Reduced synthesis of 5-aminolevulinate dehydratase in styrene-treated rats

Abstract

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.