"....maybe you can tell us if I neglected to consider what Richard brings up - he's claiming that there is only one unique binding point for an imidacloprid molecule, and that the breakdown thereof yields two or more molecules, but only one that can bind to a receptor, and one (or more) that cannot. Apparently, there's no way to tell which one ends up with the bit that does the binding, which runs counter to what I thought I knew about how enzymes do their jobs."
This conversation is fun! It is forcing me to recall stuff that has been lost in my brain for years.
OK. Dick's analogy about metabolism was helpful....car going down road, losing pieces at forks...but in terms of how biology works it needs amending.
Imagine that at each fork in the road, there is a "pit crew". They take off the windshield wipers, but add spoilers at the first fork. The next crew takes off the roof and turns the car into a convertible. Etc.
As molecules like imidacloprid are metabolized, they go through steps in which they are changed into something else that involves ADDING as well as subtracting atoms/molecules to the basic structure. Eventually, they are changed into something that can finally be eliminated using existing metabolic pathways. The end products of complete metabolism are CO2, water, and sometimes nitrogen (ammonia), depending on what is being broken down. However, engineered drugs are different because the body has not evolved to handle them well. This is why some drug testing in athletes involves investigating urine samples. Some of the metabolites are NOT broken down. Hopefully, they are excreted. Sometimes they are not.
I looked up the molecular weights and formulas of IMI and the two metabolites we've been discussing. I can't post the structural diagrams here but you can find them in Suchail's 2003 paper or online, just Google the chemical names below:
Imidacloprid: C9H10ClN5O2 molecular weight 256
5-hydroxyimidacloprid C9H10ClN5O3 molecular weight 272
Olefin....Suchail 2003 provides full name, it is 1-(6-chloro-3-pyridylmethyl)-N-nitro-4-imidazolin-2-ylideneamine (!!) Molecular weight is 255, chemical formula is C9H10ClN5O2
Notice they are all about the same size....as I mentioned, this is typical as the body tries to re-structure the compound to a form that it is able to break down.
All three of the above molecules retain the active binding site. Presumably, at some later iteration of re-structuring, that binding site will be deactivated. Unfortunately for the bee, it's not happening in the first steps, as we have learned.
When we study biochemistry we are given nice and tidy drawings of all metabolic steps in a given reaction, as anyone who has had to memorize the Krebs cycle knows all too well (and that includes me...UGH). However, in this case we can't make that drawing because we don't know what all the steps are. All we know is that two of the metabolites have binding affinity at least as good as the parent compound, and we know they persist longer in the bee than the parent compound does....that's why they are called "more toxic", because they persist longer and bind fiercely to the acetylcholine receptor.
Maybe somebody has figured out all the metabolic steps for imidacloprid in the bee. That's what I was trying to find out on Sunday, when I posted the summary of what I found for soil, plants, and mammals...but there's very little on insects. I did learn that one of the pest species has less sensitivity to the olefin and 5-hydroxy metabolites than the honeybee has, and also that bumblebees are more susceptible to IMI than honeybees are, but I can't find a complete metabolism profile for IMI in the honeybee (or any other insect). Anyone else have luck with that?
Christina
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