1. Chapter 15 Biomolecules: Amino Acids, Peptides, and Proteins
Suggested Problems: 22,24,29,32-3,44-5,47

2. Proteins – Amides from Amino Acids
Amino acids contain a basic amino group and an acidic carboxyl group
Joined as amides between the –NH2 of one amino acid and the –CO2H of the next amino acid
Chains with fewer than 50 units are called peptides
Protein: larger chains that have structural or catalytic functions in biology

3. 26.1 Structures of Amino Acids
In neutral solution, the —COOH is ionized and the — NH2 is protonated
The resulting structures have “+” and “–” charges (a dipolar ion, or zwitterion)
They are internal salts and resemble ionic salts in solution

4. React with Acid or Base Amino acids are amphiprotic
Can react with either acids or bases

5. The Common Amino Acids 20 amino acids form amides in proteins
All are -amino acids - the amino and carboxyl are connected to the same C
They differ by the other substituent attached to the  carbon, called the side chain, with H as the fourth substituent
Proline is a five-membered secondary amine, with N and the  C part of a five-membered ring
Other side chains may be acidic, basic, or neutral
All amino acids except proline contain primary amines.

6. Abbreviations and Codes
Alanine A, Ala
Arginine R, Arg
Asparagine N, Asn
Aspartic acid D, Asp
Cysteine C, Cys
Glutamine Q, Gln
Glutamic Acid E, Glu
Glycine G, Gly
Histidine H, His
Isoleucine I, Ile
Leucine L, Leu
Lysine K, Lys
Methionine M, Met
Phenylalanine F, Phe
Proline P, Pro
Serine S, Ser
Threonine T, Thr
Tryptophan W, Trp
Tyrosine Y, Tyr
Valine V, Val

7. The 20 Common Amino Acids in Proteins
Glycine is the one amino acid which does not have a chiral center

8. The 20 Common Amino Acids in Proteins
Structures of amino acids

9. The 20 Common Amino Acids in Proteins
Structures of amino acids

10. The 20 Common Amino Acids in Proteins
Structures of amino acids

11. Types of side chains
Neutral: Fifteen of the twenty have neutral side chains
Asp and Glu have a second COOH and are acidic
Lys, Arg, His have additional basic amino groups side chains (the N in tryptophan is a very weak base)
Cys, Ser, Tyr (OH and SH) are weak acids that are good nucleophiles

12. Histidine
Contains an imidazole ring that is partially protonated in neutral solution
Only the pyridine-like, doubly bonded nitrogen in histidine is basic. The pyrrole-like singly bonded nitrogen is nonbasic because its lone pair of electrons is part of the 6  electron aromatic imidazole ring.

13. Chirality of Amino Acids
Glycine, 2-amino-acetic acid, is achiral
In all the others, the  carbons of the amino acids are centers of chirality
The stereochemical reference for amino acids is the Fischer projection of L-serine
Proteins are derived exclusively from L-amino acids

14. Essential Amino Acids
All 20 of the amino acids are necessary for protein synthesis
Humans can synthesize only 10 (nonessential) of the 20
The other 10 (essential) must be obtained from food

15. 15.2 Isoelectric Points
In acid solution, the carboxylate and amine are in their conjugate acid forms, an overall cation
In base solution, the groups are in their base forms, an overall anion
In neutral solution cation and anion forms are present
This pH where the overall charge is 0 is the isoelectric point, pI

16. 15.3 Peptides and Proteins
Proteins and peptides are amino acid polymers in which the individual amino acid units, called residues, are linked together by amide bonds, or peptide bonds
An amino group from one residue forms an amide bond with the carboxyl of a second residue
Since peptides and proteins are formed through the loss of water to form the peptide bond, the breakage of a peptide bond is referred to as hydrolysis.

17. Peptide Linkages
Two dipeptides can result from reaction between A and S, depending on which COOH reacts with which NH2 we get AS or SA
The long, repetitive sequence of NCHCO atoms that make up a continuous chain is called the protein’s backbone
Peptides are always written with the N-terminal amino acid (the one with the free NH2 group) on the left and the C-terminal amino acid (the one with the free CO2H group) on the right
Alanylserine is abbreviated Ala-Ser (or A-S), and serylalanine is abbreviated Ser-Ala (or S-A)

18. 15.4 Covalent Bonding in Peptides
Amide bond links in amino acids is the same as other amide bonds
Restricted rotation
Planar configuration with the N— H 180⁰ to the C=O

19. Disulfide Linkages RS—SR linkage between two cysteine residues
Formed by mild oxidation of RSH groups
Cleaved by mild reducing agents
RS—SR linkages can be inter- or intra-molecular

20. Disulfide Linkages in Insulin

21. 15.8 Protein Structure
Proteins are classified as either fibrous or globular proteins
Fibrous – polypeptide chains arranged side by side in long filaments
Connective tissue
Collagen in tendon
Myosin in muscles
Globular – coiled into compact spherical shapes
Mobile within cells
Soluble in water
Enzymes

22. Levels of Structure
The primary structure of a protein is simply the amino acid sequence.
The secondary structure of a protein describes how segments of the peptide backbone orient into a regular pattern. (a-helix and b-pleated sheet)
The tertiary structure describes how the entire protein molecule coils into an overall three-dimensional shape.
The quaternary structure describes how different protein molecules come together to yield large aggregate structures (more than one chain)

23. -Helix
-Helix stabilized by H-bonds between amide N–H groups and C=O groups four residues away

24. -Pleated Sheet
b-pleated sheet secondary structure is exhibited by polypeptide chains lined up in a parallel arrangement, and held together by hydrogen bonds between chains

25. Forces Involved in Tertiary Structure
Forces the same as those that act on all molecules
Hydrophilic
Hydrophobic
Determine the orientation on the interior or the exterior of the protein in an aqueous environment
Also important in stabilizing tertiary structure are
Disulfide bridge – between cysteine residues
Salt bridges – between positively and negatively charge amino acid residues

26. Forces Involved in Tertiary Structure

27. 15.9 Enzymes and Coenzymes
An enzyme is a protein that acts as a catalyst for a biological reaction.
Most enzymes are specific for substrates while enzymes involved in digestion, such as papain attack many substrates

28. Types of Enzymes by Function
Enzymes are usually grouped according to the kind of reaction they catalyze, not by their structures

29. 26.11 How Do Enzymes Work? Citrate Synthase
Citrate synthase catalyzes a mixed Claisen condensation of acetyl CoA and oxaloacetate to give citrate
Normally Claisen condensations require a strong base in an alcohol solvent but citrate synthase operates in neutral solution

30. The Structure of Citrate Synthase
Determined by X-ray crystallography
Enzyme is very large compared to substrates, creating a complete environment for the reaction

31. Mechanism of Citrate Synthetase
A cleft with functional groups binds oxaloacetate
Another cleft opens for acetyl CoA with H 274 and D 375, which have carboxylate that abstract a proton from acetyl CoA
The enolate (stabilized by a cation) adds to the carbonyl group of oxaloacetate
The thiol ester in citryl CoA is hydrolyzed

32. Mechanism of Citrate Synthetase

33. Sickle Cell Anemia
In sickle cell anemia a single amino acid difference is responsible for the sickling. A valine replaces a glutamate at position 6 on the surface of the beta chain. Under conditions of low oxygen concentration, the hemoglobin sickles and clumps together in the smaller vessels.