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Metabolism

  • Defined as: the sum of all the chemical reactions that take place in a cell or an organism
    • Catabolism: the metabolic pathways that release chemical energy by breaking down complex molecules to simple molecules
    • Anabolism: the metabolic pathways that take in energy and synthesise complex molecules from simple molecules

ATP – life’s universal currency of energy

  • Adenosine triphosphate, an example of catabolism and anabolism
    • Energy is trapped as ATP
      • Convenient form because it can store energy and is stable
      • Energy trapped in the high energy bonds of between the phosphate molecules in the triphosphate
        • ATP + H2O -> ADP + PO3 + energy
  • Uses of ATP:
    • Precursor for RNA/DNA synthesis
    • Energy
      • Energy from catabolism of ATP is released
      • Some energy is used to do cellular work: mechanical, transport, chemical
      • Energy from catabolism of ATP/glucose etc used to synthesise ATP from ADP and Pi
      • Dynamic process that makes and uses ATP all the time
  • Energy in vs out:
    • If energy in from food exceeds energy out, excess energy is stored and body mass increases
    • If energy out from exercise exceeds energy in, body stores are used and mass decreases

Organisms and their metabolic diversity

  • Life requires organisms to have energy and carbon
    • Energy:
      • Phototrophs – use light to get energy
      • Chemotrophs – use chemicals to get energy
    • Carbon:
      • Autotrophs – require CO2 only
      • Heterotrophs – one or more organic carbon sources
    • Plants – photo-autotrophs
    • Humans – chemo-heterotrophs

Aerobic and anaerobic

  • Aerobic – catabolism requiring oxygen - respiration
    • Glucose + 6O2 -> 6CO2 + H2O + energy
  • Anaerobic – catabolism that doesn’t require oxygen - fermentation
    • Glucose -> 2 C2H5OH + 2CO2 + energy
    • Glucose -> 2 lactate- + 2H+
  • Humans:
    • Proteins (amino acids) and fats can only been broken down by aerobic catabolism
    • Carbohydrates are normally broken down by respiration
      • In skeletal muscle (during intense/short duration exercise) and in RBCs fermentation takes place, glucose converted to lactate
    • Explains why tissues/cells die -> oxygen supply interrupted, no oxygen, no ATP, no energy = death

Krebs cycle

  • Glucose does not directly catabolise into oxygen and water
  • Involves redox reactions of NAD+ and NADH which are later re-oxidised using O2

Metabolic Control

  • Metabolic pathways are regulated according to cell needs
    • Achieved by feedback inhibition (a very general concept)
      • Process:
        • Product of process is created
        • Product acts as an inhibitor for one of the enzymes that activates the start of the process
          • Thus, the process is stopped
        • In this case: H inhibits E1
      • Product of pathway inhibits the pathway
        • Amount of product is limited since:
          • If there is a lot of product, pathway is off
          • If there is little of the product, pathway is on

Allosteric Enzymes

  • Enzymes that oscillate between an active and an inactive conformation
    • Have a quaternary structure
    • Activators and inhibitors bind and lock the enzyme in the active or inactive conformation
      • Bind at sites that are separate from the reactor sites
      • Can be structurally totally different from the enzyme substrate and therefore an enzyme can be regulated with molecules that don’t fit in the reactor site/aren’t substrates
  • ATP:
    • Catabolic: inhibited by ATP, activated by ADP or AMP
    • Anabolic: inhibited by ADP, AMP, activated by ATP
    • More generalised, often happens this way, activated by starting materials, inhibited by products

Where do these process happen?

  • Compartmentation
    • Mitochondria – the powerhouse of the cell
      • Catabolism, ATP production
    • Cytosol (cytoplasm) – the factory of the cell
      • Synthesis/anabolism, ATP utilisation

Catabolism and different fuels

  • Minimal pathways means minimal numbers of enzymes etc
    • Therefore lipids, proteins and carbohydrates converge into the same metabolic pathway for the final stages
  • Process:
    • Macromolecules -> digestion -> Building blocks -> funnelling of carbohydrates/proteins/fats (some ATP formed) -> common parts (some ATP formed) -> TCA cycle -> ATP
  • Tissue use of fuels:
    • All use carbohydrates
    • Brain/retina/RBCs cannot use fat/proteins -> glucose dependent
    • Skeletal muscles generate ATP faster when breaking down carbohydrates instead of fat/proteins
      • Therefore support a higher intensity of exercise using carbohydrates as a fuel
  • Note: thermodynamically favourable means a release of energy, unfavourable requires energy