HCN, answer to an interesting question

For the record the pKa of HCN is about 9 which is considerably more acidic than ROH (pKa of 18).

This is from a very cool book we have in the library called,
Doull, J. ; Klaassen, C. D. , Amdur, M. O. "Casarett and Doull's Toxicology: The basic science of poisions" , second edition

I found something on the mechanism of action of HCN. I thought I would share it with the entire class because it involves oxidative phosphorylation, something we were recently talking about in class in the context of quinones and besides it is just plain fascinating.

The condition that results from HCN poisioning is called histotoxic hypoxia - this is technically an incorrect term because it implies that peripheral tissues do not receive an adequate supply of oxygen. I was thinking along this lines as I lay in bed last night stewing over how HCN might work - I thought of all those detective novels where the person has blue lips after cyanide poisioning and also the similiarity in structure to carbon monoxide that binds hemoglobin with a higher affinity than oxygen. I figured it was binding the hemoglobin and preventing the absorption of oxygen. Anyway, I was wrong. In cyanide poisioning the pressure of oxygen in the tissues is just fine. It is the ability of the tissues to utilize oxygen that is altered.

HCN interupts electron transport down the cyctochrome chain by inhibiting at the cytochrome a to cytochrome a3 step. This is a little closer to the vague explanation I gave in class when I said that some poisons act as inhibitors. What this means is that the enzyme complex I talked about in class ( cyctochrome reductase) which takes the electrons from the ubiquinol (converting ubiquinol back to ubiquinone) binds HCN at one of its binding sites. This essentially stops the enzyme from functioning so the electrons never get delivered to molecular oxygen to form water.

Because the oxygen pressure starts to build in the tissue, the ability of oxyhemoglobin to unload its oxygen is decreased and the concentration of oxyhemoglobin builds up. For this reason, people who have cyanide poisoning have a flushed appearance.

Some more interesting stuff...

One source that has been responsible for cyanide poisioning is amygdalin, a cyanogenic glycoside found in nature. This compound is the major ingredient in laetrile. When this anticancer agent is used, certain intestinal microflora apparently have the enzymes necessary to break the amygdalin down, releasing cyanide. People taking the controversial laetrile treatments have died from cyanide poisioning. I wonder if this mechanism has anything to do with the way it kills cancer cells. I think this demonstrates that just because something is "natural" does not mean it is safe. Remember everything is toxic in some dose.

Treatment of cyanide poisioning involves intravenous injection of sodium nitrite. This is just so neat - after this you will believe that medicine is CHEMISTRY.

The sodium nitrite converts hemoglobin into methomoglobin (I have to find the structure of this - but I know it is deoxygenated). The methemoglobin successfully competes with the cytochrome enzyme for the cyanide. Of course the cyanide binds the modified hemoglobin really well and this of course knocks a percentage hemoglobin out of commission. So what do you do next? You administer sodium thiosulfate intraveniously. This compound serves as a substrate for an enzyme called rhodanese - which detoxifies the cyanide by converting it into thiocyanate which is excreted in the urine.

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