PGY 2320 Medical Biochemistry Quiz

Course Information

• Course: PGY 2320 (Medical Biochemistry & Genetics)
• Year: 2023/2024
• Instructor: Dr. Lubinda Mukololo
• Email: [email protected]
• Department: Physiological Sciences
• School: Medicine
• University: The University of Zambia

Biophysical Chemistry Objectives

• Properties of water as a solvent for biochemical reactions
• Hydrogen bonding
• Weak acids and bases
• pH and pKa determination
• Buffers and their role in biological systems
• Physiologically important buffer systems

Water's Importance in Living Systems

• Solvent/medium for reactions
• Principal reactant in biological processes (e.g., photosynthesis) and final product in aerobic energy metabolism
• Determines the shape of biomolecules due to aqueous environments
• Stabilizes temperature and pH of living organisms

Properties of Water (1. Polarity)

• Covalent bonds between oxygen and hydrogen atoms (bond angle of 104.5°)
• Oxygen is more electronegative than hydrogen, resulting in a polar covalent bond
• Creates a permanent dipole in the water molecule
• Determines relative solubility of molecules ("like dissolves like")

Properties of Water (2. Hydrogen Bonds)

• Polar covalent bonds lead to attraction between water molecules
• Hydrogen bonds form between slightly positive hydrogen atom of one water molecule and slightly negative oxygen atom of another water molecule
• Each water molecule can form hydrogen bonds with four other water molecules
• Hydrogen bond length is approximately twice that of a covalent bond
• Weaker than covalent bonds (about 25x weaker)

Properties of Water (3. Hydrogen Bonds and Melting/Freezing/Density)

• Hydrogen bonds give water a high melting point
• Water expands as it freezes, decreasing its density
• Ice results from an open lattice structure of water molecules
• Ice is less dense but more ordered than liquid water

Properties of Water (4. High Specific Heat and Heat of Vaporization)

• Hydrogen bonds contribute to water's high specific heat
• Hydrogen bonds must be broken to increase kinetic energy and temperature
• Water has a high heat of vaporization due to the need to break hydrogen bonds to change water from liquid to gaseous state

Water as a Universal Solvent

• Water interacts with and dissolves polar compounds and ionized compounds (electrolytes) due to hydrophilicity
• Water molecules align around electrolytes creating solvation spheres
• Solubility of organic molecules in water depends on polarity and ability to form hydrogen bonds with water

Functional groups that confer solubility in water

• carboxylates
• protonated amines
• amino
• hydroxyl groups
• carbonyl groups
• The number of polar groups in a molecule increases its solubility in water

Hydrophobic Interactions

• Nonpolar molecules are not soluble in water
• Water molecules prefer to interact with each other rather than nonpolar molecules, excluding them
• Nonpolar molecules associate with each other due to the hydrophobic effect
• Hydrophobic interactions result from the organization of water molecules around non-polar molecules

Amphipathic Molecules (e.g., detergents or surfactants)

• Have both hydrophilic and hydrophobic portions
• Typically have a hydrophobic chain of 12 carbon atoms plus an ionic or polar end
• Soaps are alkali metal salts of long-chain fatty acids
• Examples of detergents: sodium palmitate, sodium dodecyl sulfate

Micelles

• Spheres formed by amphipathic molecules with hydrophilic heads facing outward and hydrophobic tails facing inward
• Used to trap grease and oils

Noncovalent Interactions in Biomolecules

• Hydrogen bonds: important in stabilizing structures (proteins, nucleic acids) when they occur between molecules
• Hydrophobic interactions: very weak intermolecular forces, important for protein shape and membrane structure
• Charge-charge interactions (ionic bonds): strongest non-covalent force over longer distances, weaken due to water molecules
• Van der Waals forces: weak attractions or repulsions determined by distance

Nucleophilic Nature of Water

• Electron-rich (nucleophiles) attract electron-deficient (electrophiles)
• Negatively charged or with unshared electrons, nucleophiles attack electrophiles during substitution or addition reactions
• Examples of nucleophiles: oxygen, nitrogen, sulfur, carbon, and water (weak)

Condensation and Hydrolysis Reactions

• Important in condensation reactions, where hydrolysis reactions are favored.
• Condensation reactions usually use ATP and exclude water to make reactions more favorable
• Intracellular reactions in the presence of hydrolases

Ionization of Water

• Pure water ionizes slightly, forming hydrogen ions (protons) and hydroxide ions
• Can act as an acid (proton donor) or base (proton acceptor)
• Hydrogen ions formed immediately become hydrated to hydronium ions
• Actual probability of a hydrogen atom being an hydrogen ion is approximately 1.8 * 10-9

Equilibrium Constant for Water

• Keq = [H+][OH-]/[H₂O] = 1.8 x 10-16M at 25°C
• In pure water at 25°C, concentration of water is 55.5 M

pH (Definition and Calculations)

• pH measures the concentration of H+ in a solution
• pH = -log [H+]
• pH < 7 is acidic, pH > 7 is basic (or alkaline)
• One change in pH = 10 fold change in [H+]
• pKa = -log Ka
• pKw =pH + pOH = 14

Weak Acids and Bases

• Ionize slightly in water
• Have characteristic dissociation constants
• Common in biological systems; important for metabolism and regulation
• Acids are proton donors, bases are proton acceptors

Conjugate Acid-Base Pairs

• A proton donor and its corresponding proton acceptor make up a conjugate acid-base pair

pKa (definition)

• pKa of an acid is the pH at which the acid is half dissociated; [A-] = [HA]

Henderson-Hasselbalch Equation

• Describes the dissociation of a weak acid in the presence of its conjugate base
• Important in calculating pH with known concentrations and pKa values

Buffers

• Resist changes in pH
• Consist of a weak acid and its conjugate base or weak base and its conjugate acid

Importance of Buffers in the Body

• Enzymes are sensitive to pH
• Intracellular and extracellular fluids maintain a near constant pH
• The body is protected from pH changes resulting from continuous production of acids and bases through metabolic processes
• Organisms first line of defense against pH changes is provided by buffer systems

Biological Buffers

• Examples: HCO3-, Phosphate, proteins
• Proteins contain amino acids and functional groups
• Phosphate groups of nucleotides function as weak acids

Phosphate Buffer System

• Major intracellular buffering systems
• Acts in cytoplasm of all cells
• Consists of H₂PO₄⁻ as proton donor and HPO₄²⁻ as proton acceptor
• Maximally effective between pH 5.9 and 7.9 ( pKa ~ 6.86)

Bicarbonate Buffer System

• Main blood plasma buffer
• Consists of H₂CO₃ as proton donor and HCO₃⁻ as proton acceptor
• Complex because carbonic acid is formed by reaction of CO₂ and water
• pH depends on H₂CO₃ (dissolved CO₂) and HCO₃⁻

Human Blood Plasma pH

• Normal pH is ~7.4
• Changes in pH can cause cell damage or death in certain health conditions

Clinical Disorders in Acid-Base Balance

• Respiratory acidosis: alveolar hypoventilation, airway obstruction, neuromuscular disorders
• Respiratory alkalosis: hyperventilation due to anxiety, salicylate poisoning, fever, high altitude
• Metabolic acidosis: excess lactic acid, acetoacetic acid, β-hydroxybutyric acid, ingestion of salicylates, ethylene glycol, or methyl alcohol
• Metabolic alkalosis: intake of alkaline materials, abnormal loss of acid (prolonged vomiting)

Summary

• Water is a polar molecule with unique properties
• Most metabolic processes occur in an aqueous environment
• Numerous weak, non-covalent interactions influence macromolecule folding (e.g., proteins, nucleic acids)

Summary (cont.)

• A weak acid (or base) and its salt resist changes in pH due to the addition of H⁺ or OH⁻; mixture functions as a buffer
• Phosphate and bicarbonate buffer systems maintain optimal (physiological) pH in cells and tissues (~pH 7) which is optimal for enzymatic activity

Test your knowledge on the properties of water and its critical role in biochemical reactions. This quiz covers topics such as hydrogen bonding, pH, buffers, and the importance of water in living systems. Perfect for students in the Medical Biochemistry & Genetics course.