Figure 1.2 — NONPOLAR AMINO ACIDS

🧠 Simplest idea

All amino acids have the same basic backbone, but their blue R side chains are different.
These R groups are mainly nonpolar → they avoid water → they prefer the inside of proteins.

🎨 COLOR GUIDE

• 🔴 Red H = removable/dissociable hydrogen
• 🔵 Blue groups = R side chain
• ⚫ Black = common amino-acid backbone
• 🔵 Names = individual amino acids

⭐ Common backbone

Each amino acid has:

NH₃⁺ — Cα — COOH

and one variable:

🔵 R group

That R group decides the amino acid’s properties.

1️⃣ Glycine — R = H

🔵 Side chain = just H

➡️ Smallest amino acid
➡️ Very flexible
➡️ Only standard amino acid with no chiral α-carbon

pK values shown

• pK₁ ≈ 2.3 = α-carboxyl group loses H⁺
• pK₂ ≈ 9.6 = α-amino group loses H⁺

🧠 Glycine = tiny + flexible

2️⃣ Alanine — R = CH₃

One small methyl group.

➡️ Nonpolar
➡️ Hydrophobic

🧠 Alanine = simple CH₃

3️⃣ Valine

R group branches into:

—CH(CH₃)₂

➡️ Nonpolar
➡️ Branched-chain amino acid (BCAA)

🧠 Valine = V-shaped branch

4️⃣ Leucine

R group:

—CH₂—CH(CH₃)₂

➡️ Nonpolar
➡️ BCAA
➡️ Strongly hydrophobic

5️⃣ Isoleucine

Also branched:

—CH(CH₃)—CH₂—CH₃

➡️ Nonpolar
➡️ BCAA

Easy comparison

Valine + Leucine + Isoleucine = branched-chain amino acids

🧠 BCAA = VIL
Valine
Isoleucine
Leucine

6️⃣ Phenylalanine

🔵 Side chain contains a benzene ring.

➡️ Aromatic
➡️ Strongly hydrophobic/nonpolar

🧠 Phenyl = phenyl ring

7️⃣ Tryptophan

Large aromatic ring system with nitrogen.

➡️ Aromatic
➡️ Mostly nonpolar
➡️ Bulky amino acid

🧠 Tryptophan = biggest aromatic side chain here

8️⃣ Methionine

Side chain contains:

Sulfur (S)

But sulfur is in a thioether, so the side chain is still nonpolar.

➡️ Hydrophobic
➡️ Sulfur-containing amino acid

🧠 Methionine = sulfur but nonpolar

9️⃣ Proline — SPECIAL

Its side chain bends back and attaches to the amino nitrogen, making a ring.

➡️ Very rigid
➡️ Limits rotation of the protein backbone
➡️ Often introduces bends/kinks in proteins

🧠 Proline = protein “kink maker”

⭐ Why are these called NONPOLAR?

Their side chains generally:

• do not carry charge
• do not interact strongly with water
• prefer hydrophobic environments

So in a soluble protein:

Nonpolar amino acids → usually hide inside the protein

This helps stabilize protein structure through hydrophobic interactions.

🧠 Fastest exam recall

Nonpolar amino acids shown:

Glycine, Alanine, Valine, Leucine, Isoleucine, Phenylalanine, Tryptophan, Methionine, Proline

Special points:

• Glycine = smallest, achiral
• VIL = branched-chain
• Phenylalanine + Tryptophan = aromatic
• Methionine = sulfur-containing
• Proline = rigid ring, causes bends

⭐ One-line memory

Nonpolar R groups avoid water → cluster inside proteins → stabilize protein by hydrophobic interactions.

Figure 1.3 — POLAR, ACIDIC & BASIC AMINO ACIDS

🧠 Simplest idea

The R side chain decides whether an amino acid is neutral, negative, or positive.

At physiologic pH (~7.4):

• Uncharged polar → mostly 0 charge on R group
• Acidic → negative (−)
• Basic → usually positive (+), except histidine is mostly neutral

🎨 COLOR GUIDE

• 🔴 Red H = hydrogen that can be lost as H⁺
• 🔵 Blue structures = important side-chain groups
• ⚫ Black = common amino-acid backbone
• Arrows to pK values = show how easily a group gives up H⁺

🧠 pK rule

pH > pKa → H⁺ comes OFF
pH < pKa → H⁺ stays ON

1️⃣ TOP — UNCHARGED POLAR SIDE CHAINS

These side chains interact with water but have no major net charge at physiologic pH.

Serine

🔵 R group = –CH₂–OH

The OH makes it polar.

➡️ Can form hydrogen bonds.

Threonine

R group contains:

–OH + CH₃

➡️ Polar because of OH.

Tyrosine

Contains:

Aromatic ring + –OH

The phenolic OH has:

pKa ≈ 10.1

At pH 7.4:

pH < pKa → OH mostly keeps H

➡️ side chain remains uncharged.

Asparagine

Contains an:

Amide group –CONH₂

➡️ Polar
➡️ Uncharged

Glutamine

Also contains:

–CONH₂

Same concept as asparagine, but with an extra CH₂.

➡️ Polar + uncharged

Memory:

Asparagine & Glutamine = amides

Cysteine

Contains:

–SH = sulfhydryl group

Side-chain pKa ≈ 8.3

At pH 7.4, most cysteine remains:

–SH → uncharged

But it can lose H⁺ to become:

–S⁻

⭐ Two cysteines can form a disulfide bond (S–S).

⭐ Uncharged polar memory

S T C N Q Y

Serine
Threonine
Cysteine
AsparagiNe
Glutamine Q
Yrosine

2️⃣ MIDDLE — ACIDIC SIDE CHAINS

Only two:

Aspartic acid

Side chain:

–COOH

pKa ≈ 3.9

At physiologic pH 7.4:

pH > pKa → loses H⁺

So:

–COOH → –COO⁻

➡️ negative charge

Glutamic acid

Also has side-chain:

–COOH

pKa ≈ 4.3

At physiologic pH:

–COOH → –COO⁻

➡️ negative

🧠 Memory:

Acid gives H⁺ away → becomes negative

⭐ Acidic amino acids:

Aspartate (D) + Glutamate (E)

D, E = negatively chargedBOTTOM — BASIC SIDE CHAINS

These contain nitrogen that can accept H⁺.

Histidine

Contains an imidazole ring.

Side-chain pKa ≈ 6.0

At pH 7.4:

pH > pKa

→ much of the side chain has lost H⁺
→ histidine is mostly neutral, but a useful fraction can accept/donate H⁺.

⭐ This makes histidine excellent for enzyme active sites and buffering.

Memory:

Histidine = easy H⁺ exchanger

Lysine

Long side chain ends in:

–NH₃⁺

Side-chain pKa ≈ 10.5

At pH 7.4:

pH < pKa → keeps H⁺

➡️ strongly positive (+)

Arginine

Contains a guanidinium group.

Side-chain pKa ≈ 12.5

At physiologic pH:

➡️ strongly protonated
➡️ strongly positive (+)

Memory:

Arginine holds H⁺ very tightly

⭐ BASIC AMINO ACID MEMORY

H-K-R

Histidine
K = Lysine
R = Arginine

At physiologic pH:

• Lysine → +
• Arginine → +
• Histidine → mostly neutral, but can easily gain/lose H⁺

🔥 Most important physiological-pH concept

At about pH 7.4:

Common backbone

α-COOH → COO⁻
α-NH₂ → NH₃⁺

Side chains

Asp/Glu → COO⁻ → negative

Lys/Arg → protonated → positive

His → mostly unprotonated

🧠 Whole figure in 3 lines

Polar uncharged: Ser, Thr, Tyr, Cys, Asn, Gln → interact with water.

Acidic: Asp, Glu → lose H⁺ → negative.

Basic: His, Lys, Arg → accept H⁺; Lys/Arg are positive at physiologic pH.

⭐ Fastest exam recall

Acidic = D, E = negative
Basic = H, K, R = positive/basic
Polar uncharged = STCNQY

STCNQY is a short memory code for the 6 polar, uncharged amino acids:

• S = Serine
• T = Threonine
• C = Cysteine
• N = Asparagine
• Q = Glutamine
• Y = Tyrosine

These letters are their standard one-letter amino-acid codes. That is why N = Asparagine, Q = Glutamine, and Y = Tyrosine, even though their names do not start with those letters.

🧠 Easy grouping

OH group: Serine, Threonine, Tyrosine
Amide group: Asparagine, Glutamine
SH group: Cysteine

So remember:

STCNQY = Polar + Uncharged at physiologic pH.

Figure 1.4 — Location of Nonpolar Amino Acids in Proteins

🧠 Simplest idea

Nonpolar amino acids avoid water.
So their location depends on where the protein is:

Soluble protein → nonpolar amino acids hide inside
Membrane protein → nonpolar amino acids face outward toward membrane lipids

🎨 COLOR KEY

• 🟡 Yellow circles = nonpolar amino acids
• 🟥 Red squares = polar amino acids
• ⚫ Black/gray chain = protein backbone
• ⚪ Cell membrane = lipid bilayer

1️⃣ LEFT — SOLUBLE PROTEIN

A soluble protein is surrounded by water.

🟡 Nonpolar amino acids

Nonpolar side chains do not like water.

So they:

move away from water → cluster inside the protein

🟥 Polar amino acids

Polar side chains interact well with water.

So they:

face outward → stay on the protein surface

Easy rule:

Water outside
→ polar outside
→ nonpolar inside

🧠 Memory:

Soluble protein = “nonpolar hides.”

2️⃣ RIGHT — MEMBRANE PROTEIN

The middle of the cell membrane contains fatty, hydrophobic lipid tails.

So the situation reverses.

🟡 Nonpolar amino acids

They like the hydrophobic membrane environment.

Therefore:

nonpolar amino acids face outward toward lipid tails

This helps hold the membrane protein inside the membrane.

🟥 Polar amino acids

Where the protein sticks out into watery fluid, polar amino acids can be exposed.

So:

polar residues prefer water-exposed regions⭐ Why the difference?

Soluble protein

Outside environment = water

So:

Nonpolar → inside
Polar → outside

Membrane protein

Outside of the membrane-spanning region = hydrophobic lipid

So:

Nonpolar → surface facing lipids

🧠 Whole figure in one line

Nonpolar amino acids always try to stay away from water:

Soluble protein → hide in the core
Membrane protein → face membrane lipids

🎯 Fastest exam recall

Soluble proteins:
🟡 Nonpolar inside
🟥 Polar outside

Membrane proteins:
🟡 Nonpolar outside toward lipid bilayer

⭐ Memory trick

“Nonpolar follows fat, avoids water.”

Figure 1.5 — Why Proline Is Different

🧠 Simplest idea

Most amino acids have a primary amino group, but proline has a secondary amino group because its side chain loops back and attaches to the amino nitrogen.

1️⃣ LEFT — PROLINE

The side chain of proline contains:

–CH₂–CH₂–CH₂–

and this chain bends back and attaches to the amino nitrogen.

➡️ This creates a 5-membered ring.

🔵 +H₂N = secondary amino group

Why “secondary”?

The nitrogen is attached to two carbon atoms:

• the α-carbon
• a carbon from the R side chain

So proline’s nitrogen is locked into the ring.

Result:

Ring structure → less freedom of rotation → proline is rigid

🧠 Memory:

Proline = Ring = Rigid

2️⃣ RIGHT — ALANINE

Alanine represents the usual amino-acid pattern.

Its amino nitrogen is attached directly to only one carbon, the α-carbon.

🔵 +H₃N = primary amino group

Its R group is simply:

–CH₃

There is no ring connecting back to nitrogen.

➡️ Therefore alanine is much more flexible than proline.

⭐ Main comparison

Proline	Alanine
Secondary amino group	Primary amino group
Nitrogen attached to 2 carbons	Nitrogen attached to 1 carbon
Forms a 5-membered ring	No ring
Rigid	More flexible

🔥 Why is this important in proteins?

Because proline is rigid:

Proline in a polypeptide chain
→ restricts backbone movement
→ often produces a bend/kink

Therefore proline can:

• interrupt α-helices
• help create turns
• contribute to the unusual structure of collagen

🧠 Fastest exam recall

Proline side chain returns to its amino nitrogen → 5-membered ring → secondary amino group → rigid amino acid.

⭐ One-line memory

Proline = secondary amino group + ring + rigidity + helix breaker.