Types of Inhibition - Biochemistry

To answer this question, we need to understand what competitive inhibition is. When a competitive inhibitor is present, an enzyme's active site will be able to bind either substrate or the inhibitor. Thus, for a given substrate concentration, the reaction will be slower in the presence of the inhibitor because sometimes the inhibitor will interfere with the binding of the substrate to the enzyme's active site. However, we're not looking for reaction rate at a given substrate concentration. Instead, we are looking at the maximum possible reaction rate given any amount of substrate concentration. If we keep adding more and more substrate in the presence of the inhibitor, eventually we will get to a point where there is so much substrate present that having the inhibitor around doesn't make a difference on the reaction rate. Therefore, the addition of a competitive inhibitor has no effect on the of an enzyme catalyzed reaction.

Competitive inhibitors bind the active site of enzymes, and compete with the substrate for this binding site. Thus, the does not change since if enough substrate is added, regardless of the differential affinities between the substrate and inhibitor for the active site, the substrate will outcompete the inhibitor. However, increases upon the addition of a competitive inhibitor.

Competitive inhibition is characterized by an increase in the Michaelis-Menten constant, . Note that this constant represents the substrate concentration at which half the enzymes are occupied with substrate. If increases, then it suggests that a higher concentration of substrate is needed to occupy half the enzymes. is also a measure of the affinity between substrate and enzyme. As increases, the affinity decreases and more substrate is required to bind 50% of the enzyme. Competitive inhibitors bind to the active site of the enzyme and compete with the substrate for the binding site on the enzyme, thereby decreasing the affinity and increasing .

Competitive inhibitors do not alter the maximum velocity of an enzyme-substrate reaction. Recall that enzymes speed up reactions; therefore, the velocity of a reaction is a direct measure of its efficacy. This means that competitive inhibitors do not alter the efficacy of the enzyme.

Competitive inhibitors bind to the active site of the enzyme and prevent substrates from binding to enzyme. This prevents the enzyme-substrate reaction from happening, thereby decreasing the activity of enzymes; however, competitive inhibitors can be overcome by increasing the concentration of substrates. Increase in the amount of substrates will displace the inhibitors from the active site and allow for substrates to bind. This will bring the efficacy of the enzyme back up to normal levels.

Increasing and decreasing the volume of the solution will concentrate or dilute all species in the solution, respectively. This will not decrease the effects of competitive inhibitors on the enzyme.

There are two types of sites on the enzyme where molecules can bind. Active sites are the main location for substrate-enzyme binding. These sites usually involve weak, reversible bonds (such as hydrogen bonds) between substrate and enzyme. Allosteric site, on the other hand, are found at a different location on the enzyme and bind certain types of inhibitors and modulators of the enzyme. These are usually more permanent bonds (covalent bonds) and are irreversible.

Competitive inhibitors bind to active sites and form weak, reversible bonds. This is why we can dissociate competitive inhibitors from the active site by increasing the concentration of substrates. Substrates will compete for the active site and displace bound competitive inhibitors.

Competitive inhibitors bind to the substrate binding site of an enzyme and have the following effect: Increase , No change in .

Noncompetitive inhibitors bind to a site other than the substrate binding site and have the following effect: No change in , Decrease in .

Increasing the , lowers the affinity since the is the substrate concentration at which the reaction proceeds as one-half of .

Because carbon monoxide binds at the same site as oxygen, this is a form of competitive inhibition. In order to overcome this type of inhibition, the concentration of substrate (oxygen) needs to be increased.

The type of inhibition being described here is competitive. The carbon monoxide binds to the same site that oxygen does. Therefore, by increasing the amount of substrate available, the inhibitor can be outcompeted. This is why Vmax for competitive inhibition is unchanged. Km on the other hand, is decreased for competitive inhibition.

A molecule can only competitively inhibit another molecule if it fits into the same active site in the enzyme. In the reaction, goes into the active site of the enzyme, and so only a molecule with its similar structure can competitively inhibit it - .

Competitive inhibitors bind to the active site of the target enzyme. Km is the substrate concentration at which the reaction rate is at half Vmax. A competitive inhibitor can be outcompeted by adding additional substrate; thus Vmax is unaffected, since it can be accomplished with enough additional substrate. However, since we need to add additional substrate to compete with the inhibitor to get the reaction to the same rate, our Km increases.

This is an example of feedback inhibition, as feedback inhibition is a mechanism in which a molecule binds to an enzyme to decrease its activity. The mechanism is now balanced. Blocking an enzyme typically helps correct a metabolic imbalanace or assists in destruction of a pathogen. In this case the ATP binds to a site other than the protein's active site, and since it blocks PFK-1, a feedback inhibition has occurred.

The graph shown in the question stem is a Lineweaver-Burk plot, otherwise known as a double-reciprocal plot. In this plot, is plotted along the -axis and is plotted along the -axis. Furthermore, the -intercept in such a graph is equal to , and the -intercept is equal to .

From the graph shown in the question stem, we can see that there are two lines, each with different slopes. Each line corresponds to a certain concentration of inhibitor. (Note that one of the lines corresponds to no inhibitor, or a concentration of 0.)

It is evident that the two lines intersect each other along the -axis, right on the value. Consequently, we can conclude that the inhibitor in this case is not having any effect on the value of for the enzyme. Despite the different slopes for the two reactions, both of them have a common -intercept but differing -intercepts. This means that we can conclude the inhibitor in question must be competitive, since the result will be a rise in the value for the enzyme-catalyzed reaction, but will have no effect on the value.

This scenario is a classic example of allosteric inhibition. When cyanide binds to a site on cytochrome c oxidase other than the active site, cytochrome C oxidase becomes deactivated, stopping oxidative phosphorylation and causing cells to die since they cannot produce ATP anymore.

In competitive inhibition, the inhibitor binds the active site of the enzyme, competing with the substrate for this binding site. The of a competitively inhibited enzyme remains unchanged, but the increases. This means that a higher concentration of substrate is required to bring the reaction rate to . However, since this is competitive inhibition, and the maximum velocity is unchanged, we can overcome this increase in and achieve maximum velocity if we saturate the enzyme with substrate.

All types of inhibitors will induce a change in the of an enzyme except for competitive inhibitors. This is because competitive inhibitors have no effect on the enzyme-subtrate complex. The may still be reached, but by adding more substrate, since the is increased by a competitive inhibitor.

Competitive inhibition involves the substrate's access to the active site. In the case of competitive inhibition, the inhibitor blocks the substrate from the active site. As a result, the is unchanged, but the is increased. Recall that is the substrate concentration at which the reaction rate is . Additionally, the reaction rate will increase with increased concentration of competitive inhibitor and substrate, because they are competing for the active site, causing an increase in reaction rate.

Uncompetitive inhibitors can only bind the ES complex, whereas competitive and non-competitive inhibitors do not require the enzyme to be complexed with the substrate. , which describes the maximum reaction velocity of the enzyme, is decreased because the inhibitor slows the dissociation of the substrate from the enzyme, thereby slowing the rate at which the enzyme can interact with other substrate molecules.

This question is presenting us with a situation in which a chemical is being added to a mixture of enzyme and substrate, and its effects on the kinetic parameters of the reaction are observed. We're told that the and for this reaction both become reduced. We then are asked to identify which term best describes the added chemical.

To begin with, let's take note that all of the answer choices are some kind of inhibitor. Thus, we know that the chemical we're adding to the mixture is an inhibitor of some type. The challenge is in identifying which type of inhibition is happening. For this question, we'll need to have familiarity with each type of inhibition in order to identify the correct answer.

Let's start with what we know. Both the and the are being decreased. Right away, we can rule out competitive inhibition because the should remain the same.

We should also be able to rule out feedback inhibition right off the bat, as this kind of inhibition involves the products of a reaction putting a halt on the reaction that led to its production.

Next, we can also realize that two of the answer choices are so similar that they are actually saying nearly the same thing. Mixed inhibition is a case in which the inhibitor binds to the enzyme regardless of whether substrate is also bound to the enzyme. However, with mixed inhibition, the inhibitor shows greater affinity for either the free enzyme or the enzyme-substrate complex. In such a case, the for the reaction is expected to fall, but the can either increase or decrease.

Noncompetitive inhibition is a special type of mixed inhibition, in which the inhibitor binds both the free enzyme and the enzyme-substrate complex with equal affinity. In such a situation, the of the reaction will fall, but the will remain unchanged.

And finally, we look at uncompetitive inhibition, which is the correct answer. In this type of inhibition, the inhibitor binds only to the enzyme-substrate complex rather than the free enzyme. It does so by binding to an allosteric site, which is distinct from the active site to which substrate binds. Thus, there is no way to out-compete the inhibitor by adding more and more substrate, as can be done in competitive inhibition. The end result of this is that the becomes irrecoverably lowered. And since this value becomes less, the substrate concentration needed to obtain half of that reduced value (the ) also becomes decreased.

In feedback inhibition, the substances at the end of a reaction (in this case, CTP, the product) inhibit a previous reaction (in this case, the CTPase reaction). This tells the CTPase that a substantial amount of CTP is present, and to stop engaging in the reaction. The opposite, when a metabolic product facilitates further synthesis of that product, is known as positive feedback. Zymogens are inactive enzyme precursors - examples are pepsinogen and angiotensinogen. Cooperativity refers to the changes in binding affinity of an enzyme with multiple binding sites to its ligands. For example, hemoglobin has four oxygen binding domains; when one oxygen is bound, it facilitates the binding of the second, third, and fourth oxygens. Negative cooperativity is the opposite of this.