7.6 Enzymes (AHL)

1. 7.6 Enzymes (AHL) Pp 210 - 213 Pp 69 -71

2. Metabolic pathways • Metabolic reactions often occurs in small step reactions with a number of intermediate products in-between • Metabolic reactions includes: • Catabolic reactions such as respiration & • Anabolic reactions such as photosynthesis • Each step in a metabolic pathway each is unique & requires its own enzyme to allow finer control of metabolic pathway

3. A Biochemical Pathway

4. Induced-fit model • lock & Key hypothesis does not explain the broad specificity of some enzymes • the molecular shape of active sites is not always complementary to that of the substrate • induced-fit model attempts to over come these difficulties • when substrate binds to the enzyme, the shape of active site changes to accommodate the substrate • bonds in substrate weaken & activation energy decreases • the structure of the enzyme allows for a certain amount of adaptation to the substrate, this explains broad specificity of some enzymes such as proteases

5. Effect of enzymes on activation energy • Enzymes lower the activation energy of the chemical reaction that they catalyse- Ea • In the activated complex or transition state energy is put into the substrate to weaken the structure. This allow the reaction to occur with a minimal amount of additional energy required. • Normal activation energy would denature the proteins of the cell. Thus reduced activation energy make these reactions possible in a cell. • After the product is formed energy is released– ΔG • Exergonic reactions release more energy than the activation energy

6. Competitive and non-competitive inhibition • Inhibitors are substances that reduce or completely stop the action of an enzyme • Inhibitor can attach on the active site (competitive inhibitor) or on another region of the enzyme molecule other than the active site(non-competitive inhibitor)

7. Comparing competitive and non-competitive inhibition of enzymes • both types of inhibitor reduce enzyme activity • both types of inhibitor bind to the enzyme • both types of inhibitor prevent the substrate from binding to the active site

8. Difference between competitive and non-competitive inhibition Competitive inhibition Non-competitive inhibition • example: succinate dehydrogenase is inhibited by malonate • substrate and inhibitor are chemically similar & have same shape • inhibitor binds to active site • inhibitor does not change the shape of the active site • increases in substrate concentration reduce the inhibition • example: pyruvate kinase is inhibited by alanine • substrate and inhibitor are chemically not similar & have different shape • inhibitor binds away from the active site i.e. at allosteric site • inhibitor changes the shape of the active site • increases in substrate concentration do not affect the inhibition

9. Control of metabolic pathways by end-product inhibition • end-product inhibition is an example of negative feedback • it controls rate of product synthesis i.e. amount of product produced • when there is too much of end-products, the product inhibits the enzyme that catalyses the 1st reaction (allosteric enzyme) • the product binds to the enzyme at an allosteric site i.e. site other than the active site • enzyme changes shape & the substrate cannot bind to the active site • binding of inhibitor to an allosteric site is reversible i.e. when the inhibitor detaches, the active site returns to the original shape & substrates can bind again • end-product inhibition controls the metabolic pathway by switching on & off the initial stage of the metabolic pathway based on the concentration of end-product • e.g. ATP inhibition of phosphofructokinase, in glycolysis

10. Feedback Inhibition of Biochemical Pathways

11. Revision Questions • Describe the induced-fit model of enzymes. • Outline how enzymes lower the activation energy of the chemical reactions that they catalyse. • With reference to one example of each, distinguish between competitive and non-competitive inhibition. • Explain the control of metabolic pathways by end-product inhibition.