Reduction of nifurtimox and nitrofurantoin to free radical metabolites by rat liver mitochondria. Evidence of an outer membrane-located nitroreductase.

作者: S N Moreno , R P Mason , R Docampo

DOI: 10.1016/S0021-9258(20)82140-1

关键词: NitroreductaseEnzymeNifurtimoxNAD+ kinaseSuperoxideBiochemistryChemistryBacterial outer membraneMitochondrionRespiratory chain

摘要: Nifurtimox and nitrofurantoin are reduced by intact rat liver mitochondria to nitro anion radicals whose autoxidation generates superoxide as detected direct electron spin resonance spectroscopy spin-trapping experiments, respectively. Although nitroreduction occurred in the presence of respiratory substrates such beta-hydroxybutyrate, malate-glutamate, succinate, or endogenous substrates, radical formation activity was much greater on addition exogenous pyridine nucleotides. NAD(P)H generated from mitochondrial NAD(P)+ intramitochondrial reactions could not be used for nitroreductase unless were solubilized detergent. In addition, crude outer membrane fraction, with a higher than mitoplasts mitochondria. These results provide evidence nitrofuran reductase associated that is far more important chain enzymes.

参考文章(51)
Albert L. Lehninger, Phosphorylation coupled to oxidation of dihydrodiphosphopyridine nucleotide. Journal of Biological Chemistry. ,vol. 190, pp. 345- 359 ,(1951) , 10.1016/S0021-9258(18)56077-4
H.R. Mahler, Isaias Raw, Rubens Molinari, Dea Ferreira do Amaral, Studies of electron transport enzymes. II. Isolation and some properties of a cytochrome-specific reduced diphosphopyridine nucleotide dehydrogenase from pig liver. Journal of Biological Chemistry. ,vol. 233, pp. 230- 239 ,(1958) , 10.1016/S0021-9258(19)68062-2
Gian Luigi Sottocasa, Bo Kuylenstierna, Lars Ernster, Anders Bergstrand, [72c] Separation and some enzymatic properties of the inner and outer membranes of rat liver mitochondria Methods in Enzymology. ,vol. 10, pp. 448- 463 ,(1967) , 10.1016/0076-6879(67)10077-3
C. de Duve, B. C. Pressman, R. Gianetto, R. Wattiaux, F. Appelmans, Tissue fractionation studies. 6. Intracellular distribution patterns of enzymes in rat-liver tissue* Biochemical Journal. ,vol. 60, pp. 604- 617 ,(1955) , 10.1042/BJ0600604
M C Beatrice, D L Stiers, D R Pfeiffer, The role of glutathione in the retention of Ca2+ by liver mitochondria. Journal of Biological Chemistry. ,vol. 259, pp. 1279- 1287 ,(1984) , 10.1016/S0021-9258(17)43600-3
R. Docampo, R.P. Mason, C. Mottley, R.P. Muniz, Generation of free radicals induced by nifurtimox in mammalian tissues. Journal of Biological Chemistry. ,vol. 256, pp. 10930- 10933 ,(1981) , 10.1016/S0021-9258(19)68534-0