Chapter 8

1. Chapter 8 150-157

2. If all Exergonic Reactions happen spontaneously… …then how come all of them haven’t already happened?

3. Activation Energy! We need catalysts! Biological Catalysts Are Enzymes

4. Activation Energy C6H12O6 +O2 Activation Energy Energy Energy CO2 + H20 Reaction Time

6. Enzymes are Proteins • Organic catalysts - increase the rate of chemical reactions in cells. • Hold reactant molecules close together for reaction to occur- uses an active site. • The active site is used to bind the reactant molecules-substrate.

8. Substate Active site Enzyme Figure 8.16 (a) The active site: • Is the region on the enzyme where the substrate binds.

9. Enzyme- substrate complex (b) Figure 8.16 • Induced fit of a substrate: • Brings chemical groups of the active site into positions that enhance their ability to catalyze the chemical reaction

10. 1 Substrates enter active site; enzyme changes shape so its active site embraces the substrates (induced fit). 2 Substrates held in active site by weak interactions, such as hydrogen bonds and ionic bonds. 3 Active site (and R groups of its amino acids) can lower EA and speed up a reaction by • acting as a template for substrate orientation, • stressing the substrates and stabilizing the transition state, • providing a favorable microenvironment, • participating directly in the catalytic reaction. Substrates Enzyme-substrate complex 6 Active site Is available for two new substrate Mole. Enzyme 5 Products are Released. 4 Substrates are Converted into Products. Figure 8.17 Products The catalytic cycle of an enzyme

11. Conditions that Affect Protein Shape Can disrupt H bonds by: • High Temperature • pH Changes (Acidic or Basic) • Salt (or Ion) Concentration • Binding of Regulatory Molecules Disrupting the 2°, 3°, 4° structure is called denaturation.

12. Enzymes • Enzymes have a temperature optimum. • Too Cold - H bonds and van der Waals forces aren’t flexible enough to allow the induced fit for catalysis. • Too Hot - they are too weak to maintain the enzymes shape and break apart.

13. Most Human Enzyme Temp. Optimums Male Reprod. Enzymes Rate of Reaction 31 33 35 37 39 41 43 Rxn Temperature, °C

14. Siamese Cats and Pigment Enzymes 3 wks old 4 yrs. old

15. Pigment Enzymes in Harp Seal Pups

16. Most Human Enzyme pH Optimums Rate of Reaction Pepsin Trypsin 2 3 4 5 6 7 8 Rxn pH

17. Inhibitors and Activators • Inhibitors – are molecules (usually proteins) that bind to an enzyme and decrease its activity. • Two Kinds: • A. Competitive Inhibitors – compete for the same active site as the substrate; displaces some of the substrate. • B. Noncompetitive Inhibitors – bind to the enzyme in some other location other than its active site., changing its shape.

18. A substrate can bind normally to the active site of an enzyme. Substrate Active site Enzyme (a) Normal binding A competitive inhibitor mimics the substrate, competing for the active site. Competitive inhibitor Figure 8.19 (b) Competitive inhibition Enzyme Inhibitors • Competitive inhibitors • Bind to the active site of an enzyme, competing with the substrate

19. Competitive Inhibition

20. A noncompetitive inhibitor binds to the enzyme away from the active site, altering the conformation of the enzyme so that its active site no longer functions. Noncompetitive inhibitor (c) Noncompetitive inhibition Figure 8.19 Noncompetitive inhibitors • Bind to another part of an enzyme, changing the function

21. Noncompetitive Inhibitors • These inhibitors bind to a site other than the active site called the allosteric site (“other form”). • Chemical “on/off” switches. • Called Allosteric Inhibitor. • If a molecule binds to an allosteric site and keeps the enzyme in its active shape – Allosteric Activator.

22. Allosteric activaterstabilizes active from Allosteric enyzmewith four subunits Active site(one of four) Regulatorysite (oneof four) Activator Active form Stabilized active form Allosteric activaterstabilizes active form Oscillation Non-functionalactivesite Inhibitor Stabilized inactiveform Inactive form (a) Allosteric activators and inhibitors. In the cell, activators and inhibitors dissociate when at low concentrations. The enzyme can then oscillate again. Figure 8.20 Enzymes change shape when regulatory molecules bind to specific sites, affecting function

23. Another Look at Allosteric Inhibitors

24. Allosteric Activation

25. Things that help Enyzmes • Molecules that bind to the active site and HELP the enzyme’s function – Cofactor. • Often metal ions, vitamins, etc. • If cofactor is a nonprotein organic molecule- Coenzyme. • Coenzymes often serve as electron acceptors to help break bonds. • Coenzymes then transfer the electrons to other compounds. (Remember NAD+ and FAD+?

26. Enzymes Work with Co-Enzymes Captures H+

27. An Example of a Biochemical Pathway

28. Feedback Inhibition E1 E2 Substrate B Substrate A Substrate C E2 E1 Allosteric Inhibitor Substrate C

29. Initial substrate(threonine) Active siteavailable Threoninein active site Enzyme 1(threoninedeaminase) Isoleucineused up bycell Intermediate A Feedbackinhibition Active site of enzyme 1 no longer binds threonine;pathway is switched off Enzyme 2 Intermediate B Enzyme 3 Intermediate C Isoleucine binds to allosteric site Enzyme 4 Intermediate D Enzyme 5 Figure 8.21 End product(isoleucine) Feedback inhibition