Inhibition of δ-aminolevulinate dehydratase in trichloroethylene-exposed rats, and the effects on heme regulation

Hiroyoshi Fujita, Akio Koizumi, Masayuki Yamamoto, Miho Kumai, Tetsuo Sadamoto, Masayuki Ikeda

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

Abstract

A pronounced and irreversible depression of the erythroid and liver δ-aminolevulinate dehydratase (porphobilinogen synthase; 5-aminolevulinate hydro-lyase, EC 4.2.1.24) activity was observed in rats exposed to trichloroethylene, a widely used solvent. The depression could not be restored after the treatment with dithiothreitol and zinc; however, radioimmunoassay of δ-aminolevulinate dehydratase indicated that trichloroethylene exposure did not essentially decrease the amount of enzyme. The depression of the enzyme activity thus proved to be due to a reduction in the enzyme amount but to enzyme inhibition. The purified holoenzyme (fully activated δ-aminolevulinate dehydratase with 1 atom zinc per subunit) and apoenzyme (fully activated enzyme with the remaining zinc less than 0.1 atom per subunit) were prepared to investigate the in vitro inhibition of the enzyme by trichloroethylene. Incubation with trichloroethylene did not inhibit the holoenzyme, but inhibited the apoenzyme dose-dependently. Trichloroethylene inhibited the holoenzyme when incubated with the mixed function oxidase system. The in vitro experiments reported here indicate two mechanisms of the enzyme inhibition by trichloroethylene. In the liver of rats exposed to trichloroethylene, cytochrome P-450 concentration and heme saturation of tryptophan pyrrolase (EC 1.13.11.11) are reduced; in addition, the activity of δ-aminolevulinate synthase (EC 2.3.1.37) increased. After exposure to trichloroethylene at 2.14 g/m3, urinary δ-aminolevulinic acid increased to 142% of the control, while the excretion of coproporphyrin was reduced to 19.6% of the control.

Original languageEnglish
Pages (from-to)1-10
Number of pages10
JournalBBA - General Subjects
Volume800
Issue number1
DOIs
Publication statusPublished - 1984 Jul 16

Keywords

  • (Rat liver)
  • Heme regulation
  • Trichloroethylene exposure
  • δ-Aminolevulinate dehydratase

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

Fingerprint Dive into the research topics of 'Inhibition of δ-aminolevulinate dehydratase in trichloroethylene-exposed rats, and the effects on heme regulation'. Together they form a unique fingerprint.

Cite this