Topic 8

• Metabolism


  the totality of an organism's chemical reactions
• 2 types of metabolic pathways


  chains and cycles
• example of chain pathway


  glycolysis
• example of cycle pathway


  krebs cycle and calvin cycle
• How are metabolic pathways catalysed?


  enzymes
• activation energy

  the minimum amount of energy required to start a chemical reaction

  
• Enzymes lower...


  the activation energy of a reaction
• an exzyme catalysed reaction simply


  reduces the effort/energy needed for a reaction to occur meaning the reaction occurs at a faster rate than a normal reaction
• Reactant


  a substance that takes part in and undergoes change during a reaction.
• exergonic reaction


  If the reactants contain more energy than the products, the free energy is released into the system These reactions are usually catabolic (breaking down), as energy is released from broken bonds within a molecule

  
• endergonic reaction


  If the reactants contain less energy than the products, free energy is lost to the system These reactions are usually anabolic (building up), as energy is required to synthesise bonds between molecules

  
• Ea


  activation energy
• catabolic reactions


  break down large chemicals and release energy
• anabolic reactions


  build up large chemicals and require energy
• enzyme inhibitors


  a molecule that disrupts the normal reaction pathway between an enzyme and a substrate
• Enzyme inhibitors can be either


  competitive or non-competitive depending on their mechanism of action
• Normal Enzyme Reaction


  In a normal reaction, a substrate binds to an enzyme (via the active site) to form an enzyme-substrate complexThe shape and properties of the substrate and active site are complementary, resulting in enzyme-substrate specificityAs a consequence of enzyme interaction, the substrate is converted into product at an accelerated rate
• competitive inhibition


  structurally similar to the substrate directly blocks the active site increasing the substrate concentration will reduce the effect of competitive inhibition

  
• non-competitive inhibitor


  it is not structurally similar to the substratebinds to the allosteric site causes a conformational change in the active site, so that the substrate cannot bind increasing substrate concentration has no effect on the level of inhibition

  
• feedback inhibition


  a form of negative feedback / end-product inhibition by which metabolic pathways can be controlled

  
• what happens with end product inhibition?


  the product of a reaction acts as the inhibitor (via non competitive inhibition)the product therefore regulates the rate of it's own production
• End-product inhibition functions to ensure levels of an essential product are always tightly regulated: If product levels build up...


  the product inhibits the reaction pathway and hence decreases the rate of further product formation
• End-product inhibition functions to ensure levels of an essential product are always tightly regulated: If product levels drop...


  the reaction pathway will proceed unhindered and the rate of product formation will increase
• example of competitive inhibition


  relenza - blocks enzymes active site and prevents viral release
• Example of non-competitive inhibition


  cyanide - protein carriers are used in the electron transport chain, cyanide breaks bonds with protwin carrier (changes conformation), preventing protein shuttling and and ATP production
• example of feedback inhibition

  isoleucine - threonine is converted into isoleucine (end product) by an enzyme, isoleucine then binds to the allosteric site and blocks activity, isoleucine synthesis inhibits further production of isoleucine

  
• Isoleucine


  essential amino acid
• The rate of an enzyme-catalysed reaction can be calculated and plotted according...


  to the time taken for the reaction to proceed
• Rate of reaction formula

  1 / time taken (s)
• enzyme kenetics


  In enzyme kinetics, the reaction rate is measured and the effects of varying the conditions of the reaction are investigated.
• Both competitive and non competitive inhibitors


  effect the kinetics of an enzyme-catalysed reaction,by reducing the rate of reaction by limiting the amount of uninhibited enzyme available for reaction but in different ways
• Competitive inhibitors impacting enzyme kenetics/rate of reaction


  Bind directly to the active site and hence exist in direct competition with the substrateIncreasing substrate levels will increase the likelihood of the enzyme colliding with the substrate instead of the inhibitorThe maximum rate of enzyme activity (Vmax) can still be achieved, although it requires a higher substrate concentration

  
• Non-competitive inhibitor impacting enzyme kenetics/rate of reaction


  Bind to an allosteric site and hence do not exist in direct competition with the substrateIncreasing substrate concentrations will not effect the level of inhibition caused by the non-competitive inhibitorThe maximum rate of enzyme activity (Vmax) is therefore reduced

  
• how can inhibitors be used to treat pathogenic diseases?


  by targeting the enzymes involved
• how to find inhibitors for disease causing enzymes?


  pathogenic enzymes may be screened against a bioinformatic database to idenitfy inhibitors, new inhibitor compounds can also be made through combinatorial chemistry and computer modelling
• Drug treatment of malaria

  indentify's inhibitors specific to enzymes involved in the malarial parasite life cycle through both database mining and computer modeling and combinatorial chemistry to find a competetive inhibitor for the enzymes active site
• cell respiration


  the process by which organisms transform the energy contained in macromolecules into ATP
• Phosphorylation of molecules...


  makes them less stable
• ATP


  a high energy molecule that functions as an immediate power source for cells

  
• hydrolysis reaction


  A chemical reaction that breaks apart a larger molecule by adding a molecule of water