1 - Overview of Metabolism

• Metabolism is a collection of coupled and interlinked series of chemical reactions that converts molecules into different molecules
• Main functions of metabolism:

  • Extract biologically useful energy from the cells' environment
  • Use the energy to synthesise the building blocks of the cell (convert simple molecules to complex macromolecules e.g. amino acids into proteins)
• Metabolism is made of anabolic and catabolic reactions
• Catabolic reactions extract biologically useful forms of energy from carbon fuels e.g. glucose

  
• Anabolic reactions synthesise/generate complex structures or molecules from simple ones, requiring an input of energy (from catabolism)

  
• 6 types of enzyme catalysed reaction in metabolism = "OILHAG"

  1. Oxidation-Reduction
  2. Isomerisation
  3. Ligation (requiring ATP cleavage)
  4. Hydrolytic
  5. Addition/removal of functional groups
  6. Group transfer
• An example of an oxidation-reduction reaction (electron transfer) is the oxidation of succinate into fumarate, while FAD is reduced to FADH2 via succinate dehydrogenase

  
• Carbon dioxide is "pretty much" energy inert, therefore energy must be put into the system to utilise it to form C-C bonds
• An example of a ligation reaction is the ligation of 3C pyruvate into 4C oxaloacetate via pyruvate carboxylase

  
• An example of an isomerisation reaction is the isomerisation of citrate to isocitrate via aconitase by changing the position of hydroxyl and hydrogen groups

  
• An example of a group transfer reaction is the donation of high-energy phosphate from ATP to glucose to form Glucose 6-Phosphate and ADP via hexokinase

  
• By phosphorylating glucose (forming Glucose 6-Phosphate), a negative charge is placed on the glucose in order to trap it in the cell
• The phosphorylation of glucose using ATP is an energetically favourable reaction
• An example of a hydrolysis reaction is the hydrolysis of a peptide forming a product with a C terminus (COO-) and a product with an N terminus (NH3+) using water

  
• An example of a lyase catalysed reaction is the formation of dihydroxyacetone phosphate (DHAP) and glyceraldehyde 3-phosphate (GAP) from fructose 1,6-bisphosphate (F-1,6-BP) via aldolase
• Activated carriers have been conserved through evolution
• ATP is an activated carrier of phosphoryl groups

  
• Breaking the high-energy covalent phosphoanhydride bond in ATP to form ADP is energetically favourable and releases energy for anabolic reactions. This is because there is electrostatic repulsion as the phosphoanhydride bonds are short, holding negatively charged molecules close together
• FADH2 is an activated carrier of electrons

  
• Acetyl CoA is an activated carrier of acetyl units. It has an ADP-like structure and has bonds that are energetically favourable to break

  
• Activated carriers have been conserved through evolution because they are thermodynamically unstable in the absence of specific catalysts (e.g. hydrolysis is associated with the release of large amounts of free energy), they are kinetically stable. This allows for their biological function as it allows the enzymes to control the flow of electrons (reducing power) and free energy
• In the absence of an enzyme, NADH and FADH will resist oxidation and the release of electrons
• In the absence of an enzyme, ATP and Acetyl CoA are hydrolysed slowly
• ATP hydrolysis is required for:

  • Motion
  • Active transport
  • Biosyntheses
  • Signal amplification
• ATP is synthesised by:

  • Oxidation of fuel molecules
  • Photosynthesis
• Carbon fuels are oxidised to CO2
• Each intermediate in the oxidation of carbon fuels have progressively less energy associated with them as the electrons have been moved from C-H bonds to oxygen

  
• Electronegative molecules such as Oxygen and Nitrogen have a higher attraction for electrons
• Electrons rearrange towards oxygen due to its high electronegativity

  
• The final stage of fuel catabolism is oxidative phosphorylation

  
• 3 broad stages of catabolism:

  1. Degradation of complex carbon fuels into smaller units
  2. Convergence to a few simple units
  3. Oxidation of acetyl unit to CO2, reduction of NAD+ and FAD, generation of H+ gradient and synthesis of ATP

  
• *ATP is an efficient phosphoryl group donor as it has a high phosphoryl transfer potential
• *ATP has a high phosphoryl transfer potential because:

  • Orthophosphate (Pi), one of the products of ATP hyrolysis, has a higher resonance stabilisation than any of the other ATP phosphoryl groups
  • Electrostatic repulsion of the triphosphate unit which carries 4 negative charges in close proximity at pH7. The repulsion between them is reduced when ATP is hydrolysed
  • There is an increase in entropy with 2 molecules as products rather than a single ATP molecule
  • Water binds to the hydrolysis products, ADP and Pi, stabilising them and making the reverse reaction unfavourable