All amino acids have the same basic structure with four groups attached to a central alpha (α) carbon atom:

🌊 Amphiprotic Nature of Amino Acids

Amino acids are amphiprotic (or amphoteric) molecules—they can act as both acids and bases:

• The carboxyl group (–COOH) can donate a proton → acts as an acid
• The amino group (–NH₂) can accept a proton → acts as a base
• In solution, amino acids exist as zwitterions—molecules with both positive and negative charges: NH₃⁺–CH(R)–COO^-

The R-group (side chain) is the variable portion of an amino acid that determines its chemical properties and behavior. R-groups differ in:

Classification of Amino Acids by R-Group Properties

What is a Peptide Bond?

A peptide bond is a covalent bond formed between the carboxyl group (–COOH) of one amino acid and the amino group (–NH₂) of another amino acid.

The peptide bond is also called an amide bond or peptide linkage.

Formation Process: Condensation (Dehydration Synthesis)

Properties of Peptide Bonds

• Strong covalent bond: Not easily broken by heat or salt, but can be hydrolyzed by strong acids/bases or enzymes (proteases)
• Partial double bond character: Resonance between C–N single bond and C=N double bond makes the bond rigid
• Planar (flat) structure: The six atoms in the peptide bond (C–C–N–C–C–O) lie in the same plane
• Restricts rotation: Rigidity limits the conformations a polypeptide can adopt, influencing protein structure
• Polar nature: The C=O and N–H groups can form hydrogen bonds, crucial for protein folding

🔑 Key Point:

In cells, peptide bond formation requires energy (ATP) and occurs in ribosomes during translation. The process is catalyzed by ribosomal RNA (rRNA), making protein synthesis a fundamental cellular process.

Polypeptide Chain Features

• Directionality: Polypeptides have two distinct ends:
  • N-terminus: Free amino group (–NH₂) at one end
  • C-terminus: Free carboxyl group (–COOH) at the other end
• Read from N→C: Polypeptide sequences are conventionally written from N-terminus to C-terminus (left to right)
• Backbone: The repeating –N–C–C– pattern forms the polypeptide backbone
• Side chains: R-groups of amino acids project from the backbone and determine protein properties

Peptide bonds can be broken through hydrolysis—the reverse of condensation. A water molecule is used to break the C–N bond:

• Digestion: Protease enzymes (pepsin, trypsin, chymotrypsin) break down dietary proteins into amino acids
• Protein turnover: Cells continuously break down and rebuild proteins
• Regulation: Controlled hydrolysis activates or deactivates certain proteins

💡 Mnemonic to Remember:

PVT TIM HALL

Phenylalanine, Valine, Threonine, Tryptophan, Isoleucine, Methionine, Histidine, Arginine*, Leucine, Lysine

*Arginine is conditionally essential (essential for children and during illness)

Complete Proteins (Contain All 9 Essential Amino Acids)

• Animal sources: Meat, poultry, fish, eggs, dairy products (milk, cheese, yogurt)
• Plant sources: Quinoa, soy products (tofu, tempeh, edamame), buckwheat, hemp seeds, chia seeds

Incomplete Proteins (Missing One or More Essential Amino Acids)

Most plant foods: beans, lentils, nuts, seeds, grains. Can be combined to provide all essential amino acids:

• Rice + Beans: Complementary proteins providing all essential amino acids
• Peanut butter + Whole wheat bread: Complete protein combination
• Hummus + Pita bread: Chickpeas complement grains

Non-Essential Amino Acids (11 types)

The body can synthesize these from other compounds, so they don't need to be in the diet:

Alanine, Arginine*, Asparagine, Aspartic acid, Cysteine*, Glutamic acid, Glutamine*, Glycine*, Proline*, Serine, Tyrosine*

Conditionally Essential Amino Acids (*marked above)

Become essential during specific physiological conditions (infancy, illness, pregnancy, stress) when the body cannot produce sufficient amounts. Examples: Arginine (essential for children), Glutamine (during illness), Cysteine (for premature infants).

Definition

The primary structure is the linear sequence of amino acids in a polypeptide chain, from the N-terminus to the C-terminus.

This is essentially a "list" of which amino acids appear in what order, connected by peptide bonds.

Key Features:

• Held together by peptide bonds (covalent bonds)
• Determined by the gene sequence (DNA)
• Unique to each protein
• Even a single amino acid change can dramatically affect protein function
• Written conventionally from N-terminus → C-terminus (left to right)

🔍 Example: Sickle Cell Anemia

A single amino acid substitution in hemoglobin causes sickle cell disease:

• Normal hemoglobin: ...Valine-Histidine-Glutamic acid-Threonine...
• Sickle cell hemoglobin: ...Valine-Histidine-Valine-Threonine...

This one change causes red blood cells to become sickle-shaped, reducing oxygen transport capacity.

Definition

The secondary structure is the regular, repeating folding patterns of the polypeptide backbone into specific structures, stabilized by hydrogen bonds.

Two Main Types:

🔑 Key Point:

Secondary structure hydrogen bonds form between the backbone atoms (C=O and N-H), not between R-groups. The R-groups are not involved in stabilizing secondary structure.

Definition

The tertiary structure is the complete three-dimensional shape of a single polypeptide chain, formed by interactions between R-groups (side chains) of amino acids that may be far apart in the primary sequence.

This is the functional form of a protein—the shape that allows it to carry out its biological role.

Interactions That Stabilize Tertiary Structure:

🌐 Globular vs. Fibrous Proteins:

• Globular proteins: Compact, spherical tertiary structure (e.g., enzymes, antibodies, hemoglobin). Soluble in water.
• Fibrous proteins: Extended, elongated tertiary structure (e.g., collagen, keratin). Structural roles, often insoluble.

Definition

The quaternary structure is the arrangement and interaction of multiple polypeptide chains (subunits) that assemble to form a functional protein complex.

Not all proteins have quaternary structure—only those composed of two or more polypeptide chains.

Key Features:

• Each polypeptide chain (subunit) has its own primary, secondary, and tertiary structure
• Subunits are held together by the same interactions as tertiary structure (hydrogen bonds, ionic bonds, hydrophobic interactions)
• Subunits may be identical (homooligomer) or different (heterooligomer)
• Often provides stability and allows for regulation of protein activity

🔍 Examples:

1. Temperature (Heat)

2. pH Changes (Acidity/Alkalinity)

3. Other Denaturing Agents

🔑 Key Point:

Denaturation demonstrates the critical importance of three-dimensional structure for protein function. While the amino acid sequence (primary structure) remains unchanged, loss of higher-order structure means loss of function—proving that structure determines function.

✓ Amino Acid Structure

All 20 amino acids share a central carbon with amino group (–NH₂), carboxyl group (–COOH), hydrogen, and variable R-group. The R-group determines each amino acid's unique properties.

✓ Peptide Bonds

Formed by condensation reactions between amino acids, releasing water. Creates strong covalent C–N bonds (amide bonds) that link amino acids into polypeptide chains.

✓ Essential Amino Acids

Nine amino acids humans cannot synthesize (PVT TIM HALL: Phe, Val, Thr, Trp, Ile, Met, His, Leu, Lys). Must be obtained from dietary proteins.

✓ Protein Structure Hierarchy

Primary (sequence) → Secondary (α-helix, β-sheet) → Tertiary (3D shape) → Quaternary (multiple chains). Each level depends on and builds from the previous one.

✓ Denaturation

Loss of protein 3D structure due to heat, pH changes, or chemicals. Disrupts weak bonds (H-bonds, ionic, hydrophobic), causing unfolding and loss of function. Often irreversible.

✓ Structure-Function Relationship

A protein's specific 3D shape determines its function. Even small changes in structure (one amino acid substitution or denaturation) can dramatically alter or eliminate its biological function.