Competitive Inhibitors
The competitive inhibitors had come, and they had come to steal the enzymes. Not long after their arrival, the enzymes had gotten themselves preoccupied in new relationships with those hot new inhibitors:
This meant that now, fewer enzyme-substrate complexes were forming, and even fewer products were forming. This was a sad day for all.
At the Relationships Institute of EnzymeLand, they began conducting some research to find out which competitive inhibitors were most successful at competing with substrates for enzymes. Once again, they came up with a shiny new equation, this time for the dissociation of the enzyme-inhibitor complex:
EI -> E + I
They gave this equation a rate constant of KI. Since this is the rate constant for the dissociation of EI to form free E and I, the lower the KI, the better the inhibitor was at competing with the substrate and hanging on to those relationships with the enzymes.
Another curious phenomenon that those Relationships Institute researchers found was that, if the substrate concentration was much higher than the inhibitor concentration, the substrates could easily outcompete the inhibitors and hence the Vmax returned to normal. Strength in numbers, as they say!
Of course, those nerds at the Relationship Institute wouldn't be nerds if they didn't like graphs. Here's the graph that they prepared earlier:
The y-intercept, which from my previous post was 1/Vmax, was the same regardless of whether the competitive inhibitor was present or not. The x-intercept (-1/Km), however, did change. This shouldn't be surprising, as those pesky inhibitors were preventing those enzymes and substrates from getting together for a while. Anyway, from the graph, 1/Km decreased, which incidentally meant that Km increased. (You do have to play around with opposites a bit when reciprocals are involved.)
Uncompetitive Inhibitors
The next lot of inhibitors decided that they would not be quite as selfish when they sought out the enzymes. Instead of taking the enzymes for themselves, they thought that they'd be polite and slot themselves in to the enzyme-substrate complex, like so:
(See? I told you that there'd be steamy bed action!)
Anyway, the result of this was that the enzymes and substrates could get together, but there'd always be an inhibitor waiting to join in the action. This decreased the substrates' morale, and prevented their transformation into a product. Strength in numbers didn't seem to overcome this problem either: no matter how much more substrate there was, as soon as that substrate got together with an enzyme, the inhibitor would be there too. Watching. Waiting.
What did the Relationships Institute think? Well, they started off with an equation again:
EIS -> ES + I
This time, they called the rate constant KIS. Once again, the lower the KIS, the more effective the inhibitor at preventing the formation of product.
Here's the graph that they made:
As you can see, the 1/Vmax increased, and so did 1/Km, which means that Vmax and Km both decreased. (Remember, reciprocals = opposite day). The Vmax decreased because as I said earlier, no matter how much substrate there was, an inhibitor would always be there to prevent its final transformation into a product. The change in Km is a bit less intuitive to understand though. You see, when the enzyme-substrate-inhibitor complex forms, that means that there is less ES floating around. That shifts the E + S <--> ES equilibrium in favour of ES formation. This means that eventually pretty much all the substrate you put in is going to end up as ES or EIS, so that the apparent Km ends up being lower than what you'd get without an uncompetitive inhibitor.
Noncompetitive (Mixed) Inhibitors
Noncompetitive (mixed) inhibitors decided that they'd be extra fancy and use both tricks: they'd steal free enzyme, just like the competitive inhibitors, and they'd insert themselves into an existing enzyme-substrate relationship, just like the uncompetitive inhibitors.
The characteristics of mixed inhibitors essentially combined the characteristics of competitive and uncompetitive inhibitors. The final outcome depended on how much competitive vs. uncompetitive inhibition that the noncompetitive inhibitor liked to engage in. If it was better at using competitive inhibition (i.e. KI < KIS - remember that a lower KI or KIS = better inhibition), then its characteristics would be closer to that of competitive inhibition, or vice versa.
No matter what kind of inhibition prevailed, noncompetitive inhibitors would always result in a lower Vmax. This is because competitive inhibition didn't have any effect on Vmax, while uncompetitive inhibition caused it to decrease.
Km got a bit more interesting, however. Noncompetitive inhibitors more adept at using competitive inhibition (i.e. KI < KIS) had a higher Km. The opposite was true for those more adept at uncompetitive inhibition: they had a lower Km. There were, however, some special noncompetitive inhibitors that were equally adept at using both: they didn't have any effect on the Km.
Irreversible Inhibitors
Many inhibitors were reversible, which meant that they, too, could suffer break-ups with enzymes. But there were a few that could not. These were the irreversible inhibitors.
They, masters of black magic, could bind irreversibly to the enzymes. Thus ended the romantic lives of those poor enzymes: no substrate would ever want to be with them now that they would have to put up with an inhibitor too. As time passed, more enzymes would be bound to inhibitors, and so their romantic activity would decrease.
Allosteric Enzymes
Forget the inhibitors- sometimes enzymes could be their own worst enemies. Enzymes could exist in either a tense state (T state) or a relaxed state (R state). When tense, their romantic lives suffered, and they couldn't form enzyme-substrate complexes quite so readily. They were much better partners in their relaxed state, however.
Most enzymes existed in an equilibrium between being tense and relaxed, which could be represented as T <--> R. Without substrate available, the tense state would prevail- I suppose because the enzymes were worried that they'd die lonely. Once some substrate came along and bound to that small percentage in the R state, however, the equilibrium would begin to shift. The enzymes would increase their morale as they saw their friends finding partners and settling down. As more substrate arrived, the more relaxed the enzymes became.
There were, however, other influences on whether enzymes were tense or relaxed. Allosteric inhibitors tended to make enzymes more tense, so that fewer enzyme-substrate complexes would occur. Allosteric activators, however, were the opposite: they would relax the enzymes so that they could find love more quickly.
And thus concludes this, er... lovely series of blog posts! Until next time!
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