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An Introduction to Metabolism

Chapter 8

• Objectives• Distinguish between the following pairs of terms:

catabolic and anabolic pathways; kinetic and potential energy; open and closed systems; exergonic and endergonic reactions.

• Explain the second law of thermodynamics and explain why it is not violated by living organisms.

• Explain in general terms how cells obtain the energy to do cellular work.

• Explain how ATP performs cellular work.• Describe the function of enzymes in biological systems.

• Explain why an investment of activation energy is necessary to initiate a spontaneous reaction.

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• Describe the mechanisms by which enzymes lower activation energy.

• Describe how allosteric regulators may inhibit or stimulate the activity of an enzyme.

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Introduction

• Characteristics of organisms are all the end-products of the chemical reactions that occur in their cells

• The living cell is a miniature factory where thousands of reactions occur – chemical reactions carried out for the purpose of

energy transformation– convert energy in many ways

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Organization of the Chemistry of Life into Metabolic Pathways

• An organism’s metabolism transforms matter and energy, subject to the laws of thermodynamics– metabolism is the totality of an organism’s

chemical reactions• arises from interactions between molecules

• A metabolic pathway has many steps that begin with a specific molecule and end with a product– each step is catalyzed by a specific enzyme

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• Catabolic pathways break down complex molecules into simpler compounds– release energy

• Anabolic pathways build complicated molecules from simpler ones– consume energy

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Energy – The Capacity to do Work

• Energy is described and measured by how it affects matter– Two types of energy:

• kinetic-energy of motion

• potential-stored capacity to do work– due to position of object with respect to a force field

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• Energy can be converted from one form to another– When an object in a force field moves with

respect to the source of the force, its potential energy changes

• movement towards the source decreases the potential energy, movement away increases the potential energy

• the movement of an object requires energy (kinetic energy); any excess energy can be used for other activities other than movement and is known as free energy

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Transformations between kinetic and potential energy

Laws of Energy Conservation

• Thermodynamics-study of energy transformations

• Two laws govern energy transformation:– First law (energy conservation)

• total amount of energy in universe is constant– can be transferred or transformed but cannot be created

or destroyed

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– Second law (entropy-disorder-increases)• every energy transformation increases entropy

– energy available for doing useful work decreases with every transformation

• order in organisms is maintained, or increased, at the expense of the entropy of the universe

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Energy and Living Things

• Organisms use free energy– free energy is the energy available to do work

• symbolized by “G”

• two components– system’s total energy – H– system’s entropy – S

• equation for calculating free energy– G = H – TS

» not all energy in a system is available to do work

• level of free energy is a measure of instability– the higher the free energy the greater the tendency to

change to a more stable state

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– systems that spontaneously change to a more stable state have high energy, low entropy or both

» in spontaneous processes, free energy decreases

• change in free energy (∆G) given by the following equation

– ∆G = Gfinal state – Gstarting state or– ∆G = ∆H - T ∆S

» for a spontaneous process to occur, system must give up energy, order, or both

• Nature runs downhill– loses useful energy

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The relationship of free energy to stability, work capacity, and spontaneous change

Free Energy and Metabolism

• Chemical reactions in cells either store or release energy– endergonic reactions require input of energy

• energy input equals difference in potential energy between reactants and products

– exergonic reactions release energy• energy released equals difference in potential energy

between reactants and products

– cellular metabolism is sum total of all endergonic and exergonic reactions in cells

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Equilibrium and Metabolism

• Reactions in a closed system eventually reach equilibrium– individual energy-releasing reactions continue

until they reach equilibrium• energy release ceases

– cells link energy-releasing reactions together in chains to maximize the release of energy

• results in a constant flow of materials in and out preventing metabolic pathways from reaching equilibrium

– continuous energy release as long as cell is alive

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ATP and Cellular Work

• A cell does three main kinds of work– mechanical– transport– chemical

• Energy coupling is a key feature in the way cells manage their energy resources to do this work

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• ATP is cell’s energy shuttle– most cell reactions require small amounts of

energy– food storage molecules contain large amounts of

energy– energy in food molecules is converted to energy

in ATP• one food molecule=many ATP (e.g. 1 x glucose=36

ATP)

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• Hydrolysis of ATP releases energy– terminal covalent bonds between outer phosphate

groups are energy rich and easily hydrolyzed– forms ADP and phosphate group

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• ATP hydrolysis can be coupled to other reactions– phosphate group used to phosphorylate other

molecules-energizing reaction

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How ATP Performs Work

• ATP drives endergonic reactions– By phosphorylation, transferring a phosphate to

other molecules

• Phosphorylation of a protein usually results in the protein changing shape– dephosphorylation (removal of the phosphate)

allows protein to return to original shape• phosphorylation-dephosphorylation cycle of proteins can

be used to perform tasks in cells

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• ATP can serve as the energy currency of cells because ATP can be regenerated from ADP and Pi (inorganic phosphate)– catabolic pathways drive the regeneration of ATP

from ADP and phosphate• endergonic reactions of cellular respiration linked to the

phosphorylation of ADP– reforms ATP

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Enzymes

• Every chemical reaction between molecules involves both bond breaking and bond forming

• Enzymes are large protein molecules that act as biological catalysts– a catalyst is a chemical agent that speeds up a

reaction without being consumed by the reaction• an enzyme is a catalytic protein

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The Activation Barrier

• Energy of activation (EA) is “energy barrier”, amount of energy needed to initiate a chemical reaction– it is often supplied in the form of heat from the

surroundings in a system

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• Enzymes lower energy barriers– reduce the energy of activation– do not change the ∆G of the reaction

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Substrate Specificity of Enzymes

• Specific enzymes catalyze each cell reaction– reactant=substrate– binds to enzyme active site

• forms an enzyme-substrate complex

– substrate converted to product– enzyme unchanged

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• Substrate interacts only with enzyme active site– pocket or groove on the surface of the enzyme

that is compatible with the shape of the substrate• entry of substrate into active site induces slight change

in shape– active site better fits around substrate– chemical groups lining active site repositioned to better

catalyze chemical reaction

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Catalysis in the Enzyme’s Active Site

• Active site is central to enzyme activity– binding of substrate forms enzyme-substrate

complex• several mechanisms used by enzyme to lower EA

– orienting substrates correctly– straining substrate bonds– providing a favorable microenvironment– covalently bonding to the substrate

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– catalytic cycle of enzyme occurs very rapidly• average is about 1,000 substrate molecules per second• rate partially determined by substrate concentration

– high initial substrate level → high reaction rate

• each enzyme has a saturating level of substrate– every enzyme molecule has its active site engaged– represents limiting rate of reaction

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• metabolic reactions are reversible– enzymes can catalyze both forward and backward

reactions» direction of reaction depends on concentrations of

substrates and products» enzymes catalyze reactions in direction of equilibrium

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Effects of Local Conditions on Enzyme Activity

• Factors that affect enzyme activity– temperature, pH, salt concentration, and

presence of cofactors and coenzymes• remember that an enzyme is a protein so anything that

denatures a protein affects an enzyme

– cofactors are non-protein enzyme helpers– coenzymes are organic cofactors

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Enzyme Inhibitors

– Inhibitors block enzyme action• competitive inhibitors-bind to active site• noncompetitive inhibitors-bind to second site (allosteric

site) on enzyme

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Enzyme Regulation

• Regulation of enzyme activity helps control metabolism– a cell’s metabolic pathways must be tightly

regulated

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• Allosteric regulation is the term used to describe any case in which a protein’s function at one site is affected by binding of a regulatory molecule at another site– many enzymes are allosterically regulated

• they change shape when regulatory molecules bind to specific sites, affecting function

• some enzymes are activated by an allosteric activator – converts inactive enzyme to active enzyme

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• Cooperativity is a form of allosteric regulation that can amplify enzyme activity– binding of substrate can increase binding of more

substrate in enzymes that have multiple active sites

• binding of first substrate molecule causes change in enzyme shape that favors binding of further substrate molecules.

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• Negative feedback-inhibition by product of reaction– binds to second binding site on enzyme known as

allosteric site– results in change of shape that converts enzyme

from active to inactive form

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• Within the cell, many enzymes are associated with specific regions of the cell– may be grouped into complexes– may be incorporated into membranes

• Some pesticides and antibiotics function by inhibiting enzymes

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