4-hydroxy-2-nonenal (4HNE), shown below, interacts with proteins by forming covalent bonds with the nucleophilic side chains of amino acids. If a protein were incubated with 4HNE and then degraded by proteases, which of the following could represent the structure and charge of an amino acid bound to 4HNE at pH 7?

Question

4-hydroxy-2-nonenal (4HNE), shown below, interacts with proteins by forming covalent bonds with the nucleophilic side chains of amino acids.  If a protein were incubated with 4HNE and then degraded by proteases, which of the following could represent the structure and charge of an amino acid bound to 4HNE at pH 7?

Quizplus · Accepted Answer

11ecba2d_0e99_d5d2_a3bf_1112915030b8_MD0008_00 All amino acids contain a carboxyl group and an amino group in their backbones that can be protonated or deprotonated, depending on the pH to which they are exposed. The carboxyl group has a pKa of approximately 2 and typically acts as a proton donor; the amino group has a pKa of about 9 and generally acts as a proton acceptor. At or near physiological pH (7.4), amino acid backbones exist as zwitterions, molecules that have both a positive and a negative charge, which cancel each other; the carboxyl group is deprotonated (COO⁻) and carries a negative charge while the amino group is fully protonated (NH₃⁺) and has a positive charge. According to the question, 4HNE forms covalent bonds with nucleophilic amino acids, which contain side chains with atoms that can donate electrons when they are deprotonated. The question further states that this process occurs in at pH 7. This pH is higher than the pKa of the carboxyl group, but lower than the pKa of the amino group; therefore, the amino acid would exist predominantly as a zwitterion. Of the available choices, cysteine is the only nucleophilic amino acid displayed as a zwitterion. (Choices A and D) Nonpolar amino acids such as tryptophan and proline do not contain nucleophilic side chains. The backbone amino group would be protonated at pH 7 in tryptophan and proline. The backbone carboxyl group would be deprotonated at pH 7 in proline. (Choice C) Serine is a nucleophilic amino acid, but the backbone carboxyl group would be deprotonated and negatively charged at pH 7. Educational objective: At or near physiological pH (7.4), amino acid backbones predominantly exist as neutral molecules referred to as zwitterions. They have a net charge of zero because the carboxyl group (pKa of 2) is deprotonated (COO⁻) while the amino group (pKa of 9) is protonated (NH₃⁺). Nucleophillic amino acids contain side chains with atoms that donate electrons when they are deprotonated.

4-Hydroxy-2-Nonenal (4HNE), Shown Below, Interacts with Proteins by Forming Covalent