Energy & Metabolism

• Catabolic pathways


  Release energy and involve the breakdown of molecules
• Anabolic pathways


  Require energy and are involved in the synthesis of complex molecules from simpler molecules
• Carbohydrate classificationsThe monosaccharides commonly found in humans are classified according to the number of carbons they contain in their backbone structures. The major monosaccharides contain four to six carbon atoms.
• Oxidative catabolism of glucose


  Serves 2 functions - The production of 'free energy' in the form of ATP, The production of intermediates from glycolysis and the TCA cycle to provide material for other metabolic pathways
• Oxidative metabolism


  A chemical process in which oxygen is used to make energy from carbohydrates, also called aerobic metabolism, aerobic respiration, and cell respiration
• Glucose


  Energy storage molecule
• Energy requirements of the cell via ATP


  Material requirements of the cell
• The ultimate fate of glucose

  1. This energy can be used in the form of ATP to meet the body's requirements

  2. C6H12O6 + 6O2 -> 6CO2 + 6H2O

  3. The standard free energy change (G°´) for this reaction is -2834 kJmol-1 (kJ/mol)

  4. Biology cannot use all of this energy in one go. Instead it uses a controlled release approach in which each enzyme performs a small step hence multiple steps required thus forming a metabolic pathway

  5. Energy released from fuel oxidation that is not used for work is transformed into and released as heat
• Change in Gibbs free energy


  Used to characterise individual steps along a metabolic pathway
• ΔG°´


  Provides information about what happens to the free energy (energy available to do work) during a chemical/biological reaction
• Exergonic


  If ΔG°´ is negative, free energy is released - the reaction is said to be exergonic
• Endergonic


  If ΔG°´ is positive, free energy is absorbed - the reaction is said to be endergonic
• Biological uses of the release of energy

  • Biochemical work - energy-requiring chemical reactions
  • Heat generation
  • Transport work - establishment of ionic gradients
  • Mechanical work - muscle contraction
• The heart is a specialist in the transformation of ATP chemical bond energy into mechanical work. If the heart were not able to regenerate ATP, all of its ATP would be hydrolysed in less than 1 min - absolute requirement for oxidative phosphorylation
• Equilibrium Constant (Kc)


  The ratio of the concentration of products to reactants in a balanced chemical reaction
• Reaction Quotient (Q)


  The ratio of the concentrations of products to reactants at any given time
• At equilibrium, ΔG = 0
• van't Hoff isotherm


  Equation that links ΔG°, R, T and Kc: ΔG° = -RT ln K
• Comparison of ΔG°, ΔG°´ and ΔG

  • ΔG° - standard free energy change at pH 0, 25°C, 1 atm
  • ΔG°´ - standard free energy change at pH 7, 25°C, 1 atm
  • ΔG - free energy change at cellular conditions, pH 7.34, 37°C, variable concentrations
• If ΔG is negative


  The equilibrium lies in favour of the products
• If ΔG is positive


  The equilibrium lies in favour of the reactants
• If ΔG is large and negative


  The reaction equilibrium is essentially irreversible
• If ΔG is large and positive


  The reaction will not proceed
• Le Chatelier's Principle - Any deviation from equilibrium stimulates a process that tends to restore the system to equilibrium
• Many metabolic reactions are close to their equilibrium concentration hence if [substrate] increases, the reaction proceeds to the right i.e., more products are made
• In the cell some reactions are far from equilibrium as they essentially proceed in only one direction - a key to metabolic flow
• In energy producing and energy utilising metabolic pathways, ΔG values are additive
• Coupled reactions drive endergonic processes

  ATP + glucose -> glucose-6-P + ADP (ΔG°´ = -16.7 kJ/mol)
• Metabolic pathways are irreversible
• Every metabolic pathway has a first committed step
• Feedback inhibition


  The product of a late or last step frequently acts as an inhibitor of the first committed step. Hence, end product controls its own synthesis.
• All metabolic pathways are regulated
• Glucose + ATP -> glucose-6-P + ADP


  1. Two isoforms - glucokinase and hexokinase

  2. Hexokinase is saturated by substrate under physiological conditions and is inhibited by its end products ADP and glucose 6-P resulting in a steady supply rate for glycolysis intermediates

  3. After meals, it is the liver glucokinase that deals with the high glucose levels as the liver is responsible for maintaining blood glucose levels. Also other tissues get access to the glucose first before the glucose storage function of the liver kicks in.
• In eukaryotes, metabolic pathways occur in specific cellular locations
• Metabolic pathways are controlled by switching on/off the gene for the first enzyme
• Control of flux is based on the amount of key enzymes and the presence of tissue specific isoenzymes and their regulation once made
• Enzymes often act in groups or as multi-enzyme complexes
• Two ways to regulate a metabolic pathway

  • End product feedback inhibition - quick and subtle form of control
  • Gene regulation - slower form of control but can greatly enhance the amount of final product
• Overview of Metabolic Pathways

  1. Irreversible, exergonic, committed step

  2. Coupled reactions drive endergonic steps

  3. Energy flow is downhill

  4. Reformation uses a different pathway
• Metabolic pathway


  A linked series of chemical reactions occurring within a cell. The reactants, products, and intermediates of an enzymatic reaction are known as metabolites, which are modified by a sequence of chemical reactions catalyzed by enzymes.