November 12, 2019, 10:37:24 PM
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Topic: How metaldehyde is metabolised by the body  (Read 272 times)

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Offline Halsyeet

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How metaldehyde is metabolised by the body
« on: August 28, 2019, 10:09:33 AM »
I'm trying to complete an assignment regarding metaldehyde toxicity in dogs and it seems the exact mechanism of metaldehyde is unknown...

What I've managed to learn (hopefully correctly) is that it enters the body and is absorbed by the gastrointestinal tract and into the enterohepatic circulation. It is converted into acetaldehyde when it comes into contact with acid (stomach acid) and then this is where google has stumped me. I see some saying that the aceteldehyde is oxidised to acetic acid, and one saying it's rapidly oxidised to carbion dioxide... Hopefully someone can shed some light on this subject for me.

Thanks!

Offline Babcock_Hall

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Re: How metaldehyde is metabolised by the body
« Reply #1 on: August 28, 2019, 05:18:19 PM »
There is a great deal of information on acetaldehyde metabolism.  Have you studied the Krebs' cycle?

Offline Halsyeet

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Re: How metaldehyde is metabolised by the body
« Reply #2 on: August 28, 2019, 08:39:43 PM »
I haven't. I'm just a veterinary nursing student.  :-[

I've now learned that it's the aldehyde dehydrogenase enzymes that oxidise aceteldehyde to acetic acid. I'm having trouble figuring out what happens next, although apparently this acetic acid is the second main ingredient in vinegar.

Offline Babcock_Hall

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Re: How metaldehyde is metabolised by the body
« Reply #3 on: August 29, 2019, 10:06:35 AM »
Acetate (the conjugate base of acetic acid)* is converted into acetyl coenzyme A (acetyl CoA) by the enzyme acetyl CoA synthetase.  This can enter the Krebs' cycle (also known as the tricarboxylic acid cycle), be incorporated into fatty acids, or go into other pathways.  It is the reactions of the TCA cycle that make carbon dioxide from the carbon atoms within acetyl CoA. BTW acetaldehyde is also produced when one drinks ethanol.  Ethanol is converted into acetaldehyde by alcohol dehydrogenase.

For your own interest, you might want to look into how ethylene glycol is metabolized.  Veterinarians sometimes have to treat dogs who drink antifreeze, and oxidation of ethylene glycol produces oxalate, a very toxic compound.

*In the bloodstream for example (pH 7.4) acetate would be the main form.  What do you think might be the case if acetate were found in the stomach?

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