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Specific inhibition by macrocyclic polyethers of mitochondrial electron transport at site I

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Abstract

The macrocyclic polyethers dibenzo-18-crown-6 (XXVIII) and dicyclohexyl-18-crown-6 (XXXI) inhibit the valinomycin-mediated K+ accumulation energized by glutamate, α-ketoglutarate, malate plus pyruvate or isocitrate but not that promoted by succinate, ascorbate plus TMPD or ATP. The polyethers inhibit the oxidation of the former group of substrates without preventing either the oxidation of succinate or ascorbate plus TMPD or the hydrolysis of ATP.

The substrate oxidation inhibited by the macrocyclic polyethers is relieved in intact mitochondria by increasing the concentration of K+ in the medium. It is also completely reverted by supplementing the medium with valinomycin, Cs+ and phosphate, or else by the addition of vitamin K3.

In submitochondrial sonic particles the macrocyclic polyethers inhibit the oxidation of NADH as well as the ATP-driven reversal of electron flow at the site I of the electron transport chain. They also block the oxidation of NADH in non-phosphorylating Keilin-Hartree particles as well as in Hatefi's NADH-coenzyme Q reductase. The polyethers do not inhibit electron transport in mitochondria from the yeast which lack the first coupling site.

The inhibition of electron transport by the polyethers do not require of the addition of alkali metal cations such as K+ in intact mitochondria or other membrane preparations.

It is established that the macrocyclic polyethers XXVIII and XXXI, already characterized as mobile carrier molecules for K+ in model lipid membranes, inhibit electron transport at site I of the electron transport chain from mitochondrial membranes.

It is suggested that the ability of the polyethers to coordinate alkali metal cations in aqueous versus lipid environments, but not K+ transportper se, is related to their rotenone-like induced inhibition of electron flow in mitochondrial membranes.

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Author notes

  1. Alfonso Cárabez

    Present address: Departamento de Bioquimica Facultad de Medicina, Ciudad Universitaria, México 20, D. F.

Authors and Affiliations

  1. Department of Biochemistry Centro de Investigación y Estudios Avanzados del, Instituto Politécnico Nacional, P.O. Box 14-740, México 14, D. F., Mexico

    Sergio Estrada-O & Alfonso Cárabez

Authors
  1. Sergio Estrada-O
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  2. Alfonso Cárabez
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Supported in part by a Grant from the Research Corporation.

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Estrada-O, S., Cárabez, A. Specific inhibition by macrocyclic polyethers of mitochondrial electron transport at site I. J Bioenerg Biomembr 3, 429–443 (1972). https://doi.org/10.1007/BF01516081

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  • DOI: https://doi.org/10.1007/BF01516081

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