EK - allosteric regulation

[Monkeymaniac]

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EK talks about how allosteric regulation involves allosteric inhibitor/activator changing the conformation of the enzyme.

Feedback inhibitors do not resemble the substrates of the enzymes that they inhibit. Instead, they bind to the enzyme and cause a conformational change. This is called allosteric regulation.

But then one of the in-class question says something otherwise.

Q. One mechanism of enzyme inhibition is to inhibit an enzyme without blocking the active site, but by altering the shape of the enzyme molecule. This mechanism is called:

A. competitive inhibition
B. noncompetitive inhibition
C. feedback inhibition
D. positive inhibition.

The answer is B. the explanation is that noncompetitive inhibition changes the configuration of the enzyme.

Isn't feedback inhibition (or negative feedback) and positive feedback types of allosteric regulations? Can C also be the answer, or is it the case that allosteric regulation doesn't always change the conformation of the enzyme?

 

[Fifty 3rds]

Feedback inhibitors can do plenty of things, not the least of which is allosterically inhibit an enzyme, but I don't believe that is their only modus operandi. They can affect enzymes multiple ways.

The most direct answer to the question you posted is B. Because a non-competitive inhibitor does not bind the active site.

 

[illegallysmooth]

Allosteric regulation that lessens the action of the enzyme is a form of non-competitive inhibition.

 

[Monkeymaniac]

Holy ****, I'm thoroughly confused.

1) I think allosteric regulation means regulating enzyme activity by effectors (activators/inhibitors) binding at non-active sites (allosteric sites). Does this mean allosteric regulation include both non-competitive inhibitors and feedback inhibitors?

2) Doing a quick search on wiki http://en.wikipedia.org/wiki/Allosteric_regulation shows that allosteric inhibitino decreases the affinity for substrates at active sites. But then, non-competitive inhibitor doesn't change the km, which is the measure of enzyme-substrate affinity. But then the definition of the allosteric inhibitor above identifies NC inhibitor as an allosteric inhibitor. So what exactly is allosteric inhibitor then? Thanks in advance.

 

[loveoforganic]

1) Yes.

2) Km isn't a true measure of binding affinity, but honestly, I forgot all my kinetics crap so I can't illustrate what it really is. The distinction is a little involved.

 

[Don Draper]

Holy ****, I'm thoroughly confused.

2) Doing a quick search on wiki http://en.wikipedia.org/wiki/Allosteric_regulation shows that allosteric inhibitino decreases the affinity for substrates at active sites. But then, non-competitive inhibitor doesn't change the km, which is the measure of enzyme-substrate affinity. But then the definition of the allosteric inhibitor above identifies NC inhibitor as an allosteric inhibitor. So what exactly is allosteric inhibitor then? Thanks in advance.

This is beyond MCAT knowledge.

2. Michaelis constant = (K-1 + K2)/K1;

what it is? simply the affinity of an enzyme for a specific substrate. This occurs at substrate concentration equal to 1/2 Vmax.

Noncompetitive inhibitors do NOT interfere with binding of substrate to enzyme (hence Km unchanged), but they do lower the enzymes max velocity or Vmax. (this is where your confusion is)

 

[UCB05]

EK talks about how allosteric regulation involves allosteric inhibitor/activator changing the conformation of the enzyme.



But then one of the in-class question says something otherwise.

Q. One mechanism of enzyme inhibition is to inhibit an enzyme without blocking the active site, but by altering the shape of the enzyme molecule. This mechanism is called:

A. competitive inhibition
B. noncompetitive inhibition
C. feedback inhibition
D. positive inhibition.

The answer is B. the explanation is that noncompetitive inhibition changes the configuration of the enzyme.

Isn't feedback inhibition (or negative feedback) and positive feedback types of allosteric regulations? Can C also be the answer, or is it the case that allosteric regulation doesn't always change the conformation of the enzyme?

Don't confuse your terminology. Feedback inhibition is the process in which downstream products inhibit upstream enzyme activity. Noncompetitive inhibition is the mechanism by which this is achieved. What's more, feedback inhibition cannot be the answer if the question does not mention the source of the allosteric regulator.

 

[loveoforganic]

^Very good explanation.

 

[Silverfalcon]

Just see that B as a clear answer. C is a "maybe" answer because one user said, feedback inhibition can mean a lot of things (as in not just allosteric inhibition as the problem specifies).

 

[Longshanks]

EK talks about how allosteric regulation involves allosteric inhibitor/activator changing the conformation of the enzyme.



But then one of the in-class question says something otherwise.

Q. One mechanism of enzyme inhibition is to inhibit an enzyme without blocking the active site, but by altering the shape of the enzyme molecule. This mechanism is called:

A. competitive inhibition
B. noncompetitive inhibition
C. feedback inhibition
D. positive inhibition.

The answer is B. the explanation is that noncompetitive inhibition changes the configuration of the enzyme.

Isn't feedback inhibition (or negative feedback) and positive feedback types of allosteric regulations? Can C also be the answer, or is it the case that allosteric regulation doesn't always change the conformation of the enzyme?

If you are not affecting the binding site, and thus not COMPETING for the binding site it is noncompetitive inhibition. Allosteric inhibition is a form of noncompetitive inhibition.

For this problem:
D makes no sense - eliminate it
Obviously not A - eliminate it
C is very tempting if you're going through the problem quickly, however there are many types of feedback inhibition. This question is asking for what type of inhibition is being described, so by selecting C you are just rewording the question. Thus the correct answer is B, as the inhibitor is noncompetitively inhibiting the enzyme through allosteric inhibition.


As a side note: allosteric interactions can have positive consequences such as the increased affinity of Hb for O2 as heme domains bind O2. In this problem however, the allosteric interaction is inducing an inhibitory effect and thus noncompetitive inhibition.

 

[Stingarov]

Ahem. This is very relevant. Noncompetitors don't compete for the same binding site. Allo means "other", so think of it that way. It induces a conformational change by binding to an other site. Noncompetitive feedback inhib. can occur if the end product binds to the allosteric site. In other words, it can be noncompetitive AND feedback inhibition, if specified in the example that the end product does bind to the enzyme.