Inhibition of Inhibition of Inhibition

There is much to cause fatigue in readers of biochemical communications, but for me the phrase "prevents the inhibition of" is the champ. Especially when the process being inhibited has as its known objective the production of an inhibitor of yet another process. While double negatives may be OK in many languages other than English and Turkish, and I am perfectly used to them in Portuguese (as I am used to run-on sentences in Slovene, or at least Slovene journalism), they still bug me in biochemistry. Is it really like that? Something is doing something, a second thing is trying to thwart it, and a third thing is trying to thwart the second thing?

At this point I ought to be challenged to give an example. But I'm too fatigued to comply. Still, I did get the idea that such a setup may not be so linear as the last italicized bit has it. That is, something is doing something only if two other substances are present in a certain ratio, and if they aren't - one or the other is too high or too low - you get either "inhibition" or "inhibition of inhibition of inhibition," which works out to the same thing. The process of interest is hindered at n removes, where n is an even number, and it's the ratio of the concentrations of inhibitor #0 to inhibitor #-2 (or inhibitor #-4, or inhibitor #-6, etc.) that matters.

So, the objective here is to set up a model where you can fiddle with such ratios, primarily of just [inhibitor #0] to [inhibitor #-2] though you can try the other combinations, and see if one narrow range gives a big spike or dip in throughput for a certain process. Certainly if the concentration of any such inhibitor is well above its relevant binding constant, there can't be anything tricky or surprising going on, but for values at or below, things might get gratifyingly hairy.

I was going to simplify this by arbitrarily fixing the concentration of almost every substance in play, which in turn would require fixing the rate constants of the processes that yielded and disposed of them, but that seemed like OVERsimplification. So, you get to set practically everything yourself. Rate constants may be taken as per-second, and concentrations and binding constants as micromolar, but it shouldn't matter because the output is unitless. As elsewhere on this subsite, some values have been hazarded and preset, but you can change 'em all. To facilitate keeping track of such changes, I've given this demo a lot of mouse power: you can highlight whatever it is you're changing or looking at, or thinking about changing or looking at, by hovering over variable names on either the left-hand, JavaScript side or the right-hand, Java side. The nomenclature is tricky, I'll freely allow. Further notations on the functionality are given here, here, here, and here. All Java applet stuff. I'm not real sanguine about the things, but as of the last "here," they run.

Also through that last link, you may find something useful or at least consoling if there's NOTHING working on the southeast quadrant of this page. See the 10/15/10 entry regarding applet performance in IE8 with Windows 7.

The reaction of immediate interest is:
A ------> B ------> something else

It is [B] that needs to be governed by some inhibitor, or some inhibitor ratio. You'll start by establishing which ratio, with the radio buttons to the right. What you're immediately doing is fixing the rate at which 1 of 3 inhibitors is degraded. The ratio of the other two rates is what will be varied.
A-to-B is inhibited competitively by I, with binding constant KIvsA. I itself is produced and degraded as follows:
preI --------> I --------> something else
preI-to-I is inhibited competitively by H, with binding constant KHvsI. H itself is produced and degraded as follows:
preH --------> H --------> something else
preH-to-H is inhibited competitively by G, with binding constant KGvsH. G itself is produced and degraded as follows:
preG --------> G --------> something else