Metabolism Overview

• Metabolism: a collection of coupled and interlinked series of chemical reactions that start with a particular molecule which is converted to another molecule or molecules.
• What is the definition of metabolism?

  interlinked chemical reactions starting with a specific molecule and converted to another
• Main metabolism functions:

  -       Extract biologically useful energy from the cell’s environment

  -       Synthesise the building blocks of the cell
• What do catabolic reactions do?

  Extract biologically useful forms of energy
• What do anabolic reactions do?

  Synthesise complex molecules from simple ones; energy input required
• What are the 6 classes of metabolic reactions?

  Redox, ligation, isomerisation, group transfer, hydrolysis and lyase catalysed
• Redox reactions involve electron transfer e.g., loss or gain of hydrogen

  -       Oxidation = loss of electrons; loss of hydrogen

  -       Reduction = gain of electrons; gain of hydrogen

  Example:

  -       Succinate is oxidised to fumarate; FAD reduced

  o   Catalysed by succinate dehydrogenase

  A) fumarate

  B) succinate

  
• Ligation reactions are energy dependent

  Example:

  • conversion of pyruvate to oxaloacetate
  • energy from ATP hydrolysis used to form C-C bond from CO2
  • catalysed by pyruvate carboxylase

  A) pyruvate

  B) oxaloacetate

  
• Isomerisation reactions involve the re-arrangement of bonds in a substrate

  • same molecular formula but different spacial arrangement of atoms

  Example:

  • conversion of citrate to isocitrate
  • catalysed by aconitase

  A) citrate

  B) isocitrate

  
• Group transfer reactions involve the transfer of chemical groups between molecules e.g., high energy phosphate

  Example:

  • conversion of glucose to glucose-6-phosphate
  • catalysed by hexokinase
  • glucose energised by phosphate addition via phosphor-anhydride bond

  A) glucose

  B) glucose-6-phosphate

  
• Hydrolysis is the breakdown of a bond using a molecule of water.

  Example:

  • hydrolysis of a peptide bond
• Lyase catalysed reactions

  • reversible; catabolic or anabolic
  • catabolic = removal of C-C to form C=C
  • anabolic = condensation; formation of C-C
  • not ATP dependent

  Example:

  • fructose 1,6-bisphosphate to DHAP and GAP in glycolysis
  • catalysed by aldolase

  A) fructose 1,6-bisphosphate

  B) DHAP

  C) GAP

  
• Activated carriers

  • 'activated' as an energy transfer is involved
• Name 4 examples of activated carriers

  ATP, NADH, FADH2, Acetyl CoA
• ATP = activated carrier of phosphate groups; release is energetically favourable

  • highly complex molecule
  • anhydride bond important for energy transfer
• NADH and FADH2 = activated carriers of electrons

  • ring structures alternate between double and single bonds to accept and donate electrons
• Acetyl CoA = activated carrier of acetyl unit

  • thioester bond to a carbon unit; similar to phosphor-anhydride bond as bond breaking is exergonic
• Activated carriers are conserved through evolution

  • absence of catalysts; kinetically stable + thermodynamically unstable
  • enables enzymes to control flow of electrons (reducing power) and free energy; release of energy controlled by enzymes
  • in absence of a catalyst:

  o   NADH + FADH2 = resist oxidation and release of electrons

  o   ATP + acetyl CoA = hydrolysed slowly

  • moved about by cell without reacting; only react when enzyme is present; energy stored without risk of spontaneous release
• Carbon fuels are oxidised to CO2

  • Free energy associated with oxidation of single carbon compounds
  • Energy stored in C-H bonds
  • Rearrangement of electrons (movement from C-H to O) causes the release of energy; released as heat; not useful to cells

  Fuel molecules are often complex

  • the more reduced, the more energy is stored as more electrons can be rearranged towards oxygen
  • glucose oxidation releases heat, energy from electron rearrangement captured by ATP
• Oxidative phosphorylation = final stage of fuel catabolism

  • electron transport chains rearrange electrons towards oxygen
  • leads to phosphorylation of ADP to ATP
  • electrons donated to form water
  • energy captured and converted to ATP production