Reduced synthesis of 5-aminolevulinate dehydratase in styrene-treated rats.
5-Aminolevulinate dehydratase (porphobilinogen synthase; 5-aminolevulinate hydro-lyase, EC 4.2.1.24) preparations purified from rat liver and erythrocytes are indistinguishable in terms of molecular weight, subunit size, immunoreactivity, amino-acid composition and kinetic properties, suggesting that the enzyme from liver and erythrocytes are identical. Intraperitoneal injection of styrene to rats decreased 5-aminolevulinate dehydratase activity in both erythrocyte (to 8% of the control) and the liver (to 40% of the control). Studies utilizing polysome-directed cell-free translation indicated that hepatic synthesis of the enzyme was inhibited by styrene at the transcriptional level. In vitro addition of styrene 7,8-oxide, a major intermediate of styrene, to purified 5-aminolevulinate dehydratase resulted in a loss of immunoassayable enzyme protein to less than 1% of the untreated control. These findings suggest that the decrease in 5-aminolevulinate dehydratase caused by in vivo treatment of styrene is partially due to a transcription-dependent decrease in the enzyme synthesis, and partially to post-translational alteration of the structure of the enzyme protein.
D000818:Animals; D002474:Cell-Free System; D003864:Depression, Chemical; D004852:Epoxy Compounds / Q000494:pharmacology; D004912:Erythrocytes / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D008297:Male; D000623:Porphobilinogen Synthase / Q000096:biosynthesis* / Q000235:genetics; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger; D051381:Rats; D011919:Rats, Inbred Strains; D020058:Styrene; D013343:Styrenes / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects
D004852:Epoxy Compounds; D012333:RNA, Messenger; D013343:Styrenes; D020058:Styrene; C013690:styrene oxide; D000623:Porphobilinogen Synthase