Reaction of (E,E)-muconaldehyde and its aldehydic metabolites, (E,E)-6-oxohexadienoic acid and (E,E)-6-hydroxyhexa-2,4-dienal, with glutathione

Journal Article · · Chemical Research in Toxicology; (United States)

DOI:https://doi.org/10.1021/tx00034a029· OSTI ID:7060384

Kline, S A; Xiang, Q; Goldstein, B D; Witz, G ^[1]

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1. Robert Wood Johnson Medical School, Piscataway, NJ (United States) Environmental and Occupational Health Sciences Institute, Piscataway, NJ (United States)

(E,E)-Muconaldehyde (muconaldehyde) has been identified as a hematotoxic metabolite of benzene in vitro. It is metabolized in mouse liver cytosol to oxidized and reduced derivatives including the [alpha],[beta]-unsaturated aldehydes (E,E)-6-oxohexadienoic acid and (E,E)-6-hydroxy-2,4-hexadienal. In this study we have synthesized the aldehydic metabolites of muconaldehyde. The reaction of glutathione with muconaldehyde and its aldehyde metabolites was investigated. Reactions were bimolecular and stoichiometric and aldehyde and glutathione in the initial phases. Second-order rate constants were determined, and the rates were in the order muconaldehyde > (E,E)-6-hydroxy-2,4-hexadienal > (E,E)-6-oxohexadienoic acid. Further investigation of the reaction of muconaldehyde with glutathione showed that the bimolecular reaction is reversible but the initial product decomposed irreversibly to two or more products, one of which had a red-shifted UV spectrum. Rate constants for these subsequent reactions were determined. The results are discussed in terms of the toxicity of muconaldehyde at tissues distal from the liver, where it is believed to be formed from the metabolism of benzene. 24 refs., 3 figs., 1 tab.

• OSTI ID: 7060384
• Journal Information: Chemical Research in Toxicology; (United States), Journal Name: Chemical Research in Toxicology; (United States) Vol. 6:4; ISSN 0893-228X; ISSN CRTOEC
• Country of Publication: United States
• Language: English

Related Subjects

550200 -- Biochemistry
560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALDEHYDES
AROMATICS
BENZENE
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL PATHWAYS
BODY
DIGESTIVE SYSTEM
DRUGS
GLANDS
GLUTATHIONE
HYDROCARBONS
KINETICS
LIVER
METABOLIC ACTIVATION
METABOLITES
ORGANIC COMPOUNDS
ORGANS
PEPTIDES
POLYPEPTIDES
PROTEINS
RADIOPROTECTIVE SUBSTANCES
REACTION KINETICS
TOXICITY