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Different types of superoxide dismutase (SOD) contain different metal ions (Zn, Cu, Mn, Ni, or Fe), all of which allow them to catalyze one reaction, dismutation of superoxide anion, O2−. Cyanide can block this reaction, but only in CuZnSOD.

What is the (bio)chemical mechanism behind cyanide inhibition of CuZnSOD and why doesn't it occur in FeSOD or MnSOD?

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  • $\begingroup$ It would be nice if you could add some references to your question. $\endgroup$
    – Alexander Galkin
    Mar 4, 2012 at 9:07

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I'm just taking a stab, because my inorganic chemistry is rusty.

cyanate (CN-) is well known to bind to iron (it inhibits hemoglobin and causes anoxia), and it also forms a pretty strong complex with Zinc:

http://en.wikipedia.org/wiki/Zinc_cyanide

I would guess that in the case of the SOD that the other liganding amino acids and the pocket of the enzyme are such that the affinity for cyanide is lowered to the point that oxygen can displace it.

In the case of hemoglobin, CN will coordinate to the heme iron in much the same fashion that O2 does, but it doesn't come off. In the case of SOD, the enzyme will be looking to coordinate to superoxide O2(2-) which would be at a roughly tetrahedral angle to the metal. This is not a favored geometry for CN coordination, which prefers to linearly coordinate to things.

In the case CuZnSOD it seems likely that this enzyme has enough room and its Zn and Cu binding envirionments don't forbid CN binding. it would be an evolutionary accident really as to why one is sensitive and another is not.

some structures at rcsb:

SODs: http://www.rcsb.org/pdb/results/results.do?qrid=C0740111&tabtoshow=Current

thiocyanate bound. the pocket is pretty open between the two ions. no CN bound structure. http://www.rcsb.org/pdb/explore/jmol.do?structureId=1SXS&bionumber=1

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One can argue that only the "eukaryotic" types of SOD are sensitive to cyanide treatment:

  1. FeSOD is designated as "prokaryotic" type of SOD which is uncommon (but possible) for eukaryotes (reference).
  2. CuZnSOD is a cytosolic SOD, whereas MnSOD is located within mitochondria (reference). Taking into account the endosymbiotic theory we might also suggest that MnSOD is also a sort of "prokaryotic" SOD.
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    $\begingroup$ This answer is not yet a biochemical mechanism. $\endgroup$
    – Thomas Ingalls
    Mar 4, 2012 at 9:57

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