8.1 (Topic 1) Flashcards
Contrast metabolic chain reaction pathways with cyclical reaction pathways.
Most metabolic pathways involve a chain of reactions. (e.g. the conversion of phenylalanine into fumarate and acetoacetate, which can be used as energy sources in respiration). Some metabolic pathways form a cycle rather than a chain. In this type of pathway, the end product of one reaction is the reactant that starts the rest of the pathway.
Define activation energy.
The energy that is necessary for a reaction to occur as it is used to break or weaken the bonds in the substrates.
Explain the role of enzymes in lowering the activation energy of a reaction.
When an enzyme catalyzes 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. This 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).
Define enzyme inhibitor.
Substances that bind to enzymes and lower their activity.
Contrast competitive and noncompetitive enzyme inhibition.
Competitive enzyme inhibition:
- Competitive inhibitors have a similar structure to the substrate.
- Competitive inhibitors bind to the active sit
- Competitive inhibitors block substrate binding to the active site. The substrate and the inhibitor cannot simultaneously bind to the enzyme
- Increasing the concentration of the substrate lessens the effect of a competitive inhibitor.
Non-competitive enzyme inhibition:
- Non-competitive inhibitors do not have a similar structure to the substrate.
- Non-competitive inhibitors bind to a site on the enzyme that is not the active site. These are called allosteric sites.
- Non-competitive inhibitors binding causes the active site to change shape. The substrate may not be able to bind to the active site or the substrate can bind but the rate of reaction is slowed.
- increasing the concentration of the substrate has no effect on the non-competitive inhibitor.
Outline one example of a competitive enzyme inhibitor and one example of a noncompetitive enzyme inhibitor.
Competitive inhibitor example: Malonate inhibits succinate dehydrogenase (Krebs cycle) Non competitive inhibitor example: cyanide is a non-competitive inhibitor of cytochrome oxidase (electron transport chain).
Describe allosteric regulation of enzyme activity.
End-product inhibition involves the end product of the pathway (e.g. isoleucine) inhibiting the enzyme (e.g. threonine deaminase) catalyzing the first step of a metabolic pathway. The mechanism allows the concentration of the end-product produced to be controlled. The end-product is a non-competitive inhibitor and it binds to an allosteric site on the enzyme, reducing the activity of the enzyme. Enzymes with allosteric sites are called allosteric enzymes. If the end-product accumulates, it will inhibit its own production. If the concentration of the end-product is low, inhibition is reduced and production increases. This is an example of negative feedback. End-product inhibition also avoids the build up of intermediates.
Outline the mechanism and benefit of end-product inhibition.
This mechanism allows the concentration of the end-product produced to be controlled, it would be wasteful to continue making a substance that is not needed. Also, reactions often do not go to completion. Instead, an equilibrium position is reached with a characteristic ratio of substrates and products. So, if the concentration of products increases, a reaction will eventually slow down and stop. This effect reverberates back through a metabolic pathway when the end product accumulates, with all the intermediates accumulating. End-product inhibition prevents this build-up of intermediate products.
Illustrate end-product inhibition of the threonine to isoleucine metabolic pathway.
- Isoleucine is an essential amino acid in humans, can’t be synthesized in our bodies.
- Threonine attaches to threonine deaminase and produces products which gets modified a few more times before producing isoleucine, which can act as an allosteric inhibitor to the deaminase.
State the consequence of an increase in isoleucine concentration.
As the concentration of isoleucine builds up, it binds to the allosteric site of the first enzyme in the chain, threonine deaminase, thus acting as a non-competitive inhibitor.
Outline the reasons for the development of new anti-malarial drugs.
(Malaria is a disease caused by the pathogen Plasmodium falciparum.) The increasing resistance of P. falciparum to antimalarial drugs such as chloroquine, the dependence of all new drug combinations on a narrow range of medicines, and increasing global efforts to eradicate malaria all drive the need to develop new anti-malarial drugs
Explain the use of databases in the identification of potential new antimalarial drugs.
Plasmodium falciparum strain 3D7 is a variety of the malarial parasite for which the genome has been a sequence
Explain why the rate of reaction with increasing substrate concentration is lower with a non-competitive inhibitor compared to a competitive inhibitor.
In the presence of a competitive inhibitor, when the concentration of substrate begins to exceed the amount of inhibitor, the maximum rate of the uninhibited enzyme can be achieved; however, it takes a much higher concentration of the substrate to achieve this maximum rate. In the presence of a non-competitive inhibitor, 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. Those enzymes that do not bind to inhibitors follow the same pattern as the normal enzyme. It takes approximately the same concentration of enzyme to reach the maximum rate, but the maximum rate is lower than the uninhibited enzyme.
State two methods for determining the rate of enzyme controlled reactions.
- Measuring the rate of disappearance of a substrate or the rate of appearance of a product.
- Example: use iodine to test the presence of starch as iodine turns blue/black if starch is present. Have one drop of iodine into each well. Every 30 seconds, place a drop of the starch buffer solution into the iodine solution. Continue until there is no colour change of the iodine solution when combined with the buffer solution.
State the unit for enzyme reaction rate.
- The reaction rate is the amount of reaction over time.
- Amount of reaction / per unit time.
