Week 4 Energy and Enzymes Forms of Energy Laws of Thermodynamics Energy and chemical reactions ATP – an energy carrier ATP Hydrolysis ATP and Phosphorylation ATP Cycle Enzymes Activation Energy and Rate of reactions Enzymes Mechanism Regulation of enzymes Metabolic Pathways Feedback Inhibition

Forms of Energy Kinetic Energy Potential Energy Movement Thermal energy Light energy Potential Energy Positional energy Chemical energy

First Law of Thermodynamics Law of Conservation of Energy Energy can be neither created nor destroyed, but can be transformed from one form into another. Implication – must account for source and fate of all energy in biological systems

Second Law of Thermodynamics Law of Entropy Entropy (disorder) is tends to increase in closed systems “For a process to occur spontaneously, it most increase the entropy of the universe.”

Kinetic energy of movement Figure 5.10 Fuel Energy conversion Waste products Heat energy Carbon dioxide Gasoline   Combustion Kinetic energy of movement Oxygen Water Energy conversion in a car Heat energy Figure 5.10 Energy transformations in a car and a cell Cellular respiration Glucose Carbon dioxide   ATP ATP Oxygen Energy for cellular work Water Energy conversion in a cell 5

Chemical Reactions and Energy Hydrolysis Reaction Maltose + H2O 2 Glucose 23 kcal/mol Dehydration Reaction 2 Glucoses Maltose + H2O 23 kcal/mol

Endergonic and Exergonic Reactions Spontaneous Reactions Endergonic Reactions Non-spontaneous Reactions

Endergonic and Exergonic Reactions Endergonic Reaction - nonspontaneous 3.4 kcal/mol Exergonic Reaction - spontaneous 7.2 kcal/mol

Overall still exergonic Coupled Reactions 7.2 kcal/mol 3.8 kcal/mol 3.4 kcal/mol Overall still exergonic spontaneous

ATP Hydrolysis

Graphic Analysis of coupled reactions Endergonic Reaction Exergonic Reaction Coupled Reaction Glutamate, Ammonia ATP Glutamine, ADP + P ATP Potential Energy of Molecules Potential Energy of Molecules Potential Energy of Molecules Glutamine Glutamate + Ammonia ADP + P Reactants Products Reactants Products Reactants Products How the cell provides energy for non spontaneous reactions.

ATP’s Energy Transferred by Phosphorylation

Energy from exergonic reactions Energy for endergonic reactions ATP Phosphorylation Hydrolysis Energy from exergonic reactions Energy for endergonic reactions Figure 5.12C The ATP cycle ADP P 13

Speed of Exergonic Reactions Paper + Oxygen Potential Energy of Molecules C20 Reactants Products Why are some spontaneous reactions very slow?

Speed of Spontaneous Reactions Activation energy barrier Enzyme Activation energy barrier reduced by enzyme Reactant Reactant Energy Energy Figure 5.13A The effect of an enzyme in lowering EA Products Products Fast Spontaneous Reactions Slow spontaneous Reactions 15

C20 Exergonic Reaction Potential Energy of Molecules Activation Energy Paper + Oxygen Potential Energy of Molecules C20 Reactants Products

How Enzymes speed up slow reactions Activation energy barrier Enzyme Activation energy barrier reduced by enzyme Reactant Reactant Energy Energy Figure 5.13A The effect of an enzyme in lowering EA Products Products Without enzyme With enzyme Enzymes reduce the activation energy of exergonic reactions. 17

Enzyme available with empty active site Figure 5.14_s4 1 Enzyme available with empty active site Active site Substrate (sucrose) 2 Substrate binds to enzyme with induced fit Enzyme (sucrase) Glucose Fructose H2O Figure 5.14_s4 The catalytic cycle of an enzyme (step 4) 4 Products are released 3 Substrate is converted to products 18

Normal binding of substrate Figure 5.15A Substrate Active site Enzyme Allosteric site Normal binding of substrate Competitive inhibitor Noncompetitive inhibitor Figure 5.15A How inhibitors interfere with substrate binding Enzyme inhibition 19

Ibuprofen (like aspirin) is a competitive inhibitor Figure 5.16 Ibuprofen (like aspirin) is a competitive inhibitor of an enzyme COX-2 which triggers the inflammatory response in tissues. Figure 5.16 Ibuprofen, an enzyme inhibitor 20

Metabolic Pathways Isoleucine pathway

Glycolysis

Feedback inhibition Enzyme 1 Enzyme 2 Enzyme 3 A B C D Reaction 1 Figure 5.15B Feedback inhibition Enzyme 1 Enzyme 2 Enzyme 3 A B C D Reaction 1 Reaction 2 Reaction 3 Starting molecule Product Figure 5.15B Feedback inhibition of a biosynthetic pathway 24

Feedback Inhibition Final product of the pathway – isoleucine is a non-competitive inhibitor of the first enzyme of the pathway