Amino Acids and Peptides Notes

Amino Acids and Peptides

Suggested Readings:

• B-S pp. 29-46

Introduction

• Protein Structure and Function
  • 2.1 Proteins Are Built from a Repertoire of 20 Amino Acids
  • 2.2 Primary Structure: Amino Acids Are Linked by Peptide Bonds to Form Polypeptide Chains
  • 2.3 Secondary Structure: Polypeptide Chains Can Fold Into Regular Structures Such as the Alpha Helix, the Beta Sheet, and Turns and Loops

Study Tips

• There are 20 amino acids used for protein synthesis.
• Familiarize yourself with their names and types of structure (acidic, basic, nonpolar, aromatic).

1. Amino Acids and Peptides

• Amino acids are the basic building blocks of peptides and proteins.
• Larger molecules are formed by linear assembly of specific amino acids into polymers.

2. Asymmetry of Amino Acids

• All amino acids are asymmetrical (chiral) around the alpha carbon (the carbon next to the carboxyl group).
• Asymmetric molecules have L- and D- isomers, which are mirror images of each other.
• All amino acids present in proteins have the L-configuration.

3. Acidic and Basic Properties

• All amino acids have both a weak acidic (carboxyl or –COOH) and weakly basic (-NH2) group.
• The acid group gives up its proton (becomes de-protonated) at a pH above ~2.
• The amino group is weakly basic and becomes protonated (to -NH3+) when the pH is below ~9.0.
• At intermediate pH levels, including neutral pH of 7.0, both of these groups are ionized.
• The net effect is that the amino acid has both a positive charge (from the –NH3+) and a negative charge (from the –COO-).
• Molecules with two opposite charges are called zwitterions.

4. Peptide Bonds

• Peptide bonds form the basic chemical backbone of peptides and proteins.
• They are formed by covalent linkage of the carboxyl group from one amino acid and the amino group from a second amino acid.
• Amide bonds are a more general term for the carboxyl-amino linkage; peptide bond indicates that the functional groups are part of amino acids.

5. Polypeptide Characteristics

• Any specific polypeptide or protein is characterized by:
  • The number of amino acids covalently linked in the chain
  • The specific sequence of these amino acids which are linked in peptide bonds.
• R is used to designate the rest of the amino acid; i.e. the portion of the molecule other than the carboxyl group and the alpha-carbon with its amino group.
• The polypeptide is a zwitterion with the N terminal –NH3+ and the C-terminal –COO- as oppositely charged groups.

6. Side Chains and Unique Properties

• The side chains of the amino acids provide the unique properties of the polypeptide or protein.
• Leu-enkephalin (Tyr-Gly-Gly-Phe-Leu) is an opioid peptide that modulates the perception of pain.
• If the same amino acids were assembled in the reverse sequence (Leu-Phe-Gly-Gly-Tyr), the molecule would not have the same opioid effects.

7. The 20 Amino Acids

• All protein synthesis utilizes a set of 20 amino acids.
• They are alpha amino acids (the –NH3+ group is on the carbon adjacent to the carboxyl carbon) and they all have the L- stereochemical structure.
• Approximately half of the amino acids have nonpolar side chains.
• The other half can be divided into those where the side chain is polar but uncharged, and those that have either positive or negatively charged functional groups on their side chain.
• Amino acid abbreviations:
  • Three-letter abbreviations are fairly straightforward.
  • Molecular biologists often use the one-letter designations.

8. Nonpolar Side Chains

• Glycine: R group is hydrogen.
• Alanine: R is a methyl or –CH3 group.
• Valine, leucine, and isoleucine: longer hydrocarbon groups (branched-chain).

9. Proline, Methionine, and Cysteine

• Proline: a nonpolar amino acid (technically an imino acid) in which the side chain forms a ring structure with the nitrogen on the alpha carbon.
• Methionine and cysteine are the two amino acids that contain sulfur as well as carbon, hydrogen and nitrogen.
• The sulfur of cysteine is present as an –SH (sulfhydryl group) which can react with other –SH groups.
• Methionine has a longer hydrocarbon chain than cysteine. In addition, the sulfur atom is methylated (-S-CH3) rather than simply being a sulfhydryl group.

10. Aromatic Amino Acids

• Phenylalanine, tyrosine, and tryptophan have aromatic rings on their side chains.
  • "Aromatic" refers to the physical and chemical properties of a hydrocarbon ring in which there are alternating single and double bonds
• Phenylalanine and tryptophan are nonpolar and hydrophobic.
• Tyrosine is similar to phenylalanine, but has a hydroxyl (-OH) group on the ring; it is therefore more polar than phenylalanine.
• Tryptophan has a more complex structure with two fused rings; there is a six-member all carbon ring sharing two carbons with a five-member ring that contains a nitrogen atom as well as carbons.
• Five amino acids have side chains that contain groups that are ionized at physiological pH.

11. Charged Amino Acids

• Charged amino acids have an additional charged group on their side chains in addition to the balanced negative (carboxyl; --COO-) and positively (alpha amino, --NH3+) groups of the basic amino acid structure.
• Aspartate and glutamate are acidic amino acids.
  • They have an additional carboxyl group with a negative charge (-COO-) at the end of the side chain.
• Lysine and arginine are basic amino acids.
  • Both have additional nitrogen groups and a net positive charge.
  • The functional group of lysine is a second amino group; that of arginine is more complex, containing three nitrogens covalently bond to the same carbon.

12. Histidine

• Histidine has a ring structure that contains two nitrogen and three carbon atoms.
  • This ring structure does not contain alternating single and double bonds and is therefore not aromatic
• At a pH slightly below 7.0, it accepts an additional hydrogen ion and acquires a positive charge.
• Histidine is often found in the active site of enzymes.
  • Its ability to bind and release protons contributes to the mechanism of catalysis.

13. Polar, Un-ionized Amino Acids

• Serine and threonine contain hydroxyl groups.
  • Tyrosine can also be included here; it is both an aromatic and a polar, hydroxyl-containing amino acid.
• Asparagine and glutamine are derived from aspartate and glutamate, respectively.
  • In both cases, there is an NH3 group (ammonia) in amide linkage on the side- chain carboxyl group.
  • The result is a highly polar (hydrophilic) side chain, but one that can no longer ionize at physiological pH.

14. Leu-enkephalin Revisited

• Leu-enkephalin contains two large, aromatic side chains (phenylalanine and tyrosine), one branched-chain amino acid (leucine) and two small, non-polar glycines.

15. Cysteine and Disulfide Bridges

• The sulfhydryl group of cysteine plays a major role in stabilizing protein structure, particularly in extracellular and secreted proteins.
• Oxidation of two sulfhydryl groups results in the formation of a disulfide bridge (-S-S-) linking two cysteine side-chains.
• The reaction (2 –SH _rightarrow -S-S-) is an oxidation in that there is removal of two hydrogen atoms from the molecule.
  • This is alternatively described as removal of two electrons and the accompanying protons or hydrogen ions.
• Oxidative processes that remove hydrogen atoms (and do not directly involve molecular oxygen) will be seen throughout the study of metabolism.

16. Vasopressin

• Vasopressin is a small peptide hormone that stimulates the kidney to reabsorb water.
• It contains nine amino acids with a disulfide bridge between the two cysteine residues.
• The molecule has a net charge of zero, with one positively charged side chain (Arg) and one negatively charged side chain (Glu).
• A synthetic peptide analog is used as a drug for people who do not synthesize sufficient hormone.

17. Insulin

• The hormone insulin is secreted by beta cells of the pancreas and serves to regulate levels of sugar in the blood.
• It has two peptide chains of 21 and 30 amino acids, respectively, with different amino acid sequences.
• The two chains are attached to each other by the covalent bonds of two disulfide bridges.
• There is also a disulfide bridge which forms a loop within the A chain.