Chapter 3 Amino Acids and Peptides PDF

Chapter 3 Amino Acids and Peptides © 2018 Cengage Learning. All Rights Reserved. Chapter Outline (3-1) Amino acids are three-dimensional (3-2) Structures and properties of amino acids (3...

Chapter 3 Amino Acids and Peptides © 2018 Cengage Learning. All Rights Reserved. Chapter Outline (3-1) Amino acids are three-dimensional (3-2) Structures and properties of amino acids (3-3) Amino acids can act as both acids and bases (3-4) The peptide bond (3-5) Small peptides with physiological activity © 2018 Cengage Learning. All Rights Reserved. 3-1 Amino Acids Are Three-Dimensional Amino acids - Include Figure 3.1 - The General Formula of Amino Acids, Showing the Ionic an amino group and a Forms That Predominate at pH 7 carboxyl group, both of which are bonded to the -carbon Amino group: —NH2 functional group Carboxyl group: — COOH functional group that disassociates to give the carboxylate anion, —COO–, and a hydrogen ion © 2018 Cengage Learning. All Rights Reserved. Figure 3.2 - Stereochemistry of Alanine and Glyceraldehyde The amino acids found in proteins have the same chirality as L- glyceraldehyde, which is opposite to that of D-glyceraldehyde. -carbon Bonded to a hydrogen and to the side chain group, R. Side chain group: Portion of an amino acid that determines its identity. Two stereoisomers of amino acids are designated as L- and D-amino acids based on similarity to glyceraldehyde Stereoisomers: Molecules that differ from each other only in their configuration. © 2018 Cengage Learning. All Rights Reserved. 3-2 Structure and Properties of Amino Acids Except for glycine, all amino acids have at least one chiral center (the -carbon) and are chiral (stereoisomers) Vast majority of -amino acids have the L configuration at the -carbon Proline is usually in the L form Side chain carbons in amino acids other than glycine are designated with Greek symbols, starting at - carbon (β-, γ-, δ-, ε-, and ω-the terminal carbon). Amino acids can be frequently referred to by three-letter or one-letter abbreviations of their names, with the one-letter designation being much more prevalent; Table 3.1 lists these abbreviations. © 2018 Cengage Learning. All Rights Reserved. Table 3.1 - Names and Abbreviations of the Common Amino Acids © 2018 Cengage Learning. All Rights Reserved. Nonpolar Amino Acids One group of amino acids has nonpolar side chains. This group consists of glycine, alanine, valine, leucine, isoleucine, proline, phenylalanine, tryptophan, and methionine (9 A.A). Alanine, valine, leucine, and isoleucine contain aliphatic hydrocarbon group Proline has an aliphatic cyclic structure (imino acid). In phenylalanine, the hydrocarbon group is aromatic In tryptophan, the side chain contains an indole ring, which is aromatic In methionine, the side chain contains a sulfur atom in addition to aliphatic hydrocarbon groupings © 2018 Cengage Learning. All Rights Reserved. Figure 3.3 - Structures of the Amino Acids Commonly Found in Proteins The 20 amino acids that are the building blocks of proteins can be classified as (a) nonpolar (hydrophobic), (b) polar, (c) acidic, or (d) basic. Also shown are the three-letter and one-letter codes used to denote amino acids. For each amino acid, the ball-and-stick model (left) and the space-filling model (right) show only the side chain (except for proline, where the entire ring structure is shown). © 2018 Cengage Learning. All Rights Reserved. Polar-Neutral Amino Acids Another group of amino acids has polar side chains that are electrically neutral at neutral pH. This group includes serine, threonine, tyrosine, cysteine, glutamine, and asparagine (6 A.A). Glycine is sometimes included here for convenience since it lacks a nonpolar side chain. In serine and threonine, the polar group is a hydroxyl (—OH) bonded to aliphatic hydrocarbon groups In tyrosine, the hydroxyl group (phenol) is bonded to an aromatic hydrocarbon group In cysteine, the polar side chain contains a thiol group (—SH) Glutamine and asparagine contain amide groups in their side chains © 2018 Cengage Learning. All Rights Reserved. Figure 3.3 - Structures of the Amino Acids Commonly Found in Proteins (continued 1) The 20 amino acids that are the building blocks of proteins can be classified as (a) nonpolar (hydrophobic), (b) polar, (c) acidic, or (d) basic. Also shown are the three-letter and one-letter codes used to denote amino acids. For each amino acid, the ball-and-stick model (left) and the space-filling model (right) show only the side chain (except for proline, where the entire ring structure is shown). © 2018 Cengage Learning. All Rights Reserved. Acidic Amino Acids Two amino acids glutamic acid and aspartic acid have carboxyl groups in their side chains in addition to the one present in all amino acids. A carboxyl group can lose a proton, forming the corresponding carboxylate anion. Because of the presence of the carboxylate, the side chain of each of these two amino acids are negatively charged at neutral pH. © 2018 Cengage Learning. All Rights Reserved. Figure 3.3 - Structures of the Amino Acids Commonly Found in Proteins (continued 2) © 2018 Cengage Learning. All Rights Reserved. Basic Amino Acids Three amino acids-histidine, lysine, and arginine- have basic side chains, and the side chain in all three is positively charged at or near neutral pH 7. In lysine, side-chain amino group is attached to an aliphatic hydrocarbon tail. In arginine, the side-chain basic group, the guanidino group bonded to an aliphatic hydrocarbon tail, is more complex in structure than amino group. In free histidine, the pKa of the side-chain imidazole group is 6.0, which is not far from the physiological pH. © 2018 Cengage Learning. All Rights Reserved. Figure 3.3 - Structures of the Amino Acids Commonly Found in Proteins (continued 3) © 2018 Cengage Learning. All Rights Reserved. Example 3.1 - Structures and Properties of Amino Acids 1. In the following group, identify the amino acids with nonpolar side chains and those with basic side chains: Alanine, serine, arginine, lysine, leucine, and phenylalanine 2. The pKa of the side-chain imidazole group of histidine is 6.0. What is the ratio of uncharged to charged side chains at pH 7.0? © 2018 Cengage Learning. All Rights Reserved. Example 3.1 - Solution Amino acids with nonpolar and basic side chains Nonpolar - Alanine, leucine, and phenylalanine Basic - Arginine and lysine Serine is not in either category because it has a polar side chain Ratio of uncharged to charged side chains at pH 7.0 The ratio is 10:1 because the pH is one unit higher than the pK. © 2018 Cengage Learning. All Rights Reserved. Uncommon Amino Acids Derived from the common The structures of the parent amino acids—proline for hydroxyproline, lysine amino acids for hydroxylysine, and tyrosine for Produced through thyroxine—are shown for comparison. All amino acids are shown in their posttranslational predominant ionic forms at pH 7. modification Parent amino acid is modified after the protein is synthesized by an organism Hydroxylysine and hydroxyproline are found only in a few connective- tissue proteins, such as collagen Thyroxine is found only in the thyroid gland © 2018 Cengage Learning. All Rights Reserved. 3-3 Amino Acids can act as both acids and bases In a free amino acid, carboxyl group (negative) and amino group (positive) are charged at neutral pH. Amino acids without charged groups on their side chains exist in neutral solution as zwitterions with no net charge. A zwitterion has equal positive and negative charges; in solution, it is electrically neutral. Neutral amino acids do not exist in the form NH2-CHR-COOH( i.e., without charged groups). Titration of Amino Acids. See Fig. 3.5 © 2018 Cengage Learning. All Rights Reserved. Figure 3.5 - The Ionization of Amino Acids A. The ionic forms of the amino acids, shown without consideration of any ionizations on the side chain. The cationic form is the low-pH form, and the titration of the cationic species with base yields the zwitterions and finally the anionic form. B. The ionization of histidine (an amino acid with a titratable side chain). © 2018 Cengage Learning. All Rights Reserved.  What happens when we titrate an amino acid? When an amino acid is Figure 3.6 - The Titration titrated, its titration curve Curve of Alanine represents the reaction of each functional group with a hydrogen ion. Fig. 3.6 The titration curve of alanine is that of a diprotic acid. Fig. 3.7 The titration curve of histidine is that of a triprotic acid. © 2018 Cengage Learning. All Rights Reserved. Figure 3.7 - The Titration Curve of Histidine The isoelectric pH (pI) is the value at which positive and negative charges are the same. The molecule has no net charge. © 2018 Cengage Learning. All Rights Reserved. Table 3.2- pKa Values of Common Amino Acids In free amino acids, α-carboxyl and, α-amino groups are titratable groups © 2018 Cengage Learning. All Rights Reserved. Isoelectric pH (pI) The pH at which a molecule has no net charge is called the isoelectric pH, or isoelectric point pI. pK a1 + pK a2 pI = 2 pI for glycine falls midway between the pKa values for the carboxyl and amino groups 1 pI = (pK a  COOH  pK a  NH 3+ ) 2 1  (2.34 + 9.60) = 5.97 2 The above equation is used to calculate pI for the nonpolar amino acids + the two acidic amino acids. pI for Asp= 2.09 + 3.86/2 = 2.975 ≈ 3 pI for Glu= 2.19 + 4.25/2 = 3.22 © 2018 Cengage Learning. All Rights Reserved. Example 3.2 - Amino Acid Titrations Given the following amino acids aspartic acid, alanine, arginine, glutamic acid, leucine, and lysine Which of these amino acids has a net charge of +2 at low pH? Which has a net charge of –2 at high pH? © 2018 Cengage Learning. All Rights Reserved. Example 3.2 - Solution How to calculate pI for the basic amino acids? pI for Lys= (8.95 + 10.53)/2 = 9.74 pI for Arg= (9.04 + 12.48)/2 = 10.76 p𝐾a2 + p𝐾a3 pI = 2 What is the pI for His? The numbers to substitute in the equation for the pI are [pKa2 (6.0) +pKa3 (9.17)]/ 2 = 7.58 Arginine and lysine have net charges of +2 at low pH because of their basic side chains Aspartic acid and glutamic acid have net charges of − 2 at high pH because of their carboxylic acid side chains Alanine and leucine do not fall into either category because they do not have titratable side chains © 2018 Cengage Learning. All Rights Reserved. 3-4 Peptide Bond An amide bond between amino acids in a protein. Individual amino acids can be linked by forming covalent bonds Bond is formed between α-carboxyl group of one amino acid and the α-amino group of the next one Water is eliminated in the process, and the linked amino acid residue remain (Fig. 3.8). A bond formed in this way is called a peptide bond. Peptides: Molecules formed by linking two to several dozen amino acids by amide bonds. © 2018 Cengage Learning. All Rights Reserved. Figure 3.8 - Formation of the Peptide Bond © 2018 Cengage Learning. All Rights Reserved. Figure 3.9 - A Small Peptide Showing the Direction of the Peptide Chain (N-Terminal to C-Terminal) Polypeptide chain Backbone of a protein. Formed by linking amino acids by peptide bonds. © 2018 Cengage Learning. All Rights Reserved. Peptide Bond (continued 2) Carbon–nitrogen bond in a peptide bond is usually written as a single bond, with one pair of electrons shared between the two atoms Single bond can be written as a double bond with a shift in the position of pair of electrons Resonance structures: Structural formulas that differ from each other only in the position of electrons Peptide bond can be represented as a resonance hybrid of two structures (Fig. 3.10). Peptide bond has partial double bond character making it stronger than single bonds Rotation around it is restricted © 2018 Cengage Learning. All Rights Reserved. Figure 3.10 - The Resonance Structures of the Peptide Bond Led to a Planar Group © 2018 Cengage Learning. All Rights Reserved. 3-5 Small Peptides with Physiological Activity Oxytocin and Figure 3.11 - Structures of vasopressin have: Oxytocin and Vasopressin Physiological importance as hormones Have cyclic structures Due to the formation of an (-S-S-) disulfide bond. Each contains 9 A.A residues and has an amide group at the C- terminal end. © 2018 Cengage Learning. All Rights Reserved.