This lesson will review enzymes, substrates and products, then give a definition of feedback inhibition and discuss how it works. Some examples of feedback inhibition will also be discussed.
Review of Enzymes
Ever made a cup from clay? We can use this activity as a metaphor for enzymes, substrates, and products. What are enzymes? Enzymes are proteins that speed up the change of substrates into products. Substrates are cellular materials, rather like the clay. Products are what substrates become. Clay, representing substrate, can be shaped, heated, and glazed to make a useable cup, which represents the product. Pieces of the clay are removed or added where necessary to achieve the finished product, the cup.
The same thing happens to substrates – some chemical groups may be added or removed to make the final product. The enzyme binds its substrate at the active site and that is where substrate becomes product. There are many steps that the clay must go through to become a cup. A lump of clay is first molded into shape. The cup shape is just the first product. The cup is then fired to make it solid, then glazed to give it decoration. Products formed are often used as substrates for other enzymes.
At each step, a different product is formed and the substrate is changed from what it was before. The cell uses enzymes at each step to make the next product. Like clay, the amino acid threonine, for example, is shaped and changed by various enzymes in a stepwise process to make the amino acid isoleucine.
Enzymes are very important in speeding up product formation. The products of enzymes can have positive and negative effects on the cell and thus good or bad effects on an organism. Therefore, it is important that enzymes be regulated and stop product formation if and when they are told to do so.
Feedback inhibition, or end-product inhibition, is when a product in a pathway goes back and tells one of the previous enzymes to stop.
If you are making a lot of cups, eventually the room will be filled with finished cups. When you run out of space, you can think of the abundance of finished cups as telling you to stop, that you no longer need to shape the clay.
Cells use products to tell enzymes to slow down or stop changing substrate to product. But it’s not just enzymes that products can act upon. Products can also bind factors (like repressor proteins) and prevent the transcription of genes that ultimately make the products, thus feedback inhibition can also extend to the genetic level.
Enzymes that are not properly regulated can lead to diseased states. Sialuria, for example, is a disorder that results from a disrupted enzyme regulation. The improper regulation can cause various problems, including upper respiratory infections, dehydration, upset stomach, seizures and learning disabilities. Normally, the enzyme causing this disorder is regulated through a mechanism known as feedback inhibition. Without this regulation, the disorder occurs.
Products that feed back and inhibit enzymes that are ultimately responsible for their formation bind a site other than the active site. This site is known as the allosteric site. After products bind to inhibit, the enzyme often changes its form and temporarily loses its ability to attach to a substrate.
There are also instances where different end products are required to stop enzyme activity, rather like a defensive lineman trying to tackle the guy with the ball. One person may slow down the guy with the ball, but not stop him. Sometimes it takes many defensive linemen jumping on the guy with the ball to completely halt his progress. Products in a pathway can gang up on enzymes in a similar manner, one slowing the enzyme and many completely halting the progress of product formation.
Feedback inhibition can span many pathways as well. The product from one pathway can be used as a substrate for other pathways. The products from that second pathway can return and stop an enzyme in the first pathway from functioning. For example, if you sell your cups, they may be used by tableware distributors as part of a cup and saucer set. If there only two saucers and ten cups, the distributor may come back to you and tell you to stop making that cup until it is needed again.
There are many steps to change the amino acid threonine into isoleucine, and the first enzyme involved is threonine deaminase. This pathway is one example that involves feedback inhibition. When there is an abundance of isoleucine, the isoleucine attaches to the first enzyme – threonine deaminase – and stops its activity. In essence, isoleucine is preventing its own formation
Feedback inhibition is also involved in regulating the amount of pyrimidines available for the formation of new DNA. The first step in pyrimidine synthesis involves the enzyme ATCase. One of the products – CTP (or Cytidine TriPhosphate) – inhibits ATCase to prevent the overproduction of pyrimidines.
Citrate inhibition of the enzyme phosphofructokinase-1 is an example where one pathway product feeds back and inhibits another. Citrate formed in the citric acid cycle acts as an inhibitor for the formation of pyruvate in the glycolytic pathway.
On a broader scope, feedback inhibition is involved in many pathways, like hormone regulation, and can affect various aspects of physiology including blood pressure, blood sugar levels, appetite and menses.
Enzymes are proteins that bind substrates at the active site and speed up their conversion to products. Products can act as substrates for other enzymes and can also regulate enzymes. Feedback inhibition is a form of enzyme regulation whereby products prevent product formation by binding to an allosteric site and inhibiting enzyme activity.
The product acting as an inhibitor can be a result of the same pathway used to create it or from another pathway. Sometimes multiple products are required to completely stop an enzyme from functioning. Isoleucine, CTP, and citrate are all examples of products that are used in feedback inhibition. Physiologically, feedback inhibition is an important form of enzyme regulation and is also involved in genetic regulation.