- 著者
-
平塚 明
- 出版者
- The Japanese Society for the Study of Xenobiotics
- 雑誌
- 薬物動態 (ISSN:09161139)
- 巻号頁・発行日
- vol.15, no.1, pp.20-26, 2000 (Released:2007-03-29)
- 参考文献数
- 55
This article describes sources and mechanisms of formation of α, β-unsaturated aldehydes, their reactivity with respect to glutathione and amino-groups, their toxicity based on interaction with sulfhydryl and amino targets in cells, and modulation of gene expression by the aldehydes. Among the many different aldehydes generated durimg lipid peroxidation, 4-hydroxy-2 (E)-nonenal (4-HNE) is one of the major products and has been shown to have a number of adverse biological effects. All previous studies on biological and toxicological effects of 4-HNE have been carried out using its racemate. Therefore, nothing has been known of which enantiomer of the racemate is more toxic, more reactive with biomacromolecules, or more readily detoxified by glutathione S-transferase (GST) and alcohol dehydrogenase (ADH) than the other. This article also describes the first evidence for the marked enantioselectivity by 4-HNE enantiomers in the irreversible inactivation of the glycolytic enzyme, rabbit muscle glyceraldehyde-3-phosphate dehydrogenase, and in their detoxification by rat liver cytosolic GST A4-4 and ADH.