Biochemistry

Proteins, enzymes and the metabolic pathways that power the cell

About this course

Biochemistry from water and pH to integrated metabolism — protein structure and folding, binding, enzyme kinetics and regulation, bioenergetics, the central pathways and photosynthesis, and metabolic control.

What you will be able to do

  • Use pH and buffer calculations to predict the ionisation of biological molecules
  • Analyse ligand binding and cooperativity from binding curves
  • Derive and apply Michaelis–Menten kinetics and distinguish types of inhibition
  • Trace carbon and energy through glycolysis, the TCA cycle and oxidative phosphorylation
  • Explain how metabolic flux is regulated and controlled across the cell and body

What this course covers

  • Beta-oxidation and the palmitate ATP ledger
  • Fat vs. glucose energy density per carbon and per gram
  • Fat cannot become glucose: the metabolic asymmetry
  • Energy density of stored fuels: the water penalty
  • The fasting switch: glycogen, protein, and ketones
  • Nitrogen disposal: the urea cycle cost
  • Marathon worked example: rate limits and the glycogen wall
  • ATP value as a maintained displacement
  • Chemical basis of ATP's free energy
  • The phosphate compound ladder and coupling
  • Why coupling requires a shared intermediate
  • Redox potentials and the electron transport chain
  • The ATP stoichiometry debate
  • The daily ATP budget and turnover scale
  • Dissociation constant and the hyperbola
  • Measuring a KD: methods and pitfalls
  • Hill equation and the sigmoid
  • What Hill's exponent actually measures
  • Bohr effect and allosteric levers (BPG)
  • MWC two-state census model
  • Capstone: altitude, BPG response, and fetal handoff
  • Titration curve and pKa measurement
  • Water dissociation and the pH scale
  • Water as biochemical solvent
  • Henderson–Hasselbalch equation
  • Buffer capacity (Van Slyke's β)
  • Blood bicarbonate as an open buffer system
  • Phosphate buffer worked example
  • Insulin-glucagon ratio as the metabolic switch
  • Glycogen store size and the day-scale fuel budget
  • Phosphorylation as a regulatory switch
  • Gluconeogenesis cost and the Cori cycle tax
  • Substrate cycles: sensitivity and heat
  • Three-layer, two-organ regulatory architecture
  • Two metabolic gauges: fructose-2,6-bisphosphate and AMP kinase
  • Amino acid structure and isoelectric point
  • The twenty amino acids: four side-chain families
  • Protein charge as a sum of sigmoids
  • pKa shifts in folded proteins
  • Hydropathy scale and membrane helix detection
  • Peptide bond planarity and backbone geometry
  • Full nine-group peptide worked example
  • Glycolysis ATP ledger and free energy profile
  • Substrate-level phosphorylation mechanism
  • The three irreversible doors and seven reversible hinges
  • Near-equilibrium flux: fraction, enzyme excess, and flux control
  • Fermentation: NADH debt, yield, and the Warburg effect
  • Phosphofructokinase throttle and adenylate kinase amplification
  • Sprinting muscle: worked ledger application
  • Steady-state derivation and the Michaelis-Menten hyperbola
  • Initial-rate measurement conditions
  • Kcat, KM, and honest curve fitting
  • Specificity constant and the diffusion limit
  • Validity of Michaelis-Menten kinetics inside the cell
  • Integrated rate equation and the progress curve
  • Full worked enzyme characterisation
  • The fold as a marginal free-energy minimum
  • The hydrophobic effect: entropy of water
  • Temperature dependence and the stability parabola
  • Hydrogen bonds: architecture, not driving force
  • Two-state melting and the Van't Hoff enthalpy
  • Anfinsen's principle and its modern scope
  • Levinthal's paradox and the folding funnel
  • The three families of enzyme inhibition
  • Reciprocal (Lineweaver-Burk) plot signatures
  • KI versus IC50: the molecule's number and the assay's number
  • Mechanistic basis of non-competitive inhibition
  • Drug dose from KI: methotrexate and the statins
  • Covalent inhibition: a rate, not a constant
  • Worked example: classifying, quantifying, and dosing an inhibitor
  • Flux Control Coefficient and Summation Theorem
  • Doubling One Enzyme vs. Doubling All
  • Control vs. Regulation: PFK Paradox
  • Feedback and Substrate Saturation Redistribute Control
  • Knockouts, Drugs, and the Recessive Disease Argument
  • Flux–Enzyme Hyperbola and the Half-Point
  • Metabolic Control Analysis as a Design and Engineering Recipe
  • Historical discovery of the Krebs cycle
  • The cycle's carbon and electron ledger
  • Pyruvate dehydrogenase complex
  • Isotope proof and the fat-to-sugar prohibition
  • Free-energy analysis of cycle steps in the cell
  • NADH as the cycle's throttle
  • Whole-body cycle accounting: the breath calculation
  • Whole-body ATP budget: moles, mass, and power
  • Indirect calorimetry and the respiratory quotient
  • Budget closure and the 'calories' misconception
  • Integrating the fast: fuel stores over 60 days
  • The brain's fixed 20-watt demand and the ketone switch
  • Marathon energy budget and the glycogen wall
  • Frayne/Weir worked example and course spine closure
  • Electron transport chain: redox ladder and proton pumping
  • Mitchell's chemiosmotic hypothesis and its experimental proof
  • ATP synthase mechanism and C-ring stoichiometry
  • Turbine thermodynamics and respiratory control
  • Glucose ATP ledger: 32, not 38
  • Uncouplers and thermogenic short-circuiting
  • Worked example: proton current, yeast ring, and stall PMF
  • Eyring rate equation and barrier arithmetic
  • Transition-state binding as the source of catalytic power
  • Enzyme catalysis and thermodynamic equilibrium
  • Allostery and feedback inhibition in ATCase
  • Validity of the MWC two-state model for ATCase
  • Phosphorylation switch and zero-order ultrasensitivity
  • Synthesis: handles, gains, and the regulated pathway
  • Origin of Photosynthetic Oxygen: Water Splitting
  • The Z Scheme: Two Photons Per Electron
  • Why Two Photosystems Are Required
  • The Calvin Cycle: ATP and NADPH Ledger
  • RuBisCO: Slow Speed and Oxygenase Activity
  • Sunlight-to-Biomass Efficiency Chain
  • Worked Example: Leaf Photon Budget and Daily Yield

Syllabus

  1. Water and Proteins

    1. L1 · Water, pH and Buffers
    2. L2 · Amino Acids and the Peptide Bond
    3. L3 · Protein Folding

  2. Binding and Enzymes

    1. L4 · Binding and Cooperativity
    2. L5 · Enzyme Kinetics
    3. L6 · Inhibition
    4. L7 · Catalysis and Allostery

  3. Energy Metabolism

    1. L8 · Bioenergetics
    2. L9 · Glycolysis
    3. L10 · Pyruvate Dehydrogenase and the TCA Cycle
    4. L11 · Oxidative Phosphorylation
    5. L12 · Photosynthesis

  4. Integration and Control

    1. L13 · Fat and Nitrogen
    2. L14 · Metabolic Regulation
    3. L15 · Control and Flux
    4. L16 · The Integrated Cell and Body