Negative Feedback: Videos & Practice Problems

Negative feedback, or feedback inhibition, is a crucial mechanism for regulating biochemical reactions in cells. It prevents overproduction and waste by allowing a final product to inhibit an earlier step in its metabolic pathway. This process involves an allosteric enzyme, where the product binds to an allosteric site, effectively slowing down the pathway and decreasing the product's concentration. Once levels normalize, inhibition ceases, allowing the pathway to resume. This efficient regulation is vital for maintaining homeostasis in cellular metabolism.

Negative Feedback

In this video, we're going to introduce yet another way that cells can regulate their biochemical reactions, and that is through negative feedback. And so negative feedback is also sometimes referred to as just feedback inhibition. And so negative feedback or feedback inhibition is an efficient and a very common means for biochemical regulation. And so cells use negative feedback all the time to regulate their reactions. Now really the purpose of negative feedback is to prevent the overproduction as well as the wasteful production of a product. And so as we'll see moving forward, negative feedback is really just a way for molecules such as a product to regulate the production of its own activity. And so negative feedback inhibition is when the final product or just a later product in a metabolic pathway can come back and inhibit an earlier step in the same exact metabolic pathway that led to that product's production. And so ultimately, this is going to slow down the entire metabolic pathway, and that is going to begin to decrease the final concentration of that product that acted to inhibit the reaction. And so, as we'll see down below in our example, negative feedback inhibitors really do, inhibitors, really do act as inhibitors. And recall that inhibitors are commonly represented with a negative symbol. And so these negative feedback inhibitors are going to bind to an allosteric an allosteric site on the allosteric enzyme and of course that means that it's not going to bind to the enzyme's active site. And so down below in our example, notice we're saying that negative feedback inhibition really acts like the red light, to inhibit metabolic pathways. And so over here what we have is a red light to show you that, really negative feedback acts like a red light and slows down these, metabolic pathways. And so over here we're showing you an example of a metabolic pathway. And so you can see that we have all of these reactions here and notice that most of these reactions are being catalyzed by Michaelis Menten enzymes. But here we do have one enzyme that is displaying allosteric kinetics. And so, notice here that we have a final product f and if the concentration of f happens to get way too high, then f can actually come back and inhibit the allosteric enzyme number 1 here. And we know that it's inhibiting because, again, we have a minus sign here, that represents inhibition. And so if f comes all the way back to inhibit enzyme number 1, then that's going to prevent the conversion from a to b. And, ultimately, that's going to lead to the decrease of the concentration of product f. And so when the final concentration of the product f over here is returned back to normal or lower levels, then, the feedback inhibition that is caused by product f here is essentially going to stop, and that's going to allow the metabolic pathway to proceed once again. And so, clearly here we're talking about negative feedback inhibition. And you can see how really through negative feedback inhibition, molecules such as product f here are able to regulate their own production. And so, by coming back and inhibiting enzyme number 1, product f can influence the decrease or the lowering of its concentration. And so, it turns out again that negative feedback inhibition is an efficient and a common means for biochemical regulation. So later in our course we're going to talk about many different examples of negative feedback. And in our next lesson video, we'll specifically talk about one particular example. And so, I'll see you guys in that video.

Negative Feedback Example 1

So now that we've covered the basics of negative feedback or feedback inhibition, in this video we're going to cover an example of feedback regulation in glycolysis. And so recall from your previous biology courses that glycolysis is just a process in cellular respiration that breaks down glucose to generate energy in the form of ATP. Notice in the image below, we're showing you a snippet of the glycolysis process or metabolic pathway. Over here on the far left, notice we are starting with a glucose molecule. One of the final products of glycolysis is the net generation of ATP. We're not showing the full glycolysis metabolic pathway here, but we will cover it later in our course. For now, we just want to emphasize that the cell already has plenty of ATP. And in that scenario, the cell would not want to be breaking down glucose to generate even more ATP. In this scenario, ATP can act as a negative feedback regulator to inhibit one of the enzymes that act in glycolysis, and this enzyme is known as phosphofructokinase, abbreviated as PFK. Phosphofructokinase or PFK is an allosteric enzyme that catalyzes a particular reaction in glycolysis. If we look below, notice that PFK catalyzes the conversion of fructose 6-phosphate into fructose 1,6-bisphosphate, essentially adding an extra phosphate group at this position. It needs to utilize ATP here as a co-substrate to catalyze this reaction. Again, PFK is going to be regulated via negative feedback by ATP. ATP can come back and negatively regulate PFK to inhibit it, essentially leading to the decrease of ATP or preventing the production of ATP. Because ATP is also utilized as a co-substrate for PFK, and ATP also acts as a negative allosteric regulator of PFK, that actually makes ATP a homotrophic allosteric effector. And that's because ATP is used as a substrate as well as an allosteric effector. Because the substrate is the same as the allosteric effector, that makes the allosteric effector homotrophic. This is just one example of negative feedback in glycolysis, but later in our course, we'll talk about a lot more examples of negative feedback throughout all of cellular respiration. But for now, this concludes our example of feedback regulation in glycolysis, and in our next video, we will be able to get some practice utilizing the concepts that we've learned. So I'll see you guys in that video.

The scheme below represents a hypothetical metabolic pathway for the synthesis of compound Y. The pathway is regulated by feedback inhibition. If S → T is the rate-limiting step, circle what the most likely inhibitor is and indicate with an arrow where the inhibition most likely occurs:
S → T → U → V → W → X → Y

So this practice problem says the scheme below shown right here represents a hypothetical metabolic pathway for the synthesis of compound y, and notice that compound y is the final product of this metabolic pathway. And so, it says this pathway is regulated by feedback inhibition, and we know from our previous lesson videos that feedback inhibition is also known as negative feedback. And so, if the reaction that converts molecule s into molecule t shown right here in the metabolic pathway is the rate-limiting step, which is recall the slowest step of the entire metabolic pathway, then circle what the most likely inhibitor is and indicate with an arrow where the inhibition most likely occurs. Now, because this particular reaction right here is the slowest rate-limiting step, it actually makes this reaction the key step to controlling this entire metabolic pathway because remember that a metabolic pathway can only proceed as fast as its slowest rate-limiting step. And so, because this is the key reaction, essentially, this reaction is going to be the reaction that we are going to want to regulate by feedback inhibition in order to control this entire metabolic pathway. And of course, because this is feedback inhibition, it's going to be represented by a negative sign like this. And so, now that we've determined exactly where the inhibition is most likely to occur, we are going to now circle the most likely inhibitor, and the most likely inhibitor of a metabolic pathway is going to be the final product. And so why here the final product is likely to be the allosteric inhibitor that regulates the enzyme that catalyzes this reaction right here. And so now that we've circled the most likely inhibitor and we've indicated with an arrow where the inhibition most likely occurs, this practice problem is complete, and so I'll see you guys in our next video.

Which of the following is TRUE about feedback inhibition?

• A. Feedback inhibition has no physiological importance.
• B. Sometimes multiple products are required for feedback inhibition.
• C. Feedback inhibition can only be accomplished by products from the same pathway by which they are formed.
• D. Feedback inhibition involves products binding to the active site to prevent enzyme activity.

Answer: (C)

Here’s what students ask on this topic:

What is negative feedback in biochemical reactions?

Negative feedback, also known as feedback inhibition, is a regulatory mechanism in biochemical reactions where the final product of a metabolic pathway inhibits an earlier step in the same pathway. This process helps prevent the overproduction and wasteful accumulation of the product. The inhibition typically occurs through the binding of the product to an allosteric site on an enzyme, which slows down the pathway and decreases the product's concentration. Once the product levels return to normal, the inhibition ceases, allowing the pathway to resume. This efficient regulation is crucial for maintaining cellular homeostasis.

How does negative feedback prevent overproduction in cells?

Negative feedback prevents overproduction in cells by allowing the final product of a metabolic pathway to inhibit an earlier step in the same pathway. When the concentration of the product becomes too high, it binds to an allosteric site on an enzyme involved in the pathway, reducing the enzyme's activity. This slows down the entire pathway, decreasing the production of the product. Once the product levels normalize, the inhibition stops, and the pathway can proceed again. This mechanism ensures that cells produce only the necessary amount of a product, avoiding waste and maintaining balance.

What role do allosteric enzymes play in negative feedback?

Allosteric enzymes play a crucial role in negative feedback by serving as the target for inhibition by the final product of a metabolic pathway. These enzymes have allosteric sites, distinct from their active sites, where the product can bind. When the product binds to the allosteric site, it induces a conformational change in the enzyme, reducing its activity. This decrease in enzyme activity slows down the metabolic pathway, leading to a reduction in the product's concentration. Once the product levels return to normal, the inhibition ceases, allowing the enzyme to regain its activity and the pathway to resume.

Can you provide an example of negative feedback in a metabolic pathway?

An example of negative feedback in a metabolic pathway is the regulation of the synthesis of isoleucine from threonine in bacteria. In this pathway, the final product, isoleucine, inhibits the activity of the first enzyme, threonine deaminase, by binding to its allosteric site. When isoleucine levels are high, it binds to threonine deaminase, reducing its activity and slowing down the pathway. This prevents the overproduction of isoleucine. Once isoleucine levels decrease, the inhibition is lifted, and threonine deaminase becomes active again, allowing the pathway to proceed and produce more isoleucine as needed.

Why is negative feedback important for cellular homeostasis?

Negative feedback is important for cellular homeostasis because it helps maintain the balance of biochemical reactions within the cell. By preventing the overproduction and wasteful accumulation of metabolic products, negative feedback ensures that cells produce only the necessary amounts of substances. This regulation is crucial for conserving energy and resources, avoiding toxic buildup of intermediates, and maintaining optimal conditions for cellular functions. Without negative feedback, cells could experience imbalances that disrupt metabolic processes and overall cellular health, leading to potential dysfunction or disease.