MCAT Biochemistry Review

Chapter 1: Amino Acids, Peptides, and Proteins

1.3 Peptide Bond Formation and Hydrolysis

Peptides are composed of amino acid subunits, sometimes called residues, shown in Figure 1.9. Dipeptides consist of two amino acid residues; tripeptides have three. The term oligopeptide is used for relatively small peptides, up to about 20 residues; while longer chains are calledpolypeptides.

Figure 1.9. Peptide Residues

BRIDGE

For Test Day, you also need to know how peptide bonds are formed in the context of ribosomes, which is covered in Chapter 7 of MCAT Biochemistry Review.

The residues in peptides are joined together through peptide bonds, a specialized form of an amide bond, that forms between the –COO group of one amino acid and the NH3+ group of another amino acid. This forms the functional group –C(O)NH–. In this section, we'll look at the key reactions involved in forming and breaking peptide bonds.

PEPTIDE BOND FORMATION

Peptide bond formation is an example of a condensation or dehydration reaction because it results in the removal of a water molecule (H2O); it can also be viewed as an acyl substitution, which can occur with all carboxylic acid derivatives. When a peptide bond forms, as shown in Figure 1.10, the electrophilic carbonyl carbon on the first amino acid is attacked by the nucleophilic amino group on the second amino acid. After that attack, the hydroxyl group of the carboxylic acid is kicked off. The result is the formation of a peptide (amide) bond.

Figure 1.10. Peptide Bond Formation and Cleavage

Because amide groups have delocalizable π electrons in the carbonyl and in the lone pair on the amino nitrogen, they can exhibit resonance; thus, the C–N bond in the amide has partial double bond character, as shown in Figure 1.11.

Figure 1.11. Resonance in the Peptide Bond

As a result, rotation of the protein backbone around its C–N amide bonds is restricted, which makes the protein more rigid. Rotation around the remaining bonds in the backbone, however, is not restricted, as those remain single (σ) bonds.

When a peptide bond forms, the free amino end is known as the amino terminus or N-terminus, while the free carboxyl end is the carboxy terminus or C-terminus. By convention, peptides are drawn with the N-terminus on the left and the C-terminus end on the right; similarly, they are read from N-terminus to C-terminus.

BRIDGE

The peptide is drawn in the same order that it is synthesized by ribosomes: from the N-terminus to the C-terminus! Translation is covered in Chapter 7 of MCAT Biochemistry Review.

PEPTIDE BOND HYDROLYSIS

For enzymes to carry out their function, peptides need to be relatively stable in solution. Therefore, they don't normally fall apart on their own. On the other hand, in order to digest proteins, we need to break them down into their component amino acids. In organic chemistry, amides can be hydrolyzed using acid or base catalysis.

In living organisms, however, hydrolysis is catalyzed by hydrolytic enzymes such as trypsin and chymotrypsin. Both are specific, in that they only cleave at specific points in the peptide chain: trypsin cleaves at the carboxyl end of arginine and lysine, while chymotrypsin cleaves at the carboxyl end of phenylalanine, tryptophan, and tyrosine. While you don't need to know the exact mechanism of how these enzymes catalyze hydrolysis, you do need to understand the main idea: they break apart the amide bond by adding a hydrogen atom to the amide nitrogen and an OH group to the carbonyl carbon. This is the reverse reaction shown before in Figure 1.10.

MCAT EXPERTISE

You do not need to memorize the specific amino acids that hydrolytic enzymes recognize or the exact mechanisms for those reactions. On the other hand, you could certainly encounter a passage describing them.

MCAT Concept Check 1.3:

Before you move on, assess your understanding of the material with these questions.

1.    What is the difference between an amino acid, a dipeptide, a tripeptide, an oligopeptide, and a polypeptide?

2.    What molecule is released during formation of a peptide bond?

3.    If chymotrypsin cleaves at the carboxyl end of phenylalanine, tryptophan, and tyrosine, how many oligopeptides would be formed in enzymatic cleavage of the following molecule with chymotrypsin?

Val – Phe – Glu – Lys – Tyr – Phe – Trp – Ile – Met – Tyr – Gly – Ala