Lecture 8

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 integrates concepts from biology, chemistry, and medicine to understand molecular mechanisms underlying cellular function.

• Key Point: Biochemistry examines the structure and function of biomolecules, including proteins, carbohydrates, lipids, and nucleic acids.

• Example: Enzyme-catalyzed reactions in metabolism.

The Four Classes of Biomacromolecules

Biomacromolecules are large molecules essential for life, classified into four main types:

• Proteins: Polymers of amino acids, perform structural, catalytic, transport, and regulatory functions.

• Carbohydrates: Polymers of sugars, provide energy and structural support.

• Lipids: Hydrophobic molecules, form membranes and store energy.

• Nucleic Acids: DNA and RNA, store and transmit genetic information.

Proteins: Structure and Function

Roles of Proteins in the Body

Proteins are versatile biomolecules with diverse functions:

• Enzymes: Catalyze biochemical reactions (biological catalysts).

• Hormones: Regulate physiological processes (e.g., insulin, growth hormone).

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

• Transport Proteins: Move substances across membranes and in blood (e.g., hemoglobin, serum albumin).

• 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 the function of a protein is determined by its shape and the chemical properties of its amino acid residues. Structural knowledge enables prediction of function, understanding of disease mechanisms, and design of drugs.

Amino Acids: Building Blocks of Proteins

General Structure of an Amino Acid

Amino acids are organic molecules with a central (alpha) carbon bonded to four groups:

• Amine group (–NH2): Basic functional group.

• Carboxylic acid group (–COOH): Acidic functional group.

• Side chain (R group): Variable, determines amino acid properties.

• Hydrogen atom: Completes the tetrahedral geometry.

Most amino acids are chiral, meaning the alpha carbon is attached to four different groups, resulting in non-superimposable mirror images (enantiomers).

Chiral Carbon and Isomerism

A chiral carbon is a carbon atom bonded to four distinct groups. This gives rise to stereoisomers:

• Enantiomers: Mirror-image isomers (e.g., L- and D-amino acids).

• Diastereoisomers: Stereoisomers that are not mirror images.

• Constitutional Isomers: Differ in bonding order of atoms.

Proteins in living organisms are composed almost exclusively of L-amino acids.

Classification of Amino Acids

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

• Nonpolar: Hydrophobic, side chains are alkanes or arenes.

• Neutral Polar: Hydrophilic, side chains contain hydroxyl, thiol, or amide groups.

• Acidic: Side chain contains a carboxylic acid group, negatively charged at pH 7.

• Basic: Side chain contains an amine group, positively charged at pH 7.

Zwitterions and pH Dependence

Amino acids exist as zwitterions at physiological pH (~7), carrying both a positive charge (on the amine group) and a negative charge (on the carboxylate group). The net charge of an amino acid depends on the pH of the environment.

• At low pH: Fully protonated, positive charge.

• At neutral pH: Zwitterionic form, both positive and negative charges.

• At high pH: Deprotonated, negative charge.

Protein Structure: Levels and Stabilizing Interactions

Primary Structure

The primary structure of a protein is the sequence of amino acids linked by peptide bonds. It is written from the N-terminus (amino end) to the C-terminus (carboxyl end).

• Peptide bond: Covalent bond formed between the carboxyl group of one amino acid and the amine group of another.

• Convention: Sequence is unique for each protein and determines higher-order structure.

Secondary Structure

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

• Alpha (α)-helix: Right-handed coil stabilized by hydrogen bonds between backbone amide groups four residues apart.

• Beta (β)-sheet: Extended strands connected by hydrogen bonds between backbone amide groups on adjacent strands (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 pack together away from water.

• Hydrogen bonds: Between side chains and backbone atoms.

• Electrostatic (ionic) interactions: Salt bridges between charged side chains.

• Disulfide bonds: Covalent bonds between cysteine residues.

Quaternary Structure

Quaternary structure arises when two or more polypeptide chains assemble into a functional protein complex. Stabilizing forces include hydrophobic interactions, hydrogen bonds, ionic bonds, and interchain disulfide bonds.

Shape-Determining Amino Acids

Glycine, proline, and cysteine are considered shape-determining amino acids:

• Glycine: Small, flexible, often found in turns.

• Proline: Rigid, induces kinks in polypeptide chains.

• Cysteine: Forms disulfide bonds, stabilizing tertiary and quaternary structure.

Summary Table: Amino Acid Classification

Class	Side Chain Type	Charge at pH 7	Hydrophobic/Hydrophilic
Nonpolar	Alkane/Arene	None	Hydrophobic
Neutral Polar	Hydroxyl/Thiol/Amide	None	Hydrophilic
Acidic	Carboxylic Acid	Negative	Hydrophilic
Basic	Amine	Positive	Hydrophilic

Key Equations and Concepts

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

• Zwitterion Structure: $\text{R-CH(NH_3^+)COO^-}$ at pH 7

• Isoelectric Point (pI): The pH at which the net charge of the amino acid is zero.

Additional info:

These notes cover Chapter 18 (Amino Acids and Proteins) and are directly relevant to GOB Chemistry college courses, specifically addressing protein structure, amino acid classification, and biochemical context.