Pharmaceutical Biochemistry PC 1112: Comprehensive Study Notes

Intermolecular and Intramolecular Forces of Attraction

Types and Effects of Molecular Forces

Understanding the forces between and within molecules is fundamental to biochemistry, as these forces dictate molecular interactions, solubility, and biological function.

• Intermolecular forces: Forces between molecules, including hydrogen bonds, van der Waals forces, dipole-dipole interactions, and ionic interactions.

• Intramolecular forces: Forces within a molecule, such as covalent bonds and ionic bonds.

• Applications: These forces influence solubility, polarity, and the behavior of molecules in aqueous solutions.

• Example: Water's high boiling point is due to strong hydrogen bonding between molecules.

Key Concepts:

• Why oil does not float on water: Due to differences in polarity and density.

• Why gases like Cl2 are easily released: Weak intermolecular forces allow for easy phase transition.

Acids and Bases

Titration Curves and Buffer Systems

Acids and bases are central to biochemical reactions, affecting enzyme activity, protein structure, and metabolic pathways.

• Titration curve: A plot showing the pH change as a function of added titrant, used to determine acid/base properties.

• Henderson-Hasselbalch equation: Relates pH, pKa, and the ratio of conjugate base to acid.

$\text{pH} = \text{p}K_a + \log\left(\frac{[A^-]}{[HA]}\right)$

• Buffer: A solution that resists changes in pH upon addition of acid or base.

• Example: Blood maintains pH using the bicarbonate buffer system.

Gibbs Free Energy

Thermodynamics in Biochemistry

Gibbs free energy determines the spontaneity of biochemical reactions and is essential for understanding metabolism and energy transfer.

• Gibbs free energy equation:

$\Delta G = \Delta H - T\Delta S$

• Negative ΔG: Reaction is spontaneous.

• ATP hydrolysis: Provides energy for cellular processes due to a large negative ΔG.

Carbohydrates

Structure and Function

Carbohydrates are essential biomolecules involved in energy storage, structural support, and cell recognition.

• Monosaccharides: Simple sugars (e.g., glucose, fructose).

• Disaccharides: Two monosaccharides linked (e.g., sucrose).

• Polysaccharides: Long chains (e.g., starch, glycogen, cellulose).

• Glycosidic bond: Covalent bond joining carbohydrate molecules.

• Example: Glycogen is the main storage form of glucose in animals.

Lipids

Types and Biological Roles

Lipids are hydrophobic molecules crucial for membrane structure, energy storage, and signaling.

• Fatty acids: Saturated (no double bonds) and unsaturated (one or more double bonds).

• Triglycerides: Main energy storage lipids, composed of glycerol and three fatty acids.

• Phospholipids: Major components of cell membranes, forming bilayers.

• Membrane dynamics: Include membrane rafts and curvature, affecting protein function and signaling.

Enzymes and Enzyme Kinetics

Mechanisms and Regulation

Enzymes are biological catalysts that accelerate chemical reactions. Their kinetics and regulation are central to metabolic control.

• Michaelis-Menten equation: Describes the rate of enzymatic reactions.

$V_0 = \frac{V_{max}[S]}{K_m + [S]}$

• Km (Michaelis constant): Substrate concentration at half-maximal velocity.

• Enzyme inhibition: Competitive, noncompetitive, and uncompetitive inhibition affect enzyme activity differently.

• Allosteric regulation: Enzyme activity modulated by binding of effectors at sites other than the active site.

Proteins

Structure and Function

Proteins are polymers of amino acids with diverse structures and functions, including catalysis, signaling, and structural support.

• Primary structure: Amino acid sequence.

• Secondary structure: Alpha helices and beta sheets stabilized by hydrogen bonds.

• Tertiary structure: 3D folding driven by side chain interactions.

• Quaternary structure: Assembly of multiple polypeptide chains.

• Peptide bond: Covalent bond linking amino acids.

• Denaturation: Loss of structure and function due to environmental changes.

Nucleic Acids

DNA and RNA Structure and Function

Nucleic acids store and transmit genetic information. DNA and RNA differ in structure and function.

• Nucleotides: Building blocks of nucleic acids, composed of a sugar, phosphate, and nitrogenous base.

• Base pairing: A-T (or A-U in RNA), G-C via hydrogen bonds.

• DNA replication: Semi-conservative process ensuring genetic continuity.

• RNA processing: Includes capping, splicing, and polyadenylation.

• Mutations: Silent, missense, and frameshift mutations can affect protein function.

Protein Synthesis

Transcription and Translation

Protein synthesis involves transcription of DNA to mRNA and translation of mRNA to protein, with differences between prokaryotes and eukaryotes.

• Transcription: Synthesis of RNA from DNA template in the nucleus (eukaryotes).

• Translation: Occurs in the ribosome, converting mRNA sequence into a polypeptide chain.

• Post-translational modifications: Chemical changes to proteins after synthesis, affecting function and localization.