After Chapter 10.1, you will be able to:
Amino acids are dipolar molecules that come together through a condensation reaction, forming peptides. Larger, folded peptide chains are considered proteins.
Amino acids contain an amino group and a carboxyl group attached to a single carbon atom (the α-carbon). The other two substituents of the α-carbon are a hydrogen atom and a side chain referred to as the R group. This structure is shown in Figure 10.1.
The α-carbon, with its four different groups, is a chiral (stereogenic) center. Glycine, the simplest amino acid, is an exception to this rule because its R group is a hydrogen atom. All naturally occurring amino acids in eukaryotes—except for glycine—are optically active, and all are L-isomers. Therefore, by convention, the Fischer projection for an amino acid is drawn with the amino group on the left, as shown in Figure 10.2. L-amino acids have (S) configurations, except for cysteine, which is (R) because of the change in priority caused by the sulfur in its R group.
Amino acids, with their acidic carboxyl group and basic amino group, are amphoteric molecules. That is, they can act as both acids and bases. Amino groups can take on a positive charge by being protonated, and carboxyl groups can take on negative charges by being deprotonated. When an amino acid is put into solution, it will take on both of these charges, forming a dipolar ion or zwitterion, as shown in Figure 10.3. How an amino acid acts depends on the pH of the environment. In basic solutions, the amino acid can become fully deprotonated; in acidic solutions, it can become fully protonated.
Amino acids are amphoteric molecules, just like water—they can act as both acids and bases. These acid–base characteristics (and titrations of amino acids) are discussed thoroughly in Chapter 1 of MCAT Biochemistry Review.
Aside from the zwitterionic properties common to every amino acid, each one has properties defined by its R group, or side chain. The 20 eukaryotic proteogenic amino acids are grouped into five categories: nonpolar nonaromatic, aromatic, polar, negatively charged (acidic), and positively charged (basic). Nonpolar nonaromatic amino acids tend to have side chains that are saturated hydrocarbons, like alanine, valine, leucine, and isoleucine; they also include glycine, proline (which is cyclic, with a secondary amine), and methionine (which contains sulfur). Aromatic amino acids include tryptophan, phenylalanine, and tyrosine. Nonpolar amino acids—both nonaromatic and aromatic—are also hydrophobic and tend to be sequestered in the interior of proteins. Polar amino acids tend to have terminal groups containing oxygen, nitrogen, or sulfur. These include serine, threonine, asparagine, glutamine, and cysteine. Negatively charged (acidic) amino acids include aspartic acid and glutamic acid. These amino acids have terminal carboxylate anions in their R groups. Finally, positively charged (basic) amino acids, including arginine, lysine, and histidine, have a protonated amino group in their R groups. Polar, acidic, and basic amino acids are all hydrophilic and tend to form hydrogen bonds with water in aqueous solution.
Amino acids undergo condensation reactions to form peptide bonds. The molecules these bonds form, called polypeptides, are the base unit of proteins. The reverse reaction, hydrolysis of the peptide bond, is catalyzed by a strong acid or base. Both of these reactions are shown in Figure 10.4.
Like other carbonyl-containing functional groups, amides have two resonance structures, as shown in Figure 10.5. The true structure of the amide bond is therefore a hybrid of these two structures, with partial double-bond character between the nitrogen atom and the carbonyl carbon. This double-bond character limits rotation about the C–N bond, which adds to the rigidity and stability of the backbone of proteins. The single bonds on either side of the peptide bond, on the other hand, permit free rotation.
Rotation is limited around the peptide bond because resonance gives the C–N bond partial double-bond character.