Enzymes

2,854 views
2,359 views

Published on

Bettleheim

0 Comments
1 Like
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total views
2,854
On SlideShare
0
From Embeds
0
Number of Embeds
68
Actions
Shares
0
Downloads
58
Comments
0
Likes
1
Embeds 0
No embeds

No notes for slide
  • Memory molecule. PKMz sustains long-term memory in the cerebral cortex of rats
  • Enzymes

    1. 1. Chapter 23: Enzymes Chem 104 K. Dunlap
    2. 2. Enzymes Ribbon diagram of cytochromecoxidase, the enzyme that directly uses oxygen during respiration.
    3. 3. Enzyme Catalysis Enzyme: A biological catalyst. – With the exception of some RNAs that catalyze their own self-cleavage, all enzymes are proteins. – Enzymes can increase the rate of a reaction by a factor of 109 to 1020 over an uncatalyzed reaction. – Some catalyze the reaction of only one compound. – Others are stereoselective; for example, enzymes that catalyze the reactions of only L-amino acids. – Others catalyze reactions of specific types of compounds or bonds; for example, trypsin catalyzes hydrolysis of peptide bonds formed by the carboxyl groups of Lys and Arg.
    4. 4. Enzyme Catalysis Trypsincatalyzes the hydrolysis of peptide bonds formed by the carboxyl group of lysine and arginine.
    5. 5. Classification of Enzymes Enzymes are commonly named after the reaction or reactions they catalyze. – Example: lactate dehydrogenase, acid phosphatase. Enzymes are classified into six major groups according to the type of reaction catalyzed: – – – – Oxidoreductases: Oxidation-reduction reactions. Transferases: Group transfer reactions. Hydrolases: Hydrolysis reactions. Lyases: Addition of two groups to a double bond, or removal of two groups to create a double bond. – Isomerases:Isomerization reactions. – Ligases: The joining to two molecules.
    6. 6. Classification of Enzymes 1.Oxidoreductase: 2. Transferase: 3. Hydrolase:
    7. 7. Classification of Enzymes 4. Lyase: COO CH2 C-COOCH + H2O Aconitase COOCH2 C-COOHO C-H - COO- COO cis-Aconitate Isocitrate 5. Isomerase: CH2 OPO3 2Phosphohexose O isomerase OH OH HO OH a-D- Glucose-6-phosphate 6. Ligase: ATP + L-tyrosine + t-RNA CH2 OPO3 2O H HO H H HO CH2 OH OH a-D-Fructose-6-phosphate Tyrosine-tRNA synthetase L-tyrosyl-tRNA + AMP + PPi
    8. 8. Enzyme Terminology 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.
    9. 9. Schematic of an Active Site Schematic diagram of the active site of an enzyme and the participating components.
    10. 10. Terms in Enzyme Chemistry Activation: Any process that initiates or increases the activity of an enzyme. Inhibition: Any process that makes an active enzyme less active or inactive. Competitive inhibitor: A substance that binds to the active site of an enzyme thereby preventing binding of substrate. Noncompetitive inhibitor: Any substance that binds to a portion of the enzyme other than the active site and thereby inhibits the activity of the enzyme.
    11. 11. Enzyme Activity Enzyme activity: A measure of how much a reaction rate is increased. We examine how the rate of an enzymecatalyzed reaction is affected by: – Enzyme concentration. – Substrate concentration. – Temperature. – pH.
    12. 12. The effect of enzyme concentration on the rate Substrate concentration, temperature, and pH are constant.
    13. 13. The effect of substrate concentration on the rate Enzyme concentration, temperature, and pH are constant.
    14. 14. The effect of temperature on the rate Substrate and enzyme concentrations and pH are constant.
    15. 15. The effect of pH on the rate Substrate and enzyme concentrations and temperature are constant.
    16. 16. Lock-and-key model - The enzyme is a rigid three-dimensional body. – The enzyme surface contains the active site.
    17. 17. Induced Fit The active site becomes modified to accommodate the substrate.
    18. 18. Competitive Inhibition When a competitive inhibitor enters the active site, the substrate cannot enter.
    19. 19. Noncompetitive Inhibition The inhibitor binds itself to a site other than the active site (allosterism), thereby changing the conformation of the active site. The substrate still binds but there is no catalysis.
    20. 20. Enzyme kinetics in the presence and the absence of inhibitors.
    21. 21. Mechanism of Action – Both the lock-and-key model and the induced-fit model emphasize the shape of the active site. – However, the chemistry of the active site is the most important. – Just five amino acids participate in the active site in more than 65% of the enzymes studied to date. – These five are His > Cys > Asp > Arg > Glu. – Four of these amino acids have either acidic or basic side chains; the fifth has a sulfhydryl group (-SH).
    22. 22. Catalytic Power • Enzymes provide an alternative pathway for reaction. (a) The activation energy profile for a typical reaction. (b) A comparison of the activation energy profiles for a catalyzed and uncatalyzed reactions.
    23. 23. Enzyme Regulation Feedback control: An enzyme-regulation process where the product of a series of enzymecatalyzed reactions inhibits an earlier reaction in the sequence. – The inhibition may be competitive or noncompetitive.
    24. 24. Enzyme Regulation • Proenzyme (zymogen): An inactive form of an enzyme that must have part of its polypeptide chain hydrolyzed and removed before it becomes active. – An example is trypsin, a digestive enzyme. – It is synthesized and stored as trypsinogen, which has no enzyme activity. – It becomes active only after a six-amino acid fragment is hydrolyzed and removed from the N-terminal end of its chain. – Removal of this small fragment changes not only the primary structure but also the tertiary structure, allowing the molecule to achieve its active form.
    25. 25. 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.
    26. 26. Enzyme Regulation • The allosteric effect. Binding of the regulator to a site other than the active site changes the shape of the active site.
    27. 27. Enzyme Regulation Effects of binding activators and inhibitors to allosteric enzymes. The enzyme has an equilibrium between the T form and the R form.
    28. 28. Enzyme Regulation Protein modification:The process of affecting enzyme activity by covalently modifying it. – The best known examples of protein modification involve phosphorylation/dephosphorylation. – Example: Pyruvatekinase (PK) is the active form of the enzyme; it is inactivated by phosphorylation to pyruvatekinase phosphate (PKP).
    29. 29. Enzyme Regulation Isoenzyme (Isozymes): An enzyme that occurs in multiple forms; each catalyzes the same reaction. – Example: lactate dehydrogenase (LDH) catalyzes the oxidation of lactate to pyruvate. – The enzyme is a tetramer of H and M chains. – H4 is present predominately in heart muscle. – M4 is present predominantly in the liver and in skeletal muscle. – H3M, H2M2, and HM3 also exist. – H4 is allosterically inhibited by high levels of pyruvate while M4 is not. – H4 in serum correlates with the severity of heart attack.
    30. 30. Enzyme Regulation The isozymes of lactate dehydrogenase (LDH). The electrophoresis gel depicts the relative isozyme types found in different tissues.
    31. 31. Enzymes Used in Medicine Insert Table 23.2, page 648
    32. 32. Transition-State Analogs • Transition state analog: A molecule whose shape mimics the transition state of a substrate. • Figure 23.17 The prolineracemase reaction. Pyrrole-2-carboxylate mimics the planar transition state of the reaction (next screen).
    33. 33. Transition-State Analog
    34. 34. Transition-State Analogs • Abzyme: An antibody that has catalytic activity because it was created using a transition state analog as an immunogen. (a) The molecule below is a transition analog for the reaction of an amino acid with pyridoxal-5’-phosphate. (b) The abzyme is then used to catalyze the reaction on the next screen.
    35. 35. Transition-State Analogs

    ×