Amino Acid Quiz for the MCAT: Classes, Charges and pKa Questions

The MCAT rarely asks you to draw all 20 amino acids. It asks you to classify them, predict charge at a given pH, and recognize a few special residues. Cover the answers below and try each question.

Quick classes to know

• Nonpolar, aliphatic: glycine, alanine, valine, leucine, isoleucine, methionine, proline.
• Aromatic: phenylalanine, tyrosine, tryptophan.
• Polar, uncharged: serine, threonine, cysteine, asparagine, glutamine (tyrosine is also polar).
• Acidic (negative at pH 7.4): aspartate, glutamate.
• Basic (positive at pH 7.4): lysine, arginine, histidine (histidine is mostly neutral at 7.4, with a side-chain pKa near 6).

Questions

1. Which amino acid is achiral? Glycine. Its side chain is hydrogen, so the alpha carbon has two identical groups.

2. Which amino acid has a ring that includes the backbone nitrogen, and what does it do to a helix? Proline. The ring restricts rotation and breaks alpha helices and beta sheets, which makes it common in turns.

3. Which amino acid forms disulfide bonds? Cysteine, through the oxidation of two thiol side chains into a covalent bond between two cysteines.

4. What is the charge of aspartate at pH 7.4? Net negative. The side-chain carboxyl (pKa near 4) is deprotonated, as is the alpha carboxyl (pKa near 2); the amino group (pKa near 9 to 10) is protonated.

5. Is lysine's side chain protonated at pH 7.4? Yes. Its side-chain amine has a pKa near 10.5, well above 7.4, so it carries a positive charge.

6. Which amino acids can be phosphorylated? Serine, threonine and tyrosine, which have hydroxyl groups.

7. A zwitterion at its isoelectric point (pI): what is the net charge? Zero. For an amino acid with no ionizable side chain, pI is the average of the two backbone pKa values; for acidic or basic residues, average the two pKa values that surround the neutral form.

A pKa rule that answers most charge questions

Compare the pH to the group's pKa. If pH is below pKa, the group is mostly protonated. If pH is above pKa, it is mostly deprotonated. Carboxylic acids are neutral when protonated and negative when deprotonated; amines are positive when protonated and neutral when deprotonated.

Common traps

• Calling histidine positive at 7.4. Its side-chain pKa is near 6, so most molecules are neutral, though the exact fraction depends on the environment.
• Assuming all amino acids are L and S. Natural amino acids are L, but cysteine is R by CIP priorities because sulfur outranks the carboxyl carbon.
• Using the wrong pKa for the side chain. Check the table in the passage.

One-minute recap

• Classify by side chain: nonpolar, aromatic, polar, acidic, basic.
• Use pH versus pKa to assign charge, and average the right two pKa values for pI.
• Glycine is achiral, proline is cyclic, cysteine forms disulfides.