BO101 Cell Biology - Lecture 5 - Energy & Enzymes PDF

Energy and enzymes BO101 Cell Biology - Lecture 5 Dr Andrew Flaus, Biochemistry Life is work ๏ Thermodynamics ‣ Laws of energy transformation ‣ Energy is the capacity to do work ๏ First law ‣ Energy can only be transferred, not created or destroyed ‣ Organisms obtain...

Energy and enzymes BO101 Cell Biology - Lecture 5 Dr Andrew Flaus, Biochemistry Life is work ๏ Thermodynamics ‣ Laws of energy transformation ‣ Energy is the capacity to do work ๏ First law ‣ Energy can only be transferred, not created or destroyed ‣ Organisms obtain all energy for life from the environment ๏ Second law ‣ Every energy transformation increases the entropy of the universe Campbell g 6.3 fi Biology struggles against disorder ๏ Chemicals cycle ‣ Matter cannot be created or destroyed (First law) ๏ All spontaneous changes have ΔG < 0 ‣ ΔG = ΔH - TΔS ΔG = free energy ΔH = total energy ΔS = entropy ๏ Energy ows towards disorder (Second law) Campbell g 1.9 fi fl  Cells require continuous inputs of energy to maintain their high level of organisation life is work Energy ow in ecosystems plants, algae all eukaryotes Campbell g 10.1 fi fl Free energy and spontaneous reactions ๏ Reactants have higher free energy (ΔG) ‣ Greater work capacity ๏ Products have lower ΔG ๏ Exergonic reaction ‣ Released free energy can be used to do work ‣ Free energy decreases in a spontaneous change ‣ Energy can be interconverted ‣ Opposite is endergonic reaction Campbell gs 6.5, 6.6 fi Transfer of energy drives biology Glucose, O2 anab olic p creat roces i work ng (local ses ing a ) orde gains r t entr opy catab olic p releas roces i n g e ses cellul n e rgy ar res piratio n CO2, H2O Campbell g 6.8 fi  Greek ‘kata’ = downward anabolism metabolic pathways that metabolic pathways that release energy consume energy by breaking down to synthesise complex molecules complex molecules to simpler molecules from simpler molecules catabolism Greek ‘ana’ = upward Campbell concept 6.1 Concept of metabolism ๏ Life requires energy ‣ Second law: Work must be performed against entropy ๏ Metabolism is an organised set of transformations ‣ First law of thermodynamics: Energy can only be interconverted ‣ Catabolism extracts energy and molecular parts in small steps ‣ Anabolism builds up more complex biomolecules Image from Tymoczko 2nd ed p218 ATP as energy currency to couple reactions catabolic anabolic Campbell gs 6.9, 6.12 fi ATP can drive endergonic reactions 1. Transfer of phosphate to another molecule 2. Causes chemical or structural change 3. ATP drives process ‣ ATP → ADP, phosphate release 4. Must regenerate ATP … ‣ Catabolism to provide energy ‣ Ultimate link to photosynthesis Campbell g 6.11 fi Coupling ATP to drive reactions ๏ ATP → ADP ‣ ΔG = ~-7 kcal/mol ‣ Strongly exergonic ‣ Can be coupled ‣ to endergonic reaction ๏ ATP driver mechanism ‣ Drive conformational change in an enzyme structure ‣ Addition of unstable phosphate group ๏ Speci city is required Campbell g 6.10 fi fi Enzymes direct biochemical reactions Enzymes and catalysis ๏ Increase rate of reaction ๏ Are not consumed ๏ Provide speci c surface for reaction to occur ๏ Can be linked in pathways ‣ Metabolism ‣ Signalling ‣ Information transfer Campbell gs 16.13, 16.15 fi fi Enzymes and catalysis ๏ Increase rate of reaction by providing lower energy path ‣ Activation energy barrier (EA) ๏ Chemical energy of reactants and products is unaffected ‣ Free energy change (ΔG 70ºC ๏ pH ‣ Normal = pH 6-8 ‣ Stomach = pH 2 ๏ Use of cofactors ‣ Vitamins ‣ Metal ions ‣ Small molecule chemicals Campbell g 6.17 fi Evolution can generate novel enzymes Change speci city of enzyme with a few amino acid differences can be close or far from active site Campbell g 6.19 fi fi Regulating enzyme activity Regulation of enzymes by inhibitors native competitive non-competitive enzyme Binds in active site Binds away from active site Blocks substrate access Affects enzyme shape reduced enzyme function Campbell g 6.18 fi Cooperativity ๏ Cooperativity ‣ Binding of one substrate alters binding of other substrates ‣ Requires multi-subunit enzyme ๏ Example: Hemoglobin ‣ 4 subunits ‣ Binds 4 x O2 ‣ Each O2 bound makes next O2 bindings easier Campbell g 6.20 fi Allostery ๏ Allostery ‣ Change in protein function by binding away from active site ‣ Affects enzyme structure ‣ Enables enzymes to be regulated ๏ Examples: ATP, ADP ‣ ADP activates several catabolic enzymes ‣ ATP inhibits several catabolic enzymes ‣ Not acting as energy currency in this case Campbell g 6.20 fi Using inhibition for feedback regulation ๏ Feedback inhibition ‣ End product inhibits early steps in pathway ๏ Example: Isoleucine ‣ Isoleucine amino acid made from threonine precursor ‣ Isoleucine inhibits rst enzyme in pathway Campbell g 6.20 fi fi Summary of lecture ๏ Thermodynamics ‣ First and second laws ‣ Life is work ๏ ATP as an energy currency ๏ Enzymes speed up reactions ‣ Catalysis in active site ‣ Conditions: temp, pH, cofactors ๏ Enzyme regulation ‣ Inhibition, cooperativity, allostery ‣ Feedback inhibition of pathways  Learning outcomes for lecture ๏ On successful completion of this lecture, you will be able to: ‣ Explain the rst and second laws of thermodynamics ‣ Justify the reason why catabolic metabolic pathways are core to understanding the biochemistry of living organisms ‣ Give examples of how enzyme structure enables catalytic activity ‣ Describe how catalytic activity is affected by conditions ‣ Illustrate competitive inhibition and non-competitive inhibition using diagrams ‣ De ne cooperativity and allostery ‣ Explain how enzymes can be regulated in order to control pathways fi fi