuclear Reaction
Radiometric & Radiochemical Procedures
550501 -- Metabolism-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALKYLATED AROMATICS
ANIMALS
ARACHIDONIC ACID
AROMATICS
BIOCHEMICAL REACTION KINETICS
CARBOXYLIC ACIDS
CELL CONSTITUENTS
CHROMATOGRAPHY
DOMESTIC ANIMALS
DRUGS
ENZYME ACTIVITY
ENZYMES
GLUTATHIONE
HYDROCARBONS
HYDROGEN COMPOUNDS
HYDROGEN PEROXIDE
KINETICS
LIQUID COLUMN CHROMATOGRAPHY
MAGNETIC RESONANCE
MAMMALS
MASS SPECTROSCOPY
METABOLISM
MICROSOMES
MONOCARBOXYLIC ACIDS
NUCLEAR MAGNETIC RESONANCE
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANOIDS
OXIDOREDUCTASES
OXYGEN COMPOUNDS
PEPTIDES
PEROXIDASES
PEROXIDES
POLYPEPTIDES
PROSTAGLANDINS
PROTEINS
RADIOPROTECTIVE SUBSTANCES
REACTION KINETICS
RESONANCE
RUMINANTS
SEPARATION PROCESSES
SHEEP
SPECTROSCOPY
STYRENE
VERTEBRATES