1. Molecular Interactions in Cell events (i) Catalysis (ii) The Sodium-Potassium Pump (iii) Cell Signalling

2. What caused this?

3. That’s clever Bombardier Beetles  Oxygen gas formed during break down of H 2 O 2 forces out water and other chemicals  Reaction releases a lot of heat so the water comes out as steam

4. A reminder of their importance Catalase breaks down 5 million molecules of H 2 O 2 per minute at 0 o C, to protect cells. It would take 300 years to break down the same number of molecules using iron as a catalyst

5. Chemical Reactions Synthesis (anabolic)  Condensation reactions Removal of water to form a bond Degradation (catabolic)  Hydrolysis reactions Addition of water to break a bond

6. Enzymes Proteases  Hydrolyse peptide bonds  break down proteins into amino acids Nucleases  Hydrolyse phosphodiester bonds  Break down nucleic acids into nucleotides ATPases  Hydrolyse ATP  Break ATP into ADP and P i with the release of energy

7. Enzymes continued…. Kinases  Catalyse the transfer of a phosphate group onto a molecule such as a carbohydrate or a protein

8. Specificity of enzymes Compare the two diagrams Think about your knowledge of proteins tertiary structure? Why do you think the induced fit model is favoured?

9. Specificity of enzymes Induced-fit model  When substrate combines with the enzyme it causes a change in shape of the active site  The change in shape results in an optimal fit for the substrate-enzyme interaction  Once the product diffuses away, the enzyme returns to its original shape

10. What analogy could be applied to this model?

11. What do the following have in common? Arsenic Nerve Gases  Tabun  Sarin Mercury Cyanide DDT Lead Cadmium

12. Cyanide Cyanide is found is a gas (sometimes liquid) Used / found in  House fires  Apricot stones  Suicide pills  Gas chambers (both US and Nazi Germany)  Stock piled by US and Soviet Union in 50’s and 60’s  Mining  Photography  Electroplating

13. Cyanide Binds to iron atom in the enzyme cytochrome C oxidase This changes the shape of the enzyme Knowing how this works has important applications for  Detection of poisoning  Treatment

14. Control of enzyme activity - Inhibitors Competitive Inhibitors  Decrease the rate of reaction  Inhibitor is similar in structure and electrical charge to substrate  It binds to the active site  An increase in the substrate can result in an increase of product formation (inhibitor is out competed)  Competitive inhibition can be reversible or irreversible (depending on mechanism of binding)

15. Inhibitors cont.. Competitive inhibitors cont…

16. Inhibitors cont… Non-competitive inhibitors  Decrease the rate of reaction  Inhibitors have no similarity to the substrate  Inhibitor binds to part of the enzyme (other than the active site) distorting the shape of the enzyme  Increase in substrate concentration does not increase product formation  Can also be reversible

17. Inhibitors cont… Non-competitive inhibition cont….

18. Control of enzymes – Enzyme modulators Allosteric enzymes  Allosteric enzymes have at least one other binding site than the active site (called an allosteric site)  Allosteric enzymes have 2 forms – active and inactive  When a substance binds to an allosteric site it changes the shape of the active site.  Positive modulation The modulator changes the active site so the enzyme becomes active (substrate fits) Positive modulators are activators

19. Enzyme modulators cont… Allosteric enzymes cont…  Negative modulation The modulator changes the active site so the enzyme becomes inactive Negative modulators are inhibitors

20. Enzyme modulators cont…. Allosteric enzymes cont…

21. Control of enzymes – Covalent modifications  Addition, modification or removal of a variety of chemical groups  Changes the shape of the enzyme Phosphorylation and dephosphorylation  Kinase enzymes add phosphate  Phosphatase enzymes remove phosphate  Some enzymes are activated by phosphorylation, others are inactivated (and vice versa for dephosphorylation)

22. Covalent modifications cont… Proteolytic cleavage  Conversion of an inactive enzyme to an active one  Example Trypsinogen – Trypsin  Trypsinogen is synthesised in the Pancreas  Activation occurs when trypsinogen has amino acids removed in the duodenum by another protease enzyme  This changes the trypsinogen into the active form trypsin  Trypsin then helps to activate more trypsinogen molecules

23. Back to cyanide What type of inhibition is demonstrated by cyanide in the inhibition of cytochrome oxidase? Enzyme inhibition is often how drugs work – targeting enzymes specific to other organisms, not humans

24. Control of metabolic pathways End product inhibition  Chemical reactions are normally organised into metabolic pathways with enzymes controlling each chemical reaction  The end-product can act as a negative modulator, binding to the first enzyme preventing the metabolic pathway from proceeding because intermediary substrates are not produced  This is a process of negative feedback

25. Learning Activities Read and take notes from DART pg 61-68 Scholar 6.3 and 6.4 Check out http://highered.mcgraw- hill.com/sites/0072437316/student_view0/chapter8/animations.ht ml#http://highered.mcgraw- hill.com/sites/0072437316/student_view0/chapter8/animations.ht ml# Find examples for each type of enzyme control Use flash cards to remember the enzymes and their reactions Draw posters of each type of enzyme control Use the information on ‘end-product inhibition in respiration’ to demonstrate the principle of negative feedback ‘Enzymes’ worksheet ‘Enzyme cofactors and inhibitors’ worksheets Advanced Higher Biology Questions