CHAPTER 15 ENZYMES

1. CHAPTER 15 ENZYMES

2. Enzymes provide an alternative pathway for reaction, one with a significantly lower activation energy and, therefore, a faster rate.

3. Terms in Enzyme Chem • Apoenzyme: the protein part of an enzyme. • Cofactor: a nonprotein portion of an enzyme that is necessary for catalytic function; examples are metallic ions such as Zn2+ and Mg2+. • Coenzyme: a nonprotein organic molecule, frequently a B vitamin, that acts as a cofactor. • Substrate: the compound or compounds whose reaction an enzyme catalyzes. • Active site: the specific portion of the enzyme to which a substrate binds during reaction.

5. SPECIFICITY • How selective an enzyme is for a substrate or reaction. • High Specificity – ie. Thrombin • Low Specificity – ie. Papain

6. Thrombin clips two peptides from fibrinogen. This produces the fibrin monomer with exposed polymerization sites that can bind to other fibrin monomers. The monomers polymerize to form a loose clot.

7. Used as meat tenderizer • Treatment for jellyfish, bee and wasp stings • Used in contact lens solutions • Breaks down the protein in toxins, venoms and bacteria

8. Mechanism of Action • Lock-and-key model of enzyme mechanism. • The enzyme is a rigid three-dimensional body. • The enzyme surface contains the active site.

9. Mechanism of Action • Induced-fit model • The active site becomes modified to accommodate the substrate.

11. Enzyme Activity • Enzyme activity: a measure of how much a reaction rate is increased. • We examine how the rate of an enzyme-catalyzed reaction is effected by: • enzyme concentration • substrate concentration • temperature • pH

12. Enzyme Activity • The effect of enzyme concentration on the rate of an enzyme-catalyzed reaction. Substrate concentration, temperature, and pH are constant.

13. Enzyme Activity • The effect of substrate concentration on the rate of an enzyme-catalyzed reaction. Enzyme concentration, temperature, and pH are constant.

14. Enzyme Activity • The effect of temperature on the rate of an enzyme-catalyzed reaction. Substrate and enzyme concentrations and pH are constant.

15. Enzyme Activity • The effect of pH on the rate of an enzyme-catalyzed reaction. Substrate and enzyme concentrations and temperature are constant.

16. 1 2 6 4 5 3 Feedback – Regulation by end product of a reaction on an earlier step

18. Enzyme Regulation • Allosterism: enzyme regulation based on an event occurring at a place other than the active site but that creates a change in the active site. • An enzyme regulated by this mechanism is called an allosteric enzyme. • Allosteric enzymes often have multiple polypeptide chains. • Negative modulation: inhibition of an allosteric enzyme. • Positive modulation: stimulation of an allosteric enzyme. • Regulator: a substance that binds to an allosteric enzyme.

19. The Allosteric Effect • The allosteric effect. Binding of the regulator to a site other than the active site changes the shape of the active site.

20. ZYMOGENS/PROENZYMES • Enzyme made in inactive form • Change to the enzyme makes it active • Digestion and blood coagulation

21. Thrombin clips two peptides from fibrinogen. This produces the fibrin monomer with exposed polymerization sites that can bind to other fibrin monomers. The monomers polymerize to form a loose clot.

22. ENZYME INHIBITION • Reversible • Noncompetitive – Inhibitor does not bind at the active site (ieallosteric control) • Competitive – Inhibitor binds at the active site

23. Competitive Inhibition

25. Treatment of HIV With AZT

26. Competitive Inhibition Noncompetitive Inhibition

27. Irreversible Inhibition • Inhibitor binds at active site and forms covalent bond with amino acid side groups involved in catalysis. • Most toxins and poisons • Many pharmaceuticals

28. Heavy Metal Poisoning (Hg and Pb) -CH2-SH + Hg or Pb -CH2-S-Hg Pb Lead poisoning may have caused years of chronic illness in composer Ludwig van Beethoven and may have contributed to his death. Chemical analysis experts found unusually high levels of lead in strands of Beethoven's hair.

29. Lead in the Environment • Homes built prior to 1977 are likely to contain lead-based paint. • Soil near heavily-used streets and roads may contain lead because lead was used in gasoline until the 1970’s. • Lead may get into drinking water from materials used in plumbing, such as pipes. • Lead-glazed or lead-painted pottery, leaded crystal, and some inks

30. Tar Creek Site

31. Mercury in the Environment Predator fish including tuna, mackeral, shark and swordfish “Mad as a Hatter” was a common expression in the 1800’s.

32. -CH2-OH Nerve Gases + Nerve Gas (X) -CH2-O-X Binds to the active site of acetylcholinesterase so acetylcholine is not broken down to acetyl CoA and choline, acetylcholine builds up in the synapse and jams nerves in the "on" position so they constantly signal muscles to contract.

33. -CH2-OH + -CH2-O-

34. Antibiotics All penicillin derivatives inhibit bacterial cell wall synthesis. If cell walls are improperly made it allows water to flow into the cell causing it to burst. The structure of a complex between penicillin G and the Streptomyces transpeptidase.

35. Genetic Control Best for adapting to environmental or developmental changes