scholarly journals Evidence that the inhibition sites of the neurotoxic amine 1-methyl-4-phenylpyridinium (MPP+) and of the respiratory chain inhibitor piericidin A are the same

1991 ◽  
Vol 273 (2) ◽  
pp. 481-484 ◽  
Author(s):  
R R Ramsay ◽  
M J Krueger ◽  
S K Youngster ◽  
T P Singer

1-Methyl-4-phenylpyridinium (MPP+), the neurotoxic bioactivation product of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), interrupts mitochondrial electron transfer at the NADH dehydrogenase-ubiquinone junction, as do the respiratory chain inhibitors rotenone, piericidin A and barbiturates. Proof that these classical respiratory chain inhibitors and MPP+ react at the same site in the complex NADH dehydrogenase molecule has been difficult to obtain because none of these compounds bind covalently to the target. The 4′-alkyl derivatives of MPP+ inhibit NADH oxidation in submitochondrial particles at much lower concentrations than does MPP+ itself, but still dissociate on washing the membrane preparations, with consequent re-activation of the enzyme. The MPP+ analogues with short alkyl chains prevent the binding of 14C-labelled piericidin A to the membrane and thus must act at the same site, but analogues with alkyl chains longer than heptyl do not prevent binding of [14C]piericidin.

1971 ◽  
Vol 124 (1) ◽  
pp. 171-187 ◽  
Author(s):  
C. I. Ragan ◽  
P. B. Garland

1. A spectroscopic resolution has been made of the components contributing to the ‘iron-flavoprotein’ trough extending from 450 to 520nm in the reduced-minus-oxidized difference spectrum of submitochondrial particles of Torulopsis utilis. 2. Seven components were identified other than cytochrome b, ubiquinone and succinate dehydrogenase. On the basis of the effects of iron- and sulphate-limited growth of cells on their subsequently derived electron-transport particles, and also by consideration of analytical measurements of the concentration of FMN, FAD, non-haem iron and acid-labile sulphide in the electron-transport particles in relation to the magnitude of the spectroscopic changes, it was possible to identify five of these components as follows: species 1a, the flavin of NADH dehydrogenase ferroflavoprotein; species 1b, the iron–sulphur component of NADH dehydrogenase ferroflavoprotein; species 1′, the flavin of an NADPH dehydrogenase; species 2, an iron–sulphur or ferroflavoprotein component; species 3, the flavin of l-3-glycerophosphate dehydrogenase. Two additional components were a fluorescent flavoprotein, probably lipoamide dehydrogenase, and a b-type cytochrome reducible by NADH or NADPH but not reoxidizable by the respiratory chain. 3. Species 1b and 2 were undetectable in electron-transport particles from iron- or sulphate-limited cells, but could be recovered in vivo under non-growing conditions. 4. The recovery in vivo of species 2 but not species 1b was inhibited by cycloheximide. 5. The recovery of species 1b correlates with the recovery of site 1 conservation. 6. The recovery of species 1b with species 2 correlates with the recovery of piericidin A sensitivity. 7. Evidence is presented for an NADPH dehydrogenase distinct from NADH dehydrogenase. The oxidation of NADH and NADPH by the respiratory chain is sensitive to piericidin A, and an iron–sulphur protein common to both pathways (species 2) is suggested as the piericidin A-sensitive component. 8. The approximate E′0 (pH7.0) values of species 1 (a and b, low potential) and species 2 (high potential) indicate that site 1 energy conservation occurs between the levels of species 1 (a and b) and species 2.


Author(s):  
G. N. Novodarova ◽  
L. L. Kiseleva ◽  
M. Yu. Tuvin ◽  
A. I. Stetsenko ◽  
L. P. Sharova ◽  
...  

1984 ◽  
Vol 49 (1) ◽  
pp. 313-319 ◽  
Author(s):  
Věra Přikrylová ◽  
Petr Sedmera ◽  
Josef V. Jizba ◽  
Jindřich Vokoun ◽  
Helena Lipavská ◽  
...  

Reaction of daunomycinone (I) with alcohols and p-toluenesulfonic acid produces a mixture (~3 : 1) of its (7S)- and (7R)-O-alkyl derivatives II-IX. According to the 1H NMR evidence, the alicyclic ring exists in the 9H8 conformation in (7R)-O-alkyl derivatives, on the contrary to (7S)-epimers and 7-epi-daunomycinone that adopt the 8H9 conformation.


Author(s):  
D.M. Beltukova ◽  
V.P. Belik ◽  
Y.N. Antonenko ◽  
A.A. Bogdanov ◽  
G.A. Korshunova ◽  
...  

Author(s):  
Iago A. Modenez ◽  
Lucyano J.A. Macedo ◽  
Antonio F.A.A. Melo ◽  
Andressa R. Pereira ◽  
Osvaldo N. Oliveira Jr ◽  
...  

1990 ◽  
Vol 9 (1) ◽  
pp. 260-265 ◽  
Author(s):  
Rocco A. Paciello ◽  
Juan M. Manriquez ◽  
John E. Bercaw

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