CHAPTER 21: Amino Acids, Proteins, & Enzymes General, Organic, & Biological Chemistry

1. CHAPTER 21: Amino Acids, Proteins, & Enzymes General, Organic, & Biological Chemistry Janice Gorzynski Smith

2. CHAPTER 21: Amino Acids, Proteins, Enzymes • Learning Objectives: • The 20 common, naturally occurring Amino Acids • stereochemistry • acid/base chemistry • Peptides • Formation • N & C terminals • Proteins • Primary, Secondary, Tertiary, Quaternary structure • Hydrolysis and denaturation • Enzymes • Catalysis • Inhibitors • Zymogens • CH 21 Homework: • End of Chapter problems: 32, 36, 38, 42, 48, 50, 52, 62, 64, 68, 70, 74, 77, 81, 93, 94 Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed.

3. Amino Acids Definition All amino acids contain two functional groups—an amino group (NH2) and a carboxyl group (COOH). Amino acids differ in the R group bonded to the α carbon Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed.

4. Amino Acids At isoelectric pH • The isoelectric point for amino acids is about 6, this is the pH at which the amino acid exists as a neutral molecule • The pKa of the amine group is usually about 9-11 • The pKa of the carboxylic acid group is usually about 2-3 Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed.

5. Amino Acids Acid/Base Chemistry Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed.

6. Amino Acids Stereochemistry • Carbohydrates: naturally occurring isomer is the D-isomer (OH group on right in a Fischer projection) • Amino Acids: most naturally occurring isomers are the L-isomer (NH3 group on the left in a Fischer projection) Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed.

7. The 20 common & naturally occurring amino acids in humans. Essential Amino Acids: Isoleucine (Ile) Leucine (Leu) Methionine (Met) Phenylalanine (Phe) Threonine (Thr) Tryptophan (Trp) Valine (Val) Arginine (Arg) Histidine (His) Lysine (Lys)

8. Peptides Definition • Peptides and proteins are formed when amino • acids are joined together by amide bonds. • A dipeptide has two amino acids joined together • by one amide bond. • The amide bond is called a peptide bond. • Polypeptideshave many amino acids, while • proteins have more than 40 amino acids. Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed.

9. Peptides Amide Bond Formation Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed.

10. Peptides Amide Bond Formation Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed.

11. Peptides N & C Terminal Amino Acids • The amino acid with the free –NH3+group is the • N-terminal amino acid and is written on the left. • The amino acid with the free –COO−group is the • C-terminal amino acid and is written on the right. Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed.

12. Peptides/Protein Insulin Gly-Ile-Val-Glu-Gln-Cys-Cys-Thr-Ser-Ile-Cys-Ser-Leu-Tyr-Gln-Leu-Glu-Asn-Tyr-Cys-R Phe-Val-Asn-Gln-His-Leu-Cys-Gly-Ser-His-Leu-Val-Glu-Ala-Leu-Tyr-Leu-Val-Cys-Gly-Glu-Arg-Gly-Phe-Phe-Tyr-Thr-Pro-Lys-Thr-R’ Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed.

13. Proteins Primary Structure The primary structure of a protein is the sequence of amino acids joined together by peptide bonds. Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed.

14. Proteins Secondary Structure • The secondary structure is the 3D arrangement of localized regions of a protein. • These regions arise due to hydrogen bonding between the N—H group of one amide with the C═O group of another. Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed.

15. Proteins Secondary Structure Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed.

16. Proteins Tertiary Structure • The tertiary structure is the 3D shape adopted by the entire peptide chain: • Maximize Hydrogen bonding with water (hydrophilic) • Stabilize non-polar sidechains by london dispersion forces (hydrophobic) • Polar functional groups H-bond with each other • Charged sidechains attracted through electrostatic interactions • Disulfide bonds form Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed.

17. Proteins Tertiary Structure Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed.

18. Proteins Quaternary Structure The quaternary structure of the protein is the shape adopted when two or more folded poly-peptide chainscome together into one complex. Ex: Potassium Channel: Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed.

19. Proteins Quaternary Structure Hemoglobin Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed.

20. Proteins Quaternary Structure Hemoglobin Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed.

21. Proteins 1°, 2°, 3°, 4° Structure Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed.

22. Proteins Peptide Hydrolysis Protein hydrolysis involves breaking the peptide bondsby treatment with aqueous acid, base, or certain enzymes: Pepsin (gastric juices), Trypsin and Chymotrypsin (intestines) Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed.

23. Proteins Peptide Denaturation Denaturationis the process of altering the shape of a protein without breaking the amide bonds that form the primary structure: heat, acid, base, or agitation Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed.

24. Enzymes Definition • Enzymes are proteins that serve as biological catalysts for reactions in all living organisms. • They increase the rate of a reaction (106 to 1012times faster), but are unchanged themselves. • Enzymes are very specific; each enzyme catalyzes a certain reaction or type of reaction only. • The names of most enzymes end with the suffix “-ase” like peptidase, lipase, and hydrolase • A cofactoris a metal ion or an organic molecule needed for an enzyme-catalyzed reaction to occur. Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed.

25. Enzymes Function http://leavingbio.net/enzymes.htm

26. Enzymes Conformational Changes Upon Binding http://plantcellbiology.masters.grkraj.org/html/Plant_Cell_Biochemistry_And_Metabolism1-Proteins_And_Enzymes.htm

27. Enzymes Inhibition http://o.quizlet.com/i/WRLW8kdWLDOY1YZbEdKgyA_m.jpg

28. Enzymes HIV Protease Inhibitor Protease inhibitors are designed to mimic a peptide linkage (-NH-CO-) but replaces the linkage with a –CH2-CH(OH)- which binds to the active site but the protease cannot cleave a linkage so it stays bound. Saquinavir: http://en.wikipedia.org/wiki/Discovery_and_development_of_HIV-protease_inhibitors

29. Enzymes Lipoxygenase Inhibitor Zileuton is an asthma maintenance medication that inhibits 5-lipoxygenase, therefore, inhibiting leukotriene formation. http://en.wikipedia.org/wiki/Zileuton

30. Enzymes Differences in Binding Sites Superoxide Reductase: SOR Hydrophilic Binding Pocket Superoxide Dismutase: SOD Hydrophobic Binding Pocket Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed.

31. Enzymes Mechanistic Differences: SOR vs SOD SOD Mechanism SOR Mechanism H2O Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed.

32. Enzymes Zymogens Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed.