Question

How does the pKa values of an ionizable side chain compare when the amino acid is free versus when it is in a polypeptide chain? The pKa of the side chain is always lower for the free amino acid. The pKa of the side chain is usually higher in a polypeptide chain due to stabilization from nearby residues in the three-dimensional structure. The pKa of the side chain is independent of whether the amino acid is in a polypeptide chain or is free. The pKa of the side chain may be lower or higher in a polypeptide chain due to weaker inductive effects and differences in their microenvironments.

Answer 1

The
`\( pK_a \)` of the side chain may be lower or higher in a polypeptide chain due to differences in their microenvironments.

Step-by-step explanation:

The
`\( pK_a \)` values of ionizable side chains can vary depending on whether the amino acid is free or is part of a polypeptide chain. This variation is primarily due to the microenvironment in which the side chain finds itself when it's part of a larger protein structure.

In a polypeptide chain, the side chain's
`\( pK_a \)` can be influenced by several factors:

1. Proximity to other charged residues which can either stabilize or destabilize the ionized form of the side chain.

2. The hydrophobic or hydrophilic environment in which the side chain resides, which can affect its tendency to gain or lose a proton.

3. Hydrogen bonding with neighboring residues.

4. The overall three-dimensional structure of the protein, which might position the side chain in a more exposed (to the solvent) or more buried position.

Given these considerations, the correct statement is:

The
`\( pK_a \)` of the side chain may be lower or higher in a polypeptide chain due to differences in their microenvironments.