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I know cyanide inhibits complex IV in the electron transport chain, but I don't understand why this makes it so toxic. If cyanide is bound to the complex, can't the electrons just bypass it and reduce oxygen directly? That way fewer protons would be pumped out of the matrix, but most still would, and aerobic respiration would just be less efficient, rather than stopping entirely.

Essentially what I'm asking is what causes the electrons to get "stuck"?

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    $\begingroup$ Electrons get stuck because they can't be passed to complex IV, and this causes a backup in all the complexes of the electron transport chain. Therefore the cell faces an energy crisis, and eventually causes death. $\endgroup$
    – user560
    Commented Dec 14, 2013 at 4:13
  • $\begingroup$ But that doesn't explain why the electrons have to be passed to complex IV. My question is why can't they bypass that complex if it's deactivated and just go straight to oxygen? From what I understand, premature electron leakage toward oxygen is one of the reasons cells don't produce ATP at the theoretical maximum efficiency. $\endgroup$
    – Tyler
    Commented Dec 14, 2013 at 4:22
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    $\begingroup$ That leakage is due to the inefficiency of the complex-specificity, i.e. sometimes the highly specific requirement of substrate for these electron-transfer enzymes relaxes and it allows some electrons to leak, forming free ionic oxygen radicals. Otherwise, they are very specific in what they reduce and hence cannot bypass the predetermined chain disabling the effect of cyanide. $\endgroup$
    – stochastic13
    Commented Dec 14, 2013 at 9:15
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    $\begingroup$ all these comments could be incorporated into answers - please don't answer questions in comments! $\endgroup$
    – MattDMo
    Commented Dec 14, 2013 at 14:32

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Cyanide binds cytochrome oxidase so as to prevent the binding of oxygen. Electron transport is reduced to zero, and none of the oxygen breathed in can be used. Cytochrome oxidase is one of a superfamily of proteins which act as the terminal enzymes of respiratory chains, so if the cyanide is binding to the cytochrome then it inhibits the process and making it dangerous. Another example I would give rotenone which binds competitively.

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    $\begingroup$ That makes sense; I think for some reason the mental model I was using involved oxygen just floating around the complexes and magically abducting electrons when they got close enough to one of them, but your answer combined with Satwik Pasani's fixed the blight of stupidity I seemed to be suffering from for a while there. Thanks. $\endgroup$
    – Tyler
    Commented Dec 15, 2013 at 2:53
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    $\begingroup$ This answer seems to suggest that rotenone inhibits cytochrome oxidase, but it doesn't, it inhibits electron transport at complex I > ubiquinone. $\endgroup$
    – Alan Boyd
    Commented Dec 15, 2013 at 11:21

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