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Metabolism Lecture 5, part 2 Fall 2008
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Rate of Chemical Reactions
1 ΔG = ΔH - T ΔS If ΔG is less than 0, reaction is spontaneous = exergonic Net release of free energy If ΔG is greater than 0, reaction is not spontaneous = endergonic Absorbs free energy from its surroundings Stores free energy in molecules ΔG does not specify rate of reaction Fig. 8.6
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Rate of Chemical Reactions
2 Rate for a spontaneous reaction may be very slow e.g., hydrolyses of sucrose ΔG of -7kcal/mol May not happen for years without enzyme Fig. 8.13
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What is an Enzyme? Macromolecule that acts as a catalyst
3 Macromolecule that acts as a catalyst Catalyst – chemical agent Speeds up reaction Not consumed in reaction Enzymes allow for regulation of metabolic pathways Many enzymes are proteins “-ase”
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Protein Structure Primary structure Polypeptide chain Amino acids
4 Primary structure Polypeptide chain Unique sequence of amino acids Amino acids Basic structure of each amino acid is the same Unique side group = R group Nonpolar Polar Electrically charged See Fig. 5.17
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Protein Structure Secondary Structure
5 Protein Structure Secondary Structure Reactions between polypeptide backbone (not side groups) Hydrogen bonding Alpha helix Beta pleated sheets Fig. 5.21
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Protein Structure Tertiary Structure
6 Tertiary Structure Interactions between side chains (R groups) Hydrophobic reaction Amino acids with nonpolar side chains end up folded in clusters at center of protein Weak interactions Van der Waals interactions Hydrogen bonds Ionic bonds Covalent bonds Disulfide bridges Fig. 5.21 Van der Waal – regions of positive and negative – only occur when molecules very close together Electron distribution not symmetrical even in nonpolar colvalent bonds
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Protein Structure Quaternary Structure
7 Quaternary Structure Aggregation of two or more polypeptide subunits Hydrogen bonding Disulfide Bridges Ionic bonding Van der Waals interactions Fig. 5.21
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Protein Structure Denaturation Loss of structure in a protein
8 Denaturation Loss of structure in a protein Biologically inactive May be reversible Fig. 5.23
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Protein Structure Chaperonins
9 Chaperonins Provides ideal environment for protein to fold Fig. 5.24
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Chemical Reactions & Activation Energy
10 Chemical reactions Bonds breaking & forming Molecules need to be brought to an highly unstable state before bonds broken/reformed Contortion Requires absorbing energy from its surroundings Activation energy - EA (free energy of activation) The amount of energy that reactants must absorb before a chemical reaction will start
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Chemical Reactions & Activation Energy
11 Activation energy (EA) Free energy content of reactants increasing Transition state Highly unstable Bonds able to be broken Energy released as bonds reformed in products Exergonic reaction Fig. 8.14
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Chemical Reactions & Activation Energy
12 Activation energy Barrier that determines rate of reaction “height” of barrier variable How to lower the activation energy? Apply heat (thermal energy) Increase speed/collision of molecules Movement stresses bonds – more likely to break Problems with applying heat in cells? Not ideal for cells - denatures proteins Would speed up all reactions in cells – non specific With heat, all molecules rich in free energy would spontaneously decompose
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Chemical Reactions & Activation Energy
13 Use a catalyst : Enzymes Lowers EA barrier Allows for bonds to break at lower temperature Allow for regulation of metabolic activity High specificity Able to be used repeatedly Enzymes do not change the ΔG of a reaction Fig. 8.15 Enzymes cannot change an endergonic reaction to an exergonic reaction
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How Enzymes Work Forms enzyme-substrate complex
14 Forms enzyme-substrate complex Binds to substrate in active site Substrate = reactants Highly specific Shape critical for recognition/fit Active site Region where substrate binds& catalysis occurs Multiple weak interactions w/side chains (R groups) of amino acids Induced fit Change in shape of an active site Binds more closely to substrate The specific portion of an enzyme that binds the substrate by means of multiple weak interactions and that forms a pocket in which catalysis occurs While enzyme and substrate are joined the catalytic action of the enzyme converts the substrate to the product of the reaction Fig. 8.16
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15 How Enzymes Work See Fig. 8.17
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How Enzymes Work 16 R groups of amino acids of active sites catalyze conversion of substrates to products Extremely rapid 1000 substrate molecules/sec/enzyme Mechanisms for catalysis Act as template to orient substrate Stress chemical bonds of substrate Provide a favorable microenvironment Participate directly in catalytic reaction May involve bonding between R group and substrate
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How Enzymes Work Rates limited by Amount of substrate Amount of enzyme
17 Rates limited by Amount of substrate Amount of enzyme Enzyme saturation All enzymes have active sites engaged Rate will not increase past saturation point
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Effects of Local Conditions on Enzyme Activity
18 Effects of Local Conditions on Enzyme Activity Temperature pH Cofactors Inhibitors/Activators
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Effects of Temperature & pH
19 Optimal conditions of enzymes vary Temperature pH Fig Increasing temperature, increasing rate of reaction More collisions Sharp decline – too much thermal agitation for weak bonds of active site Eventually denatures
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Regulation of Enzymes Cofactors
20 Cofactors Small molecules (non-proteins) needed for the enzyme to function properly May be bound to enzyme permanently or be transient Necessary for some enzymatic reactions E.g., iron, zinc, copper, many vitamins Coenzyme – when the cofactor is an organic molecule
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Regulation of Enzymes Enzyme inhibitors Competitive inhibitors
21 Enzyme inhibitors Competitive inhibitors Compete with substrate for active site Slows productivity Reversible Noncompetitive inhibitors Binds to enzyme away from active site Changes conformation of enzyme/active site Less effective at catalysis Many toxins irreversible enzyme inhibitors Sarin Fig. 8.19
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Regulation of Enzymes Allosteric regulation
22 Allosteric regulation The binding of a regulatory molecule at one site on a protein that affects the function of the protein at another site Most allosteric proteins have 2 or more subunits Activator stabilizes active form Inactivator stabilizes inactive form Fig. 8.20 Quaternary structure
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Regulation of Enzymes Cooperativity Type of allosteric activation
23 Cooperativity Type of allosteric activation Substrate binding causes a shape change in protein that facilitates binding of additional substrates Typically causes shape change Fig. 8.20
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Regulation of Enzymes Feedback inhibition
24 Fig. 8.22 Feedback inhibition Metabolic pathway switched off by the inhibitory binding of its end product to an enzyme that acts early in the pathway Why do this? Saves energy, chemical resources
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Regulation of Enzymes 25 Localization of enzymes Fig. 8.23
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