Proteins and Their Amino Acid Building Blocks: Structure and Function

Biochemistry and Biomacromolecules

What is Biochemistry?

Biochemistry is the study of the chemistry of life, focusing on the chemical reactions and processes that occur within living organisms. It bridges biology and chemistry, encompassing fields such as cell biology, physiology, pharmacology, and more.

• Key Point: Biochemistry investigates the molecular mechanisms underlying biological functions.

• Key Point: It is foundational for understanding medicine, neurology, immunology, and related sciences.

The Four Classes of Biomacromolecules

Living organisms are composed of four major classes of biomacromolecules, each with distinct structures and functions:

• Proteins: Polymers of amino acids, responsible for catalysis, structure, transport, and regulation.

• Lipids: Hydrophobic molecules, key components of membranes and energy storage.

• Carbohydrates: Sugars and polysaccharides, providing energy and structural support.

• Nucleic Acids: DNA and RNA, carriers of genetic information.

Proteins: Structure and Function

Roles of Proteins in the Body

Proteins are essential macromolecules with diverse roles:

• Enzymes: Biological catalysts that accelerate chemical reactions (e.g., hexokinase).

• Hormones: Chemical messengers regulating physiological processes (e.g., insulin, glucagon).

• Storage Proteins: Store essential substances (e.g., ferritin stores iron).

• Transport Proteins: Move molecules across membranes or in blood (e.g., hemoglobin, glucose transporter).

• Structural Proteins: Provide support and shape (e.g., collagen, keratin).

• Protective Proteins: Defend against pathogens (e.g., antibodies).

• Contractile Proteins: Enable movement (e.g., actin, myosin).

Importance of Protein Structure

Understanding protein structure is crucial because a protein's function is determined by its three-dimensional shape, which is dictated by its amino acid sequence and the interactions among its residues.

• Key Point: Structural changes (mutations, denaturation) can lead to loss of function or disease.

Amino Acids: Building Blocks of Proteins

General Structure of an Amino Acid

All amino acids share a common structure:

• Central alpha carbon (Cα)

• Amino group (–NH2)

• Carboxylic acid group (–COOH)

• Hydrogen atom

• Side chain (R group): unique for each amino acid

Amino acids are chiral (except glycine), meaning the alpha carbon is bonded to four different groups, resulting in non-superimposable mirror images (enantiomers).

Chirality and Isomerism

• Chiral Carbon: A carbon atom bonded to four different groups.

• Isomers: Compounds with the same formula but different structures.

• Constitutional Isomers: Differ in bonding order of atoms.

• Stereoisomers: Same bonding order, different spatial arrangement.

• Enantiomers: Non-superimposable mirror images.

• Diastereoisomers: Stereoisomers that are not mirror images.

Classification of Amino Acids

Amino acids are classified based on the properties of their side chains:

Class	Side Chain Properties	Example
Nonpolar	Alkanes, arenes (hydrophobic)	Leucine
Neutral Polar	Hydroxyl, thiol, amide (hydrophilic)	Serine
Acidic	Carboxylic acid (negative charge at pH 7)	Aspartic acid
Basic	Amine (positive charge at pH 7)	Lysine

Zwitterions and pH Dependence

At physiological pH (~7), amino acids exist as zwitterions, carrying both a positive charge (on the amino group) and a negative charge (on the carboxyl group):

• At low pH: fully protonated, net positive charge

• At neutral pH: zwitterionic, net zero charge

• At high pH: deprotonated, net negative charge

The isoelectric point (pI) is the pH at which the amino acid has no net charge.

Protein Structure: Levels of Organization

Primary Structure

The primary structure is the linear sequence of amino acids in a protein, linked by peptide bonds (amide bonds). Proteins are written from the N-terminus (amino end) to the C-terminus (carboxyl end).

• Key Point: The sequence determines all higher levels of structure and function.

Secondary Structure

Secondary structure refers to local folding patterns stabilized by hydrogen bonds between backbone atoms:

• α-Helix: Right-handed coil stabilized by hydrogen bonds every fourth residue.

• β-Sheet: Extended strands connected by hydrogen bonds, can be parallel or antiparallel.

Tertiary Structure

Tertiary structure is the overall three-dimensional shape of a single polypeptide chain, stabilized by:

• Hydrophobic interactions (nonpolar side chains cluster inside)

• Hydrogen bonds (between side chains or backbone)

• Disulfide bonds (covalent bonds between cysteine residues)

• Electrostatic (ionic) interactions (between charged side chains)

• Van der Waals forces

Quaternary Structure

Quaternary structure arises when two or more polypeptide chains (subunits) assemble into a functional protein complex. Stabilized by the same interactions as tertiary structure, plus interchain disulfide bonds in some cases.

Shape-Determining Amino Acids

• Glycine: Smallest side chain (H), provides flexibility, often found in turns.

• Proline: Rigid ring structure, introduces kinks, found at ends of helices and in turns.

• Cysteine: Contains thiol group, forms disulfide bonds that stabilize structure.

Stabilizing Interactions by Structure Level

Structure Level	Stabilizing Interactions
Primary	Covalent peptide bonds
Secondary	Hydrogen bonds (backbone)
Tertiary	Hydrophobic effect, hydrogen bonds, ionic bonds, disulfide bonds, van der Waals
Quaternary	Hydrophobic effect, hydrogen bonds, ionic bonds, disulfide bonds (between chains)

Summary Table: Amino Acid Classification

Class	Side Chain Property	Hydrophobic/Hydrophilic	Example
Nonpolar	Alkyl/aromatic	Hydrophobic	Valine
Neutral Polar	OH, SH, amide	Hydrophilic	Serine
Acidic	COOH	Hydrophilic	Aspartic acid
Basic	NH2	Hydrophilic	Lysine

Key Equations

• Peptide Bond Formation: $\mathrm{Amino\ acid}_1 + \mathrm{Amino\ acid}_2 \rightarrow \mathrm{Dipeptide} + \mathrm{H}_2\mathrm{O}$

• Zwitterion Formation (at pH 7): $\mathrm{H}_3\mathrm{N}^+-\mathrm{CHR}-\mathrm{COO}^-$

Additional info: This guide covers the foundational aspects of protein structure and function, including amino acid chemistry, protein folding, and the importance of side chain properties in biological systems. For further reading, consult Chapter 18, sections 18.1-18.6 in your textbook.