1. Chapter 18 Amino Acids, Proteins and Enzymes

2. Amino Acids 20 amino acids; all are α-amino acids:

3. 20 Amino Acids Essential AA’s –Isoleucine –Leucine –Lysine –Methionine –Phenylalanine –Threonine –Tryptophan –Valine –Arginine –Histidine Non-Essential AA’s –Alanine –Asparagine –Aspartate –Cysteine –Glutamate –Glutamine –Glycine –Proline –Serine –Tyrosine

4. Non-protein significance of AA’s –Tryptophan precursor for serotonin, melatonin and niacin Tryptophan Serotonin Melatonin Niacin –Glycine is a precursor for porphyrins such as heme Glycine Porphyrin Heme B

5. ‘Non-Protein’ Amino Acids β-Alanine –Carnosine β-alanyl-L-histidine –Anserine β-alanyl-N 1 -methyl-L-histidine –Glutathione γ-L-glutamyl-L-cysteinylglycine

6. Classification of AA R groups (Pg. 549) Nonpolar Side Chains –Proline: a secondary amine –Methionine: contains S –Tryptophan & Phenylalanine: aromatic rings Polar, Neutral Side Chains –Cysteine: S-H group –Tyrosine: aromatic ring Acidic Side Chains Basic Side Chains

7. Zwitterions Although  -amino acids are commonly written in the un- ionized form, they are more properly written in the zwitterion (internal salt) form. - Unionized form doesn’t exist in aqueous soln. or solid state - All have high melting pts - All are soluble in water COOH donates H to NH 2

8. 21 21-8 © 2003 Thomson Learning, Inc. All rights reserved Isoelectric Point Isoelectric point, pI: Isoelectric point, pI: the pH at which the majority of molecules of a compound in solution have no net charge

9. Handedness or Chirality All but one of the AA’s are of the L configuration, which means that their configuration around the central Carbon is similar to that of L- glyceraldehyde. “Left Handed” Stereocenter

10. Enantiomers Enantiomers (optical isomers): the 2 mirror image forms of a chiral molecule –Same formula but different arrangement ALL enantiomers are stereoisomers –Same formula, same chemical groups (COOH, NH 3, etc.) but different spatial arrangement (like cis-trans) Enantiomeric pairs differ in effect on polarized light.

11. Blue represents which atom? Red? White? Grey? Which AA is this? (Note: this is not the zwitterionic form)

12. Peptides and Polypeptides Peptide bond - Review Naming Conventions –Amino end (N-terminal)  Carboxyl end (C- Terminal) –‘yl’ added to name except to C-Terminal AA –Ser-gly-ala not the same as Ala-gly-ser Primary Structure = AA sequence

13. 21 21-13 © 2003 Thomson Learning, Inc. All rights reserved Primary Structure Primary structure: Primary structure: the sequence of amino acids in a polypeptide chain The number peptides derived from the 20 protein- derived amino acids is enormous there are 20 x 20 = 400 dipeptides possible there are 20 x 20 x 20 = 8000 tripeptides possible n 20 nthe number of peptides possible for a chain of n amino acids is 20 n for a small protein of 60 amino acids, the number of proteins possible is 20 60 = 10 78, which is possibly greater than the number of atoms in the universe!

14. 21 21-14 © 2003 Thomson Learning, Inc. All rights reserved Primary Structure Just how important is the exact amino acid sequence? human insulin consists of two polypeptide chains having a total of 51 amino acids; the two chains are connected by disulfide bonds in the table are differences between four types of insulin

15. 1 o Structure Crucial to Function Hemoglobin and Sickle Cell Anemia –Normal Hb: -Thr-Pro-Glu-Glu-Lys-Ala Position: 4 5 6 7 8 9 –Sickle Cell: -Thr-Pro-Val-Glu-Lys-Ala

16. 21 21-16 © 2003 Thomson Learning, Inc. All rights reserved Primary Structure vasopressin and oxytocin are both nonapeptides but have quite different biological functions vasopressin is an antidiuretic hormone oxytocin affects contractions of the uterus in childbirth and the muscles of the breast that aid in the secretion of milk

17. Primary Structure The ‘linear’ AA sequence Protein ‘Backbone’ consists of the alpha C, amino N and Carboxyl C. The 6 atoms, from alpha-C to alpha-C are arranged within an imaginary plane. –Important in 2 o structure

18. Shape-Determining Interactions in Proteins H-bonding along backbone R-group interactions –H-bonding –Hydrophobic interactions –Salt bridges –Covalent bonds S-S

19. 21 21-19 © 2003 Thomson Learning, Inc. All rights reserved Secondary Structure Secondary structure: Secondary structure: conformations of amino acids in localized regions of a polypeptide chain the most common types of secondary structure are  - helix and  -pleated sheet  -helix:  -helix: a type of secondary structure in which a section of polypeptide chain coils into a spiral, most commonly a right-handed spiral  -pleated sheet:  -pleated sheet: a type of secondary structure in which two polypeptide chains or sections of the same polypeptide chain align parallel to each other; the chains may be parallel or antiparallel Interaction: H-bonding along backbone

20. 21 21-20 © 2003 Thomson Learning, Inc. All rights reserved  -Helix Hydrogen bonds are between the C=O of peptide bond and the H-N of another peptide linkage 4 AA’s further along the chain. Grey = C Blue = N Red = O Yellow = R- group White = H

21. 21 21-21 © 2003 Thomson Learning, Inc. All rights reserved  -Pleated Sheet Grey = C Blue = N Red = O Yellow = R- group White = H

22. Beta-pleated sheet can be parallel or anti-parallel

23. Fibrous Proteins Fibrous Proteins (water-insoluble) –Water Insoluble –Secondary Structure determines nature Ex. Alpha-keratins –Hair, fingernails, wool –Composition of alpha-helixes; multiple strands twist together Ex. Fibroin –Silk –Composed of b-sheets

24. 21 21-24 © 2003 Thomson Learning, Inc. All rights reserved Collagen Triple Helix

25. Tertiary Structure Overall Conformation of a Peptide chain –How it folds, interactions between various AA’s along the chain. Determined by interactions of R-groups –Hydrophobic –Salt-bridges –H-bonds –disulfide

26. Example of a Globular Protein

27. Myoglobin –Conjugated Globular Protein Contains a heme group

28. 21 21-28 © 2003 Thomson Learning, Inc. All rights reserved Quaternary Structure Quaternary structure: Quaternary structure: the arrangement of polypeptide chains into a noncovalently bonded aggregation the individual chains are held in together by hydrogen bonds, salt bridges, and hydrophobic interactions Hemoglobin adult hemoglobin:adult hemoglobin: two alpha chains of 141 amino acids each, and two beta chains of 146 amino acids each each chain surrounds an iron-containing heme unit fetal hemoglobin:fetal hemoglobin: two alpha chains and two gamma chains; fetal hemoglobin has a greater affinity for oxygen than does adult hemoglobin

29. 21 21-29 © 2003 Thomson Learning, Inc. All rights reserved Hemoglobin

30. Chemical Properties of Proteins Hydrolysis – breaking of peptide bonds –By enzymes –By acid Denaturation – disruption of non-covalent bonds –Heat –Mechanical agitation –Detergents –pH change Disrupt salt-bridges –Solvents Disrupt hydrophobic interactions