20 Amino Acids
Charge at pH
Resonance
Essential AAs
NONPOLAR (HYDROPHOBIC) — buried in protein interior
POLAR UNCHARGED — H-bond donors/acceptors on protein surface
NEGATIVELY CHARGED (ACIDIC) at pH 7.4
POSITIVELY CHARGED (BASIC) at pH 7.4
*His is ~10% protonated at pH 7.4. Treat as +1 for MCAT unless asked specifically about pH near 6.0.
SPECIAL PROPERTIES TO REMEMBER
Gly = only achiral AA (R = H) · Pro = cyclic, helix breaker · Cys = disulfide bonds (–S–S–) · Trp = largest AA, UV 280nm · Met = start codon (AUG) · Ile, Thr = two chiral centers · Ser, Thr, Tyr = phosphorylation sites · Asn = N-glycosylation (Asn-X-Ser/Thr)
The Rule: If pH < pKa → group is protonated. If pH > pKa → group is deprotonated. Acidic groups (COOH): deprotonation = −1. Basic groups (NH₃⁺): deprotonation = lose +1.
| Group | pKa | Protonated | Deprotonated |
|---|
| α-COOH (C-term) | ~2.0 | –COOH (0) | –COO⁻ (−1) |
| Asp (D) | 3.65 | –COOH (0) | –COO⁻ (−1) |
| Glu (E) | 4.25 | –COOH (0) | –COO⁻ (−1) |
| His (H) | 6.0 | –ImH⁺ (+1) | –Im (0) |
| Cys (C) | 8.18 | –SH (0) | –S⁻ (−1) |
| α-NH₂ (N-term) | ~9.0 | –NH₃⁺ (+1) | –NH₂ (0) |
| Tyr (Y) | 10.07 | –OH (0) | –O⁻ (−1) |
| Lys (K) | 10.53 | –NH₃⁺ (+1) | –NH₂ (0) |
| Arg (R) | 12.48 | guanid⁺ (+1) | guanid (0) |
Worked Example: Ala-Asp-Lys at pH 7.4
α-NH₂: pH 7.4 < 9.0 → protonated → +1
α-COOH: pH 7.4 > 2.0 → deprotonated → −1
Asp: pH 7.4 > 3.65 → deprotonated → −1
Lys: pH 7.4 < 10.53 → protonated → +1
Net: +1 −1 −1 +1 = 0
pI Quick Rules:
Neutral peptide: pI = (pKa α-NH₂ + pKa α-COOH) / 2 ≈ 5.5
Acidic peptide: pI = average of two lowest pKas
Basic peptide: pI = average of two highest pKas
At pH = pI → no migration in electric field
Core Fact: The peptide bond has ~40% double-bond character from resonance. The N lone pair delocalizes into the C=O π system. This makes the bond planar, rigid, and shorter (1.33 Å vs 1.47 Å for a pure C–N).
Nitrogen hybridization: sp² (NOT sp³). The lone pair is in a p orbital participating in resonance, not a tetrahedral lone pair. Geometry = trigonal planar (120°).
Which bonds rotate? Only φ (N–Cα) and ψ (Cα–C'). The peptide bond (C'–N) CANNOT rotate. These two angles determine all secondary structure.
Trans vs Cis: Trans is ~1000:1 favored (R groups on opposite sides = less steric strain). Exception: X-Pro bonds are only ~30:1 trans:cis because Pro's ring minimizes the steric difference.
⚠️ TRAP: "The peptide bond is planar because of hydrogen bonding" — WRONG. H-bonds stabilize secondary structure (α-helices, β-sheets). Planarity comes from resonance. Don't confuse them.
Mnemonic: PVT TIM HALL
Phe · Val · Thr · Trp · Ile · Met · His · Arg* · Leu · Lys
These 10 amino acids cannot be synthesized by humans — they must come from diet.
*Arg is conditionally essential (required during growth, synthesized in adults).
Why can't humans make them? Their carbon skeletons require biosynthetic pathways (like the shikimate pathway for aromatic AAs) that exist in plants, fungi, and bacteria but NOT in animal metabolism. This is why dietary protein quality matters — "complete" proteins contain all essential AAs.
Glucogenic vs Ketogenic:
Purely ketogenic (can only make ketone bodies/acetyl-CoA): Leu, Lys
Both glucogenic & ketogenic: Ile, Phe, Trp, Tyr, Thr
All others: Purely glucogenic (can make glucose)
Branched-Chain AAs (BCAAs): Val, Leu, Ile — all nonpolar, all essential. Metabolized primarily in muscle (not liver). Important in exercise physiology and MSUD (Maple Syrup Urine Disease — deficiency in branched-chain α-keto acid dehydrogenase).