Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Chapter 8

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Overview: The Energy of Life The living cell – Is a miniature factory where thousands of reactions occur – Converts energy in many ways

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Concept 8.1 Metabolism – Is the totality of an organism’s chemical reactions – Arises from interactions between molecules

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Organization of the Chemistry of Life into Metabolic Pathways A metabolic pathway has many steps – Begins with a specific molecule and ends with a product – Each are catalyzed by a specific enzyme at each step Enzyme 1Enzyme 2Enzyme 3 A B C D Reaction 1Reaction 2Reaction 3 Starting molecule Product

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Two types of pathways: 1) Catabolic pathways – Break down complex molecules into simpler compounds – Release energy – Results in lower energy products

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 2) Anabolic pathways – Build complicated molecules from simpler ones – Consume energy – Results in high energy products

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Forms of Energy Energy – Is the capacity to cause change – Exists in various forms, of which some can perform work

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Kinetic energy – Energy associated with motion Potential energy – Energy stored in the location of matter – Includes chemical energy stored in molecular structure

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Energy can be converted – From one form to another On the platform, a diver has more potential energy. Diving converts potential energy to kinetic energy. Climbing up converts kinetic energy of muscle movement to potential energy. In the water, a diver has less potential energy. Figure 8.2

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings The Laws of Energy Transformation Thermodynamics – Is the study of energy transformations

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings The First Law of Thermodynamics According to the first law of thermodynamics – Energy can be transferred and transformed – Energy cannot be created or destroyed

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings An example of energy conversion Figure 8.3 First law of thermodynamics: Energy can be transferred or transformed but Neither created nor destroyed. For example, the chemical (potential) energy in food will be converted to the kinetic energy of the cheetah’s movement in (b). (a) Chemical energy

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Each time energy is convert, some becomes unusable (not able to do work) – Usually in the form of heat

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings The Second Law of Thermodynamics According to the second law of thermodynamics – Spontaneous changes that do not require outside energy increase the entropy, or disorder, of the universe In other words, each time energy is converted, it is not a perfect conversion. We do not get 100% of the potential energy converted into kinetic energy. The energy isn’t lost or destroyed, just unavailable for work.

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings What!?! If you remember: 1)Energy isn’t created or destroyed, just converted from one form to another 2)Every time it is converted, the conversion isn’t 100% efficient

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Concept 8.2 Chemical reactions in metabolism can be either exergonic or endergonic Some terms to know: – Free energy – portion of system’s energy that can do work – Spontaneous reaction – reaction that occurs without the input of energy

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Exergonic and Endergonic Reactions in Metabolism An exergonic reaction – Proceeds with a net release of free energy and is spontaneous Figure 8.6 Reactants Products Energy Progress of the reaction Amount of energy released (∆G <0) Free energy (a) Exergonic reaction: energy released

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings An endergonic reaction – Is one that absorbs free energy from its surroundings and is nonspontaneous Figure 8.6 Energy Products Amount of energy released (∆G>0) Reactants Progress of the reaction Free energy (b) Endergonic reaction: energy required

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings In the body, exergonic reactions and endergonic reactions are coupled The products of one, become the reactants of the other – This prevents cells from reaching equilibrium and helps to maintain life

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Concept 8.3 ATP powers cellular work by coupling exergonic reactions to endergonic reactions A cell does three main kinds of work – Mechanical – Transport – Chemical

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Energy coupling – Is a key feature in the way cells manage their energy resources to do this work

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings The Structure and Hydrolysis of ATP ATP (adenosine triphosphate) – Is the cell’s energy shuttle – Provides energy for cellular functions Figure 8.8 O O O O CH 2 H OH H N HH O N C HC N C C N NH 2 Adenine Ribose Phosphate groups O O O O O O CH

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Energy is released from ATP – When the terminal phosphate bond is broken Figure 8.9 P Adenosine triphosphate (ATP) H2OH2O + Energy Inorganic phosphate Adenosine diphosphate (ADP) PP PPP i

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings How ATP Performs Work ATP drives endergonic reactions – By phosphorylation, transferring a phosphate to other molecules that changes and then does work

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings The Regeneration of ATP Catabolic pathways – Drive the regeneration of ATP from ADP and phosphate ATP synthesis from ADP + P i requires energy ATP ADP + P i Energy for cellular work (endergonic, energy- consuming processes) Energy from catabolism (exergonic, energy yielding processes) ATP hydrolysis to ADP + P i yields energy Figure 8.12

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Concept 8.4 Enzymes speed up metabolic reactions by lowering energy barriers A catalyst – Is a chemical agent that speeds up a reaction without being consumed or changed by the reaction An enzyme – Is a catalytic protein

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings The Activation Barrier Every chemical reaction between molecules – Involves both bond breaking and bond forming – In order to do this, the energy of activation must be overcome

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings The activation energy, E A – Is the initial amount of energy needed to start a chemical reaction – Is often supplied in the form of heat from the surroundings in a system

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings The energy profile for an exergonic reaction Free energy Progress of the reaction ∆G < O EAEA Figure 8.14 A B C D Reactants A C D B Transition state A B CD Products

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings How Enzymes Lower the E A Barrier An enzyme catalyzes reactions – By lowering the E A barrier

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings The effect of enzymes on reaction rate Progress of the reaction Products Course of reaction without enzyme Reactants Course of reaction with enzyme EAEA without enzyme E A with enzyme is lower ∆G is unaffected by enzyme Free energy Figure 8.15

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Substrate Specificity of Enzymes The substrate – Is the reactant an enzyme acts on The enzyme – Binds to its substrate, forming an enzyme- substrate complex

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings The active site – Is the region on the enzyme where the substrate binds Figure 8.16 Substate Active site Enzyme (a)

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Catalysis in the Enzyme’s Active Site In an enzymatic reaction – The substrate binds to the active site

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings The catalytic cycle of an enzyme Substrates Products Enzyme Enzyme-substrate complex 1 Substrates enter active site; enzyme changes shape so its active site embraces the substrates (induced fit). 2 Substrates held in active site by weak interactions, such as hydrogen bonds and ionic bonds. 3 Active site (and R groups of its amino acids) can lower E A and speed up a reaction by acting as a template for substrate orientation, stressing the substrates and stabilizing the transition state, providing a favorable microenvironment, participating directly in the catalytic reaction. 4 Substrates are Converted into Products. 5 Products are Released. 6 Active site Is available for two new substrate Mole. Figure 8.17

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings The active site can lower an E A barrier by – Orienting substrates correctly – Straining substrate bonds – Providing a favorable microenvironment – Covalently bonding to the substrate

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Effects of Local Conditions on Enzyme Activity The activity of an enzyme – Is affected by general environmental factors: Temperature pH level – Presence of “helper” molecules

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Enzymes affected by: Each enzyme – Has an optimal temperature in which it can function best – Has an optimal pH in which it can function best

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Enzyme Helpers Cofactors – Are nonprotein enzyme helpers – Inorganic Examples: zinc, iron, copper Coenzymes – Are organic cofactors Examples: most vitamins

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Enzyme Inhibitors Inhibitors – selectively slow or stop specific enzymes May be poisons May be naturally occurring regulators in the body

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Enzyme Inhibitors (Type 1) Competitive inhibitors – Bind to the active site of an enzyme, competing with the substrate Figure 8.19 (b) Competitive inhibition A competitive inhibitor mimics the substrate, competing for the active site. Competitive inhibitor A substrate can bind normally to the active site of an enzyme. Substrate Active site Enzyme (a) Normal binding

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Enzyme Inhibitors (Type 2) Noncompetitive inhibitors – Bind to another part of an enzyme, changing the function Figure 8.19 A noncompetitive inhibitor binds to the enzyme away from the active site, altering the conformation of the enzyme so that its active site no longer functions. Noncompetitive inhibitor (c) Noncompetitive inhibition

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Binding of inhibitors can be permanent or reversible – Usually permanent if bound with covalent bonds – may be reversible if bound by weak bonds

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Concept 8.5 Regulation of enzyme activity helps control metabolism A cell’s metabolic pathways – Must be tightly regulated – May be sped up or slowed down

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Allosteric Regulation of Enzymes Allosteric regulation – Is when a protein’s function at one site is affected by binding of a regulatory molecule at another site Regulatory molecule may bind at regulatory site Or at active site

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Allosteric Regulation or Inhibition Stabilized inactive form Allosteric activater stabilizes active from Allosteric enyzme with four subunits Active site (one of four) Regulatory site (one of four) Active form Activator Stabilized active form Allosteric activater stabilizes active form Inhibitor Inactive form Non- functional active site (a) Allosteric activators and inhibitors. In the cell, activators and inhibitors dissociate when at low concentrations. The enzyme can then oscillate again. Oscillation Figure 8.20

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Allosteric Regulation and Amplification Cooperativity – Is a form of allosteric regulation that can amplify enzyme activity – By binding one active site, all active sites are locked into active conformation Substrate Inactive form Stabilized active form Figure 8.20

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Feedback Inhibition In feedback inhibition – The end product of a metabolic pathway shuts down the pathway – Another form of metabolic control Prevents wasting of chemical resources