8.1 Metabolism Flashcards
How do enzymes work?
- Lower the energy required to reach the transition state, they lower the activation energy.
- When an enzyme catalyses a reaction, the substrate binds to the active site and is altered to reach the transition state. It is then converted into the products which separate from the active site. The binding lowers the overall energy level of the transition state. The activation energy of the reaction is therefore reduced. The net amount of energy released by the reaction is unchanged by the involvement of the enzyme. However as the activation energy is reduced, the rate of reaction is greatly increased, typically by a factor of a million or more.
What are inhibitors?
Some chemical substances bind to enzymes and reduce their activity, these are called inhibitors.
What are competitive inhibitors?
Competitive inhibitors interfere with the active site so that the substrate cannot bind. The inhibitor takes the place of the substrate.
What are non-competitive inhibitors?
Non competitive inhibitors bind at a location other than the active site, this results in a change of shape in the enzyme so that the enzyme cannot bind to the substrate.
On a rate of reaction vs substrate concentration graph, which lines would be normal enzymes, competitive inhibitors and non-competitive inhibitors?
The rate of reaction for a normal enzyme would increase with a steep gradient at first and then the gradient would decrease but still be increasing and then come to a straight line where increasing the concentration has no effect on the rate.
The rate of reaction for a competitive enzyme would increase with a more consistent gradient, but less steep than the normal enzyme, then it would reach the same point and go flat the same. It would increase more gradually rather than fast then slow. This is because the inhibitor and substance are competing for space in the active site, and so the rate is much slower to begin with, however when the amount of substrate greatly exceeds the amount of inhibitor it is able to reach the same as the normal enzyme. This is why is it much less steep to begin with and is a slower rate but catches up towards the end. It is almost like a diagonal line. Whereas the normal enzyme is like an r.
The rate of reaction of a non-competitive inhibitor rises much less steeply and only reaches half of the height of the competitive and non-competitive inhibitors. The enzyme does not reach the same maximum rate because the binding of the non-competitive inhibitor prevents some of the enzymes from being able to react regardless of substrate concentration.
Explain end-product inhibition?
Metabolic pathways can be controlled by end-product inhibition.
Many enzymes are regulated by chemical substances that bind to special sites on the enzyme away from the active site. These are called allosteric interactions and the binding site is called an allosteric site. In many cases, the enzyme catalyses one of the first reactions in the pathway and the product at the end of the pathway acts as the inhibitor.
This means that the reaction is turned off when there is lots of product and no more is needed, but it turned on to make more when it is used up. This helps to set up an equilibrium to balance products and reactants. It is therefore economical. It also prevents the build up of intermediate products.
What are allosteric sites?
Sites in an enzyme that are not the active site.
What is an example of end-product inhibition?
Through a series of five reactions, the amino acid threonine is converted to isoleucine. As the concentration of isoleucine builds up, it binds to an allosteric site of the first enzyme (threonine deaminase) and stops making more isoleucine.
How can we investigate metabolism?
Developments in scientific research are because of improvements in computing. Developments in bioinformatics, such as the interrogation of databases, have facilitated research into metabolic pathways.
Bioinformatics is an approach where lots of scientists can enter information into a database and then other scientists can query it. It has helped research into metabolic pathways, this is referred to as chemogenomics.
This is particularly useful in developing new drugs. You can test the effect of drugs on metabolism, so you can make a huge library of chemicals individually on a range of different organisms.
How are chemogenomics used today?
It was used to identify potential new malaria drugs.
We need to keep investigating anti-malarial drugs because the malarial bacteria is becoming resistant to several of them. You can test the genome (by screening) against chemicals, both the resistant and non-resistant malaria bacteria and see if they exhibit metabolism.
- By doing this with malaria, they found 19 new chemicals that inhibit the enzymes normally inhibited by anti-malarials. This provides new information to research.
