Feedback Inhibition

Feedback Inhibition Definition

Feedback inhibition is a cellular control mechanism in which an enzyme’s activity is inhibited by the enzyme’s end product. This mechanism allows cells to regulate how much of an enzyme’s end product is produced.

Most biochemical processes are complex and multi-step, requiring multiple enzymes to get from the starting substrate to the desired end product.

Typically, feedback inhibition acts on the first enzyme unique to a given pathway. For example, in the case of amino acid production, an amino acid may act as an inhibitor for the first enzyme in the pathway whose purpose is making more of that amino acid.

The graphic below illustrates this process:

Feedback inhibition is usually accomplished through something called an “allosteric site” – a site on an enzyme that changes the shape of an enzyme, and subsequently the behavior of the active site.

The root words of allosteric come from the Greek “allo” for “other,” and the greek “stereos,” for “space.” This may help you to remember that “allosteric sites” cause enzymes to take on “other forms,” or “other spaces.”

Binding of a regulatory messenger – in this case, the end product of the biochemical pathway – to the allosteric site changes the shape of the whole enzyme.

In feedback inhibition, binding of the end product to the allosteric site slows down or stops the enzyme’s activity so that little or no new end product is produced. When levels of the end product drop, the enzyme will encounter fewer particles of the end product and its activity will increase again.

Feedback inhibition prevents waste that occurs when more of a product is made than the cell needs. It can also prevent harm when having too much of the pathway’s end product may actually be harmful to the organism.

The result of feedback inhibition is This allows them to adjust their rate of reaction depending on how much of their end product is needed, and prevent their end product from building up to dangerous levels.

One example of this that takes place in our own bodies is the production of cholesterol. Cholesterol in small amounts is useful to our cells’ membranes, but in large amounts, it can build up in our veins and arteries and become very harmful.

Modern diets often result in dangerously high cholesterol as a result of eating too much of it – but in nature, it was sometimes necessary for our bodies to make their own cholesterol.

The mechanism of cholesterol production in the liver is inhibited by presence of cholesterol in the blood. Large amounts of cholesterol in the blood actually prevents liver cells from transcribing the necessary mRNA to make the enzyme that makes cholesterol.

So when we eat high-cholesterol diets, our livers produce less cholesterol than they would if we were not getting enough cholesterol from our food.

In some people, dangerously high cholesterol can be a result of this feedback inhibition pathway getting turned off – resulting in the body continuing to produce its own cholesterol in addition to what is consumed.

Function of Feedback Inhibition

Feedback inhibition allows the body to avoid many potentially dangerous situations, including:

Waste. Without feedback inhibition, energy or raw materials that could be used for important cellular functions might be wasted on unnecessary ones.
Prevents depletion. Without feedback inhibition, raw materials and energy might be depleted by biochemical processes that don’t stop, even when their end product is not needed. A good example of this is the production of ATP from glucose. The enzymes that produce ATP from glucose are subject to feedback inhibition by ATP. This saves glucose by preventing its unnecessary breakdown when the cell has plenty of ATP.
Prevents dangerous build-up. The end products of some biochemical pathways can actually be dangerous in high concentrations. Cholesterol is an excellent example of something our body can make that is good in small quantities but dangerous in large quantities.
Maintain homeostasis. An essential function of life is the ability to maintain constant internal circumstances in the face of changing environmental circumstances. Some chemical messengers that are involved in maintaining homeostasis are regulated through feedback regulation.

Examples of Feedback Inhibition

Production of ATP

ATP is created from glucose via a series of enzymatic reactions in our cells. Glucose is a stable form of energy currency, which can be absorbed from food or transported around the body as needed. ATP, on the other hand, is unstable, and will spontaneously lose its energy if it sits around un-used.

For this reason, it’s important to regulate the breakdown of glucose and the production of ATP. Producing too much ATP results in energy loss, and glucose depletion could mean big trouble in circumstances where food is scarce.

To control the amount of glucose that is broken down to produce ATP, the first enzyme in this breakdown chain is allosterically regulated by ATP. If ATP binds to this enzyme, it will not break down further glucose.

This allows cells to produce lots of ATP in circumstances where ATP is being used quickly, meaning it is depleted; but produce little in circumstances where little ATP is needed, leading to a buildup of ATP within the cell.

In this way our bodies make very efficient use of their energy, storing it in the stable form of glucose until it is needed.

Production of Amino Acids

The human body uses twenty different amino acids – the “building blocks” of protein. All amino acids share some common features, and some are very similar to each other. This means that different amino acids are made from the same raw materials.

However, the cell may need different amino acids at different times. Some cells need to make large amounts of proteins that consist of just one or two amino acids; others may need all of the amino acids, or the same cell may need different amino acids at different times.

This means that just like converting glucose to ATP, cells must find a way to efficiently use their raw materials to make exactly what they need at any given time. And just like with ATP, they use feedback regulation to ensure they produce only the amino acids they need at any given time.

The first unique step in the biochemical pathway for each amino acid – called the “committed step,” because at that point the cell is “committed” to using the raw material to produce the amino acid – is allosterically regulated by the amino acid itself.

So when there is a lot of taurine in a cell that isn’t being used, for example, that serine will bind to the first enzyme in the pathway that makes more serine. As a result, more serine will not be made until the cell’s serine levels drop.

In this way, cells ensure that raw materials are available for making the amino acids they need – and that they are not consumed by making amino acids they don’t need.

Production of Cholesterol

Cholesterol is used in cell membranes, where it helps to maintain thentegrity of the cell membrane and facilitate signaling between cells. For this reason, our body has the ability to make cholesterol if it is not found in the environment.

However, if too much cholesterol is found in the body, it can build up in arteries and veins and cause deadly cardiovascular disease.

For this reason, it is important for the body to be able to reduce cholesterol production under circumstances when we are getting a lot of cholesterol from our diets.

In the case of cholesterol, allosteric regulation is of a transcription factor that leads to more cholesterol-producing enzyme being made. When a lot of cholesterol is present in the blood, no new cholesterol-producing enzyme is made, which leads to a fall in cholesterol over time.

Some cases of dangerously high cholesterol are caused by failure of this feedback inhibition mechanism, resulting in large amounts of cholesterol being made by the liver even though there is already a large amount of cholesterol present in the body.

Active Site – The site of an enzyme where it catalyzes the transformation of one or more substrates into an end product.
Allosteric Site – A site on an enzyme that changes the enzyme’s shape and activity when a molecule, such as a feedback inhibitor, binds to it.
Enzyme – A protein that catalyzes the chemical change of one or more substrates into one or more products. Enzymes drastically increase the speed of chemical reactions, making life as we know it possible.

Quiz

1. Which of the following would NOT qualify as feedback inhibition?
A. An enzyme is inhibited by its own end product.
B. The first enzyme in a biochemical pathway is inhibited by the end product of the last enzyme in the pathway.
C. The cell detects that there is too much of a substance in its cytoplasm, so it makes a chemical messenger to inhibit the enzyme that’s making it.
D. None of the above.

Answer to Question #1

C is correct. In feedback inhibition, a biochemical pathway is inhibited by its own end product. In scenario C., the enzymes are not being inhibited by their own end product, but by a separate signaling mechanism.

2. Which of the following scenarios would NOT benefit from feedback inhibition?
A. A cell needs to produce varying amounts of ATP according to its energy needs; but it doesn’t want to produce too much ATP because that would result in energy waste.
B. A cell needs to be able to produce the right amino acids at the right time, instead of using its materials to produce amino acids it doesn’t need.
C. An organism needs to be able to produce cholesterol when it is not supplied by the diet, but must be able to shut cholesterol production off when the diet is high in cholesterol.
D. An organism must produce as much fat as possible to stay warm in the coming winter.

Answer to Question #2

D is correct. In this scenario, the animal needs to produce as much fat as possible, so it would not make sense to have feedback inhibition of fat production.

3. Which of the following basic functions of life does feedback inhibition help to sustain?
A. Reproduction – The ability to make more of oneself.
B. Homeostasis – The ability to maintain a stable internal environment even as the outside environment changes.
C. Growth – The ability to grow in size or cell number.
D. Nutrition – The ability to take in materials from the environment for energy and raw materials.

Answer to Question #3

B is correct. While feedback inhibition can help with all life functions by keeping the organism alive, it helps most directly with homeostasis. Feedback inhibition assists organisms in maintaining their environments in a constant state even in the face of changing environmental demands.