Chapter 13 Introduction to Enzymes

1. Chapter 13 Introduction to Enzymes Read pages 459 – 466 & 470 Chymotrypsin with bound substrate

2. Enzymes • Enzymes are the agents of metabolic function • Enzymes endow cells with the remarkable capacity to exert kinetic control over thermodynamic potentiality

3. Properties of Enzymes (1) High reaction rates (2) Catalyze reactions at physiological conditions (milder reaction conditions) (3) Have a high degree of specificity (e.g. only A is converted to B) (4) Can be regulated (e.g., A is only converted to B under certain conditions)

4. Catalytic Power • Enzymes can accelerate reactions as much as 1016over uncatalyzed rates! • Urease is a good example: • Catalyzed rate: 3x104/sec • Uncatalyzed rate: 3x10 -10/sec • Ratio is 1x1014 !

5. Some enzymes achieve remarkable catalytic efficiency

6. Glycolysis

8. Enzyme catalyzed reactions are much faster than the corresponding uncatalyzed reaction E + S ES EP E + P

9. S P Activation energies Biochemical free energy change at pH 7.0

10. Function of DNA ligase Enzyme Substrate(s)Product(s)

11. Coenzymes Cofactors may be metal ions (such as Zn2+ required for the catalytic activity of carboxypeptidase A) Coenzymes are organic molecules (such as the NAD+ in YADH)

12. Metal Cofactors

14. Organic Cofactors (also called coenzymes)

15. Other cofactors • Known as prosthetic groups • Permanently attached with their protein • Often by covalent bonds • Example: Heme in hemoglobin

16. Specificity • Enzymes selectively recognize proper substrates over other molecules • Enzymes produce products in very high yields - often much greater than 95% • Specificity is controlled by structure - the unique fit of substrate with enzyme controls the selectivity for substrate and the product yield

17. An enzyme-substrate complex Illustrates both the geometrical & physical complementarity between enzymes and substrates

18. Stereospecificity Enzymes are highly specific in both in binding chiral substrates & in catalyzing their reactions. Stereospecificity arises because enzymes virtue of their inherent chirality. Proteins consists of only L-amino acids.

19. E + S ES EP E + P The enzyme binding site Induced fit mechanism is most prevalent in enzymes. The enzyme active site adapts its structure to interact with the substrate & transition states. The same set of non-covalent interactions that enable a protein to fold are involved in stabilizing the interaction between the substrate and enzyme.

20. How do enzymes accelerate reactions? • Chemical reactions between the substrate and functional groups on the enzyme can provide alternative, lower-energy reaction pathways. (Example:group transfer through an intermediate with the group transiently covalently attached to the enzyme) 2. Binding energy, DGB, is a major source of free energy used by enzymes to lower the activation energies of reactions.