Amino Acids, Peptides, and Proteins
High-Yield Summary
- An alpha-amino acid = amino group + carboxyl group + H + variable R group (side chain), all on the alpha carbon. Amino acids are amphoteric, existing mostly as zwitterions (NH3+ / COO-) at physiological pH ~7.
- The alpha carbon is chiral in nearly every amino acid; glycine (R = H) is the sole achiral exception (bonded to 2 identical H's).
- Eukaryotic amino acids are almost all L-configuration (Fischer projection vs. glyceraldehyde). L/D ≠ R/S (CIP absolute configuration) — most L-amino acids are S, but cysteine is L yet R (sulfur's high atomic number flips CIP priority).
- 21 proteogenic amino acids in eukaryotes: the standard 20 plus selenocysteine, incorporated via UGA stop-codon recoding directed by a SECIS element.
- 5 side-chain categories: nonpolar/nonaromatic, aromatic, polar uncharged, negatively charged (acidic: Asp, Glu), positively charged (basic: Lys, Arg, His).
- Peptide bonds form via condensation (amino group of one attacks carboxyl carbon of another, losing water) — building dipeptides then polypeptides. Hydrolysis reverses this (protein digestion).
L/D vs. R/S Configuration
| System | Basis |
|---|---|
| L/D | Fischer projection vs. glyceraldehyde reference — amino group left = L, right = D |
| R/S | CIP absolute configuration priority rules — independent system; most L-amino acids happen to be S, but cysteine is L yet R (sulfur's high atomic number reorders CIP priority) |
Key Terms & Amino Acid Categories
- Zwitterion
- A molecule carrying both a positive (protonated amino group) and negative (deprotonated carboxylate) charge while net neutral — the dominant form of amino acids at physiological pH.
- Nonpolar, nonaromatic
- Ala, Val, Leu, Ile, Met, Gly, Pro — hydrocarbon-based, generally hydrophobic, often buried in protein interior. Proline's side chain loops back to bond the amino group (rigid, cyclic).
- Aromatic
- Phe, Tyr, Trp — contain aromatic rings. Phe and Trp mostly hydrophobic; Tyr's ring -OH makes it more hydrophilic.
- Polar, uncharged
- Ser, Thr, Asn, Gln, Cys — O/N/S atoms allow H-bonding but no net charge at physiological pH.
- Negatively charged (acidic)
- Asp, Glu — deprotonated carboxyl side chains at physiological pH; highly hydrophilic.
- Positively charged (basic)
- Lys, Arg, His — protonated amino side chains; hydrophilic, often bind negatively charged molecules (DNA, phosphates).
- Selenocysteine
- The 21st proteogenic amino acid; inserted by recoding an in-frame UGA stop codon via a SECIS mRNA element.
Peptide Bond Formation
- 1One amino acid's free amino group (amino/N-terminus) attacks the carbonyl carbon of another's free carboxyl group (carboxy/C-terminus).
- 2Nitrogen forms the new bond to the carbonyl carbon.
- 3A water molecule is eliminated, producing an amide bond — the peptide bond.
- 4Result: a dipeptide (2 amino acids); repeating the pattern builds polypeptides.
Common MCAT Trap
- Don't assume histidine is fully protonated (charged) at physiological pH the way lysine and arginine are — its imidazole pKa (~6) is close to pH 7.4, so it's often mostly unprotonated despite being classified as "basic."
- L/D and R/S are NOT interchangeable systems even though most L-amino acids are S — cysteine is the classic exception (L but R) because sulfur's higher atomic number changes CIP priority order, while its Fischer-projection-based L classification is unaffected.
- Glycine is the ONLY achiral proteogenic amino acid — every other one (including those with seemingly simple side chains) has a chiral alpha carbon.
Quick Recall
Why is glycine the sole achiral proteogenic amino acid?
Why does cysteine have an R configuration despite being an L-amino acid?
How is selenocysteine incorporated into a growing protein?
What is eliminated when two amino acids form a peptide bond, and what is the resulting bond type?