Abstract
1. Paraquat and diquat produce only a slight increase in the oxygen uptake of rat liver mitochondria, and it is likely that they do not penetrate the mitochondrial membrane. 2. In mitochondrial fragments inhibited by antimycin A or by Amytal, both substances stimulate oxygen uptake with NADH or β-hydroxybutyrate as substrate but not with succinate. The NADH dehydrogenase of the respiratory chain appears to be involved, at a site only partially inhibited by Amytal. 3. An NADPH oxidase activity is stimulated in rat liver microsomes by diquat, and to a smaller extent by paraquat; diquat also causes an NADH oxidase activity to develop. The effect is not inhibited by carbon monoxide or p-chloromercuribenzoate, and it is probable that a flavoprotein is involved by a mechanism not requiring thiol groups. 4. One molecule of oxygen can oxidize two molecules of NADPH in the stimulated microsomal system, the hydrogen peroxide produced being broken down by a catalase activity in the microsomes. 5. Diquat can stimulate NADH oxidase and NADPH oxidase activity in the postmicrosomal soluble fraction; the enzyme involved may be DT-diaphorase. 6. The mechanism of these reactions and their significance in relation to the toxicity of the dipyridilium compounds are discussed.
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- CLARK J. B., GREENBAUM A. L., SLATER T. F. EFFECTS OF TETRAZOLIUM SALTS ON OXIDATIVE PHOSPHORYLATION IN RAT-LIVER MITOCHONDRIA. Biochem J. 1965 Mar;94:651–654. doi: 10.1042/bj0940651. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Clark D. G., McElligott T. F., Hurst E. W. The toxicity of paraquat. Br J Ind Med. 1966 Apr;23(2):126–132. doi: 10.1136/oem.23.2.126. [DOI] [PMC free article] [PubMed] [Google Scholar]
- DAVENPORT H. E. PATHWAY OF REDUCTION OF METMYOGLOBIN AND NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE BY ILLUMINATED CHLOROPLASTS. Nature. 1963 Jul 13;199:151–153. doi: 10.1038/199151a0. [DOI] [PubMed] [Google Scholar]
- ERNSTER L., DANIELSON L., LJUNGGREN M. DT diaphorase. I. Purification from the soluble fraction of rat-liver cytoplasm, and properties. Biochim Biophys Acta. 1962 Apr 9;58:171–188. doi: 10.1016/0006-3002(62)90997-6. [DOI] [PubMed] [Google Scholar]
- GILLETTE J. R., BRODIE B. B., LA DU B. N. The oxidation of drugs by liver microsomes: on the role of TPNH and oxygen. J Pharmacol Exp Ther. 1957 Apr;119(4):532–540. [PubMed] [Google Scholar]
- WILLIAMS C. H., Jr, KAMIN H. Microsomal triphosphopyridine nucleotide-cytochrome c reductase of liver. J Biol Chem. 1962 Feb;237:587–595. [PubMed] [Google Scholar]
- Zweig G., Shavit N., Avron M. Diquat (I,I'-ethylene-2,2'-dipyridylium dibromide) in photo-reactions of isolated chloroplasts. Biochim Biophys Acta. 1965 Nov 29;109(2):332–346. [PubMed] [Google Scholar]