Chapter Twenty One

1. Chapter Twenty One Enzymes and Vitamins

2. Enzymes • _____________ for biological reactions • Proteins • Lower the __________ _________ • ___________ the rate of reaction • Have specific shapes that ______ the ___________ of reactants • Activity lost if _____________ • May be simple __________ or complex • May contain _________________ such as metal ions or __________ _____________

3. Names of Enzymes • End in –ase • Identifies a reacting substance sucrase – reacts sucrose lipase - reacts lipid • Describes function of enzyme oxidase – catalyzes oxidation hydrolase – catalyzes hydrolysis • Common names of digestion enzymes still end –in pepsin, trypsin

4. Classification of Enzymes Class Reactions catalyzed • Oxidoreductoases oxidation-reduction • Transferases transfer group of atoms • Hydrolases hydrolysis • Lyases add/remove atoms to/from a double bond • Isomerases rearrange atoms • Ligases combine molecules using ATP

5. Examples of Enzyme Classification • Oxidoreductoases oxidases - oxidize reductases – reduce • Transferases transaminases – transfer amino groups kinases – transfer phosphate groups • Hydrolases proteases - hydrolyze peptide bonds lipases – hydrolyze lipid ester bonds • Lyases carboxylases – add CO2 hydrolases – add H2O

6. Enzyme Structure • The shape/structure of enzymes is related to their functions • Simple enzymes • Enzymes that consist only of protein • Conjugated enzymes • Enzymes that consist of protein and a nonprotein part • Apoenzyme + cofactor = holoenzyme • Coenzyme: small organic molecule that serves as a cofactor in a conjugated enzyme (needed to prepare the active site for catalytic activity)

7. Vitamins • __________ compounds that are essential for the proper functioning of the human body • Many function as cofactors • ___________ be synthesized by the human body • Must be obtained from dietary sources • Two main ___________: • Water-soluble • Fat soluble

8. Water-Soluble Vitamins • Soluble in aqueous solutions • Used as cofactors by many enzymes • Not store in the body • Vitamin C • Vitamin B

9. Fat-Soluble Vitamins • Vitamins A, D, E, and K • Soluble in lipids, but not in aqueous solutions • Important in vision, bone formation, antioxidants, and blood clotting • Stored in the body

14. Enzyme Action • An enzyme binds a substrate in a region called the _____________ _________ • Only certain substrates can fit the _________ ____________ • Amino acid R groups in the active site help substrate bind and align correctly • Enzyme-substrate ____________ forms • Substrate reacts to form product • Product is released

15. The active site of an enzyme can be a crevice-like region formed as a result of the protein’s secondary and tertiary structural characteristics.

16. Enzyme Specificity • Enzymes may recognize and catalyze: • 1. A single substrate: ___________ Specificity • Example: Urease (only catalyzes the hydrolysis of urea) • 2. A single stereoisomer: Stereochemical Specificity • Example: L-amino-acid oxidase (catalyzes the oxidation of L-amino acids, but not D-amino acids)

17. Enzyme Action: Lock and Key Model • In the lock and key model of enzyme action: • The active site has a rigid shape • Only substrates with the matching shape can fit • The substrate is a key that fits the lock of the active site

18. Enzyme Action: Lock and Key Model

19. Lock and Key Model + + E + S ES complex E + P P S S P

20. Enzyme Specificity • Enzymes may recognize and catalyze: • 3. A group of similar substrates: Group Specificity • Example: Hexokinase (adds a phosphate to hexoses) • 4. A particular type of bond: Linkage Specificity • Example: Chymotrypsin (catalyzes the hydrolysis of peptide bonds)

21. Enzyme Action: Induced Fit Model • Enzyme structure flexible, not rigid • Enzyme and active site adjust shape to bind substrate • Increases range of substrate specificity • Shape changes also improve catalysis during reaction

22. Enzyme Action

23. Enzyme Action: Induced Fit Model • E + S ES complex E + P P S S S P

25. Enzyme Activity

26. Factors Affecting Enzyme Action: Temperature • Little activity at low temperature • Rate ____________ with temperature • Most active at optimum temperatures (usually 37°C in humans) • Activity lost with ______________ at ______ temperatures

27. Factors Affecting Enzyme Activity: pH • Maximum activity at optimum pH • Narrow range of activity • Most lose activity in low or high pH • Why is one pH better than another? • R groups of amino acids have proper charge at certain pH values • Tertiary structure of enzyme is correct

28. Factors Affecting Enzyme Activity: Substrate Concentration • Increasing substrate concentration increases the rate of reaction (enzyme concentration is constant) • Maximum activity reached when all of enzyme combines with substrate

29. Factors Affecting Enzyme Activity: Enzyme Concentration • The rate of reaction increases as enzyme concentration increases (at constant substrate concentration) • At higher enzyme concentrations, more substrate binds with enzyme

31. Enzyme Inhibition Inhibitors • Molecules that cause a ________ of catalytic activity • Change the protein structure of an enzyme to prevent substrates from fitting into the active sites • May be “competitive” or “noncompetitive” • Some effects are irreversible

32. Competitive Inhibition A competitive inhibitor • Has a structure similar to substrate • Occupies active site • Competes with substrate for active site • Has effect reversed by increasing substrate concentration http://www.eccentrix.com/members/chempics/Slike/Enzyme/2Competitive_inhibition.jpg

33. Noncompetitive Inhibition A noncompetitive inhibitor • Does not have a structure like substrate • Binds to the enzyme but not active site • Changes the shape of enzyme and active site • Substrate cannot fit altered active site • No reaction occurs • Effect is not reversed by adding substrate • Substrate activity is restored when inhibitor is no longer bonded to the enzyme

36. Heavy metal poisoning is an example of noncompetitive inhibition of an enzyme.

37. Irreversible Inhibition • In irreversible inhibition, a substance destroys enzyme activity by bonding with R groups at the active site • Inhibitor permanently blocks substrate binding • One of the ways antibiotics kill bacteria

38. Sulfa Drugs Structures of selected sulfa drugs in use today as antibiotics.

40. Regulating Enzyme Activity • Four main mechanisms to regulate enzyme activities • Genetic Control • Feedback Control • Zymogen Activation • Allosteric Regulation • Activation – Positive Regulation • Deactivation – Negative Regulation

41. Feedback Control • In feedback control: • A product of a reaction acts as a negative regulator • An end product binds with the first enzyme in a sequence when sufficient product is present E1 E2 E3 A  B  C  D Inhibition of enzyme 1 by product D

42. Zymogens • Inactive forms of enzymes • Activated when one or more peptides are removed • Example: Proinsulin is converted to insulin by removing a small peptide chain • Digestive enzymes are produced in one organ as zymogens, but not activated until they are needed; Ex. trypsinogen / trypsin

43. Allosteric Enzymes An enzyme with two or more protein chains (quaternary structure) and two kinds of binding sites (substrate and regulator) Activity is influenced by “regulators” (found or produced in cells normally) Positive regulator Enhances the binding of substrate and accelerates the rate of reaction Negative regulator Prevents the binding of the substrate to the active site and slows down the rate of reaction

44. Enzymes and Vitamins • Levels of enzymes in blood used as a diagnostic tool.

45. Diagnostic Enzymes • The levels of diagnostic enzymes determine the amount of damage in tissues

47. Enzymes and Vitamins