6 An Introduction to Metabolism

Requirements of a Cell A way to encode/transmit information A membrane separating inside from outside ENERGY Adenosine Triphosphate (ATP) Universal currency of all cells Called the “energy coin” © 2016 Pearson Education, Inc.

Concept 6.1: An organism’s metabolism transforms matter and energy Metabolism: all of an organism’s chemical reactions Manages both “chemicals” and “energy” of the cell © 2016 Pearson Education, Inc.

Metabolic Pathways Enzyme 1 Enzyme 2 Enzyme 3 A B C D Reaction 1 Reaction 2 Reaction 3 Starting molecule Product Figure 6.UN01 In-text figure, metabolic pathway, p. 122 Metabolic pathway: begins with a specific molecule and ends with a product Each step is catalyzed by a specific enzyme © 2016 Pearson Education, Inc.

Catabolism Catabolism or Catabolic pathways: Release energy to produce ATP Break down complex molecules into simpler compounds E.g. cellular respiration; hydrolysis © 2016 Pearson Education, Inc. 5

Anabolism Anabolism or Anabolic pathways: Need energy from ATP and then store it Build complex molecules from simpler ones E.g. Photosynthesis; synthesis of polymers Bioenergetics is the study of how energy flows through living organisms © 2016 Pearson Education, Inc. 6

Energy of a System Potential Energy Energy: ability to do work (the capacity to cause change) In the case of living cells, work is the continuation of life itself Kinetic Energy “energy of motion”; doing the work Heat…..KE of molecules Light….KE from sun Potential Energy “energy of position”; stored energy Chemical….PE held in the bonds of molecules © 2016 Pearson Education, Inc. 7

A diver has more potential energy on the platform. Diving converts Figure 6.2 A diver has more potential energy on the platform. Diving converts potential energy to kinetic energy. Figure 6.2 Transformations between potential and kinetic energy Climbing up converts the kinetic energy of muscle movement to potential energy. A diver has less potential energy in the water. © 2016 Pearson Education, Inc.

First Law of Thermodynamics Thermodynamics: the study of energy transformations In an open system, energy and matter can be transferred between the system and its surroundings Organisms are open systems According to the first law of thermodynamics, the energy of the universe is constant Energy can be transferred and or transformed, but it cannot be created or destroyed The first law is also called the principle of conservation of energy © 2016 Pearson Education, Inc. 9

Energy of the universe is constant Figure 6.3 Energy of the universe is constant Every transformation increases entropy Heat CO2 H2O Chemical energy Figure 6.3 The two laws of thermodynamics (a) First law of thermodynamics (b) Second law of thermodynamics Bear converts chemical PE of fish into KE of running As the bear runs, he releases heat, which is adding to the disorder of the universe © 2016 Pearson Education, Inc.

The Second Law of Thermodynamics During every energy transfer or transformation, some energy is lost as heat According to the second law of thermodynamics Every energy transfer or transformation increases the entropy of the universe Entropy is a measure of disorder, or randomness © 2016 Pearson Education, Inc. 11

Combining 1st and 2nd Laws of Thermodynamics The quantity of energy in the universe is constant, but its quality is not Heat is given off as junk; heat is the lowest grade of energy Spontaneous processes occur without energy input; they can happen quickly or slowly For a process to occur spontaneously, it must increase the entropy of the universe © 2016 Pearson Education, Inc. 12

Biological Order and Disorder Cells create ordered structures from less ordered materials The evolution of more complex organisms does not violate the second law of thermodynamics Entropy (disorder) may decrease in a system, but the universe’s total entropy increases Conclusion: Organisms are islands of low entropy in an increasingly random universe © 2016 Pearson Education, Inc. 13

Figure 6.4 Order is evident in organisms. As open systems, organisms can increase their order as long as the order of their surroundings decreases. Figure 6.4 Order as a characteristic of life © 2016 Pearson Education, Inc.

Concept 6.2: The free-energy change of a reaction tells us whether or not the reaction occurs spontaneously Free energy: amount of energy available to do work; useable energy G = Gibbs Free Energy; G + H – TS Where H = enthalpy = total energy T = absolute temperature S = entropy Therefore, G = enthalpy minus energy lost to entropy ΔG = ΔH – TΔS Where ΔG = G product – G reactant Only processes with a negative ∆G are spontaneous Spontaneous processes can be harnessed to perform work © 2016 Pearson Education, Inc. 15

• More free energy (higher G) • Less stable • Greater work capacity Figure 6.5 • More free energy (higher G) • Less stable • Greater work capacity In a spontaneous change • The free energy of the system decreases (DG < 0) • The system becomes more stable • The released free energy can be harnessed to do work Figure 6.5 The relationship of free energy to stability, work capacity, and spontaneous change • Less free energy (lower G) • More stable • Less work capacity (a) Gravitational motion (b) Diffusion (c) Chemical reaction © 2016 Pearson Education, Inc.

Spontaneous; pushes from reactant to product; no energy required A + B ------<-- C Reactants Products Many chemical reactions are reversible Direction is influenced by [reactants] & [product] If G reactants = 10 (doing most of the work); G product = 2 ΔG = G product – G reactant ΔG = 2 – 10 ΔG Spontaneous; pushes from reactant to product; no energy required © 2016 Pearson Education, Inc. 17

+ Δ G A + B <------>----- C Reactants Products If G reactants = 1; G product = 5 (doing most of the work) ΔG = G product – G reactant ΔG = 5 – 1 + ΔG Non-spontaneous; pushes from product to reactants; energy required © 2016 Pearson Education, Inc.

Δ G = 0 A + B <------- C If G reactants = 7; G product = 7 Reactants Products If G reactants = 7; G product = 7 ΔG = G product – G reactant ΔG = 0 No work is done; the cell dies © 2016 Pearson Education, Inc.

Exergonic and Endergonic Reactions in Metabolism Exergonic Reactions: reactions that proceed spontaneously; - ΔG; releases energy; similar to catabolism Endergonic Reactions: reactions that require energy; not spontaneous; + ΔG; similar to anabolism © 2016 Pearson Education, Inc. 20

(a) Exergonic reaction: energy released, spontaneous Figure 6.6 (a) Exergonic reaction: energy released, spontaneous Reactants Amount of energy released (DG < 0) Free energy Energy Products Progress of the reaction (b) Endergonic reaction: energy required, nonspontaneous Products Figure 6.6 Free energy changes (∆G) in exergonic and endergonic reactions Amount of energy required (DG > 0) Free energy Energy Reactants Progress of the reaction © 2016 Pearson Education, Inc.

Concept 6.3: ATP powers cellular work by coupling exergonic reactions to endergonic reactions A cell does 3 main kinds of work Chemical Transport Mechanical To do work, cells do energy coupling: Use an exergonic process to power an endergonic one Most energy coupling in cells is mediated by ATP © 2016 Pearson Education, Inc. 22

(a) The structure of ATP Figure 6.8-1 ATP (adenosine triphosphate) composed of : adenine (a nitrogenous base) ribose (a sugar), 3 phosphate groups Adenine Triphosphate group (3 phosphate groups) Ribose Figure 6.8-1 The structure and hydrolysis of adenosine triphosphate (ATP) (part 1: structure) (a) The structure of ATP © 2016 Pearson Education, Inc.

Unstable P P P Adenosine triphosphate (ATP) H2O P P P Energy Inorganic Figure 6.8-2 Unstable P P P Adenosine triphosphate (ATP) H2O Figure 6.8-2 The structure and hydrolysis of adenosine triphosphate (ATP) (part 2: hydrolysis) P P P Energy i Inorganic Adenosine diphosphate (ADP) phosphate (b) The hydrolysis of ATP: releases energy © 2016 Pearson Education, Inc.

How Does ATP Do Work? Called Pi Transfer H20 hydrolyzes the last unstable P04 bond of ATP Releases ADP and P04 (also Pi) + energy Pi is given to an intermediate that needs to do work The phosphorylated intermediate is now very reactive and does the endergonic work The work is done and Pi comes off; now have product + ADP + Pi ATP then needs to be regenerated by the cell Cellular respiration regenerates the ATP by putting Pi back onto ADP Called Pi Transfer © 2016 Pearson Education, Inc. 25

Nonspontaneous DGGlu = +3.4 kcal/mol Glutamic acid Ammonia Glutamine Figure 6.9-1 NH3 NH2 DGGlu = +3.4 kcal/mol Glu Glu Glutamic acid Ammonia Glutamine Nonspontaneous (a) Glutamic acid conversion to glutamine Figure 6.9-1 How ATP drives chemical work: energy coupling using ATP hydrolysis (part 1: a nonspontaneous reaction) © 2016 Pearson Education, Inc.

Phosphorylated intermediate Phosphorylated intermediate Figure 6.9-2 P ADP ATP Glu Glu Glutamic acid Phosphorylated intermediate NH3 P ADP NH2 ADP P i Glu Glu Figure 6.9-2 How ATP drives chemical work: energy coupling using ATP hydrolysis (part 2: phosphorylation) Phosphorylated intermediate Glutamine (b) Conversion reaction coupled with ATP hydrolysis © 2016 Pearson Education, Inc.

(c) Free-energy change for coupled reaction Figure 6.9-3 DGGlu = +3.4 kcal/mol NH3 NH2 ATP ADP P Glu Glu i DGGlu = +3.4 kcal/mol DGATP = 7.3 kcal/mol + DGATP = 7.3 kcal/mol Figure 6.9-3 How ATP drives chemical work: energy coupling using ATP hydrolysis (part 3: coupled free energy change) Net DG = 3.9 kcal/mol (c) Free-energy change for coupled reaction © 2016 Pearson Education, Inc.

(a) Transport work: ATP phosphorylates transport proteins. Figure 6.10 Transport protein Solute ATP ADP P i P P i Solute transported (a) Transport work: ATP phosphorylates transport proteins. Vesicle Cytoskeletal track Figure 6.10 How ATP drives transport and mechanical work ATP ADP P ATP i Motor protein Protein and vesicle moved (b) Mechanical work: ATP binds noncovalently to motor proteins and then is hydrolyzed. © 2016 Pearson Education, Inc.

catabolism (exergonic, energy-releasing processes) Energy for cellular Figure 6.11 ATP H2O Energy from catabolism (exergonic, energy-releasing processes) Energy for cellular work (endergonic, energy-consuming processes) Figure 6.11 The ATP cycle ADP P i © 2016 Pearson Education, Inc.

Concept 6.4: Enzymes speed up metabolic reactions by lowering energy barriers Catalyst: a chemical agent that speeds up a reaction without being consumed by the reaction Enzyme: a biological catalyst Usually a protein Enzymes speed up reactions By lowering energy of activation: EA They do NOT change the nature of the reaction Enzymes are necessary for every reaction in your body © 2016 Pearson Education, Inc. 31

(C12H22O11) (C6H12O6) (C6H12O6) Sucrase + H2O + O H O OH Sucrose Figure 6.UN02 Sucrase + H2O + O H O OH Sucrose (C12H22O11) Glucose (C6H12O6) Fructose (C6H12O6) Figure 6.UN02 In-text figure, sucrose hydrolysis, p. 131 © 2016 Pearson Education, Inc.

Energy of Activation A B C D Transition state A B Free energy E C D Figure 6.12 A B C D Transition state A B Free energy E Energy of Activation A C D Reactants A B Figure 6.12 Energy profile of an exergonic reaction DG < 0 C D Products Progress of the reaction © 2016 Pearson Education, Inc.

Progress of the reaction Figure 6.13 Course of reaction without enzyme EA without enzyme EA with enzyme is lower Reactants Free energy Course of reaction with enzyme DG is unaffected by enzyme Figure 6.13 The effect of an enzyme on activation energy Products Progress of the reaction © 2016 Pearson Education, Inc.

Substrate Specificity of Enzymes Enzymes are very specific for the reactions they catalyze Substrate: the reactant that an enzyme acts on Enzyme-Substrate Complex: formed when the enzyme binds to its substrate Active site: the region on the enzyme where the substrate binds Induced fit of the enzyme to the substrate: brings chemical groups of the active site together © 2016 Pearson Education, Inc. 35

Substrate Active site Enzyme Enzyme-substrate complex Figure 6.14 Figure 6.14 Induced fit between an enzyme and its substrate Enzyme Enzyme-substrate complex © 2016 Pearson Education, Inc.

Substrates enter Substrates are active site. held in active site by Figure 6.15-s4 Substrates enter active site. Substrates are held in active site by weak interactions. Substrates Enzyme-substrate complex Active site is available for new substrates. Figure 6.15-s4 The active site and catalytic cycle of an enzyme (step 4) Enzyme Products are released. Substrates are converted to products. Products © 2016 Pearson Education, Inc.

Figure 6.16 Each enzyme has an optimal temperature and pH at which its reaction rate is the greatest Optimal temperature for typical human enzyme (37C) Optimal temperature for enzyme of thermophilic (heat-loving) bacteria (75C) Rate of reaction 20 40 60 80 100 120 Temperature (C) (a) Optimal temperature for two enzymes Optimal pH for pepsin (stomach enzyme) Optimal pH for trypsin (intestinal enzyme) Figure 6.16 Environmental factors affecting enzyme activity Rate of reaction 1 2 3 4 5 6 7 8 9 10 pH (b) Optimal pH for two enzymes © 2016 Pearson Education, Inc.

Cofactors Cofactors are nonprotein enzyme helpers Cofactors may be inorganic (such as a metal in ionic form) or organic An organic cofactor is called a coenzyme Most vitamins act as coenzymes or as the raw materials from which coenzymes are made © 2016 Pearson Education, Inc. 39

Enzyme Inhibitors Competitive inhibitors: mimics the substrate; blocks the active site of an enzyme E.g. Benadryl blocks histamine sites Tamiflu; anticancer drugs; cyanide Noncompetitive inhibitors: binds to another part of an enzyme, causing the enzyme to change shape and making the active site less effective E.g. sarin gas….nerve gas used by terrorists in Tokyo subway Penicillin; strychnine Examples of inhibitors include toxins, poisons, pesticides, and antibiotics © 2016 Pearson Education, Inc. 40

(b) Competitive inhibition (c) Noncompetitive inhibition Figure 6.17 (a) Normal binding (b) Competitive inhibition (c) Noncompetitive inhibition Substrate Active site Competitive inhibitor Enzyme Figure 6.17 Inhibition of enzyme activity Noncompetitive inhibitor © 2016 Pearson Education, Inc.