Chapter 6 – An Introduction to Metabolism

-Metabolism, Energy, and Life

-Enzymes

-Control of Metabolism

Metabolism

Metabolism is the totality of an organisms chemical reactions: • Includes all processes that involve breaking

down energy sources• Ex. cellular respiration, digestion, etc.

Arises from interactions between molecules and cellular environments.

Is concerned with managing the material and energy resources of the cell.

Metabolic Pathways

Are intricate and numerous. Utilize steps to minimize loss of energy

(most efficient paths are used). Are selectively accelerated by presence

of enzymes (biological catalysts).

Figure 6.1  The Complexity of Metabolism

Dots represent molecules

Lines represent chemical reactions that transform those molecules

Inset shows first two steps of glucose breakdown

Diagram represents a few hundred of the thousands of metabolic reactions that occur in a cell.

Two Types of Metabolic Pathways:

1. Catabolic – degradative processes, where complex molecules are broken down into simpler compounds and energy is released.

Ex. Cellular respiration

1. Anabolic – consume energy to build complicated molecules from simpler ones.

Ex. Protein synthesis

• these pathways intersect in such a way that the energy released from Catabolic can be used to drive Anabolic

• this transfer of energy is called Energy Coupling

Energy & Bioenergetics

Defined as capacity to do work (move matter against opposing forces).

Exists in a variety of forms, and work of life depends on ability of cells to transform energy from one type into another.

Bioenergetics is the study of how organisms manage their energy resources.

Potential vs. Kinetic vs. Activation

Potential Energy: stored energy that matter possesses because of its location or structure• Ex. Chemical energy in organic molecules, water

in reservoir behind dam Kinetic Energy: energy of motion

• Ex. Water gushing through dam, light energy, heat energy

Activation Energy: energy required to start a chemical reaction.

Figure 6.2x1 Kinetic and Potential Energy: Dam

Activation Energy

Activation energy converts potential energy to kinetic energy – the “push” to get a reaction started…• Ex. Boulder on top of hill, give a push to start

-OR-• Boulder on top of hill, use a lever to get

boulder rolling

Energy Transformations are Subject to Laws of Thermodynamics

Thermodynamics: study of the energy transformations that occur in a collection of matter

Scientists use terms system and surroundings to describe – • system is the matter under study • surroundings are everything outside of the system

Closed vs. Open Systems… closed systems are isolated from surroundings, and in open systems, energy can be transferred between the system and its surroundings

First Law of Thermodynamics

Energy can be transferred and transformed, but it cannot be created or destroyed.• Known as Principle of Conservation of Energy

Energy of universe is constant!

Second Law of Thermodynamics

Every energy transfer or transformation makes the universe more disordered:• ENTROPY – measure of disorder or

randomness.

• The more random a collection of matter, the greater its entropy.

So, restate as • Every energy transfer or transformation

increases the entropy of the universe.

Free Energy The portion of a system’s energy that can

perform work when temperature is uniform throughout the system.• Systems that are rich in energy are unstable.• Systems that are highly ordered are unstable.• In any spontaneous process, the free energy of a

system decreases. Organisms can live only at the expense of free

energy acquired from the surroundings.

Free energy: portion of a system’s energy that can perform work when temperature is uniform throughout the system…Is “free” because is available for work, not because it does not cost the

universe something!

See page 91 in textbook….

Scientists use free energy as a standard for measuring the spontaneity of a system alone.

ΔG = ΔH - T ΔS

G system’s quantity of free energy H system’s total energy T absolute temperature in Kelvin S system’s total entropy

• So, for a process to occur spontaneously, the system must either give up energy (decrease H), give up order (increase S), or both. The change in G must be negative.

• In other words, nature runs downhill in the sense of a loss of useful energy – the capacity to perform work.

Equilibrium

State of maximum stability.• In chemical reactions, as the reaction

proceeds toward equilibrium, the free energy of the mixture of reactants and products decreases.

Free energy increases when a reaction is pushed away from equilibrium.• A chemical reaction or physical process at

equilibrium performs no work.

Exergonic & Endergonic Reactions

Classification of reactions is based on the free-energy changes:• Exergonic – energy outward; proceed with a

net release of free energy -- usually releases energy in form of heat; these reactions occur spontaneously:• (Δ G is negative)

• Endergonic – energy inward; absorbs free energy from its surroundings, containers for these reactions tend to feel cool:• (Δ G is positive)

Figure 6.6  Energy Changes in Exergonic and Endergonic Reactions

Exergonic Reaction: ΔG < 0

Reaction proceeds with a net RELEASE of free energy…these reactions occur spontaneously.

Endergonic Reaction: ΔG > 0

Reaction proceeds with an ABSORPTION of free energy…these reactions are not spontaneous.

Metabolic Disequilibrium

Reactions in a closed system eventually reach equilibrium and can do no work.• Because systems at equilibrium have a ΔG of zero

and can do no work, a cell that has reached metabolic equilibrium is dead.

Thus, metabolic disequilibrium is a defining feature of life!

See pages 93 and 94 in textbook for open vs. closed system

Figure 6.7 Disequilibrium and Work in Closed and Open Systems

ATP and Energy Coupling

3 kinds of work in cell:1. mechanical2. transport3. chemical

Energy Coupling: use of an exergonic process to drive and endergonic process.

ATP mediates most energy coupling in cells!

Figure 6.8 The Structure and Hydrolysis of ATP

When bonds are broken from ATP to ADP (hydrolysis),

7.3 kcal/mol of energy is released – is exergonic

All are negatively charged – crowded and repel, creating instability!

Phosphorylation

Recipient of phosphate group when ATP loses it.

This phosphorylated intermediate is more reactive (less stable) than the original molecule.

Nearly all cellular work depends on ATP’s energizing of other molecules by transferring phosphate groups.

Figure 6.10 The ATP Cycle

ATP is a renewable resource that can be regenerated…

Is fast – working muscle cell recycles its entire ATP pool once each minute; Turnover represents 10 million molecules of ATP generated per second in a cell.

ENERGY COUPLING: The use of exergonic processes to drive endergonic processes.

Enzymes http://www.sumanasinc.com/webcontent/animations/content/en

zymes/enzymes.html

Catalysts are chemical agents that change the rate of reaction without being consumed by the reaction.

Enzymes are catalytic proteins.• Enzymes keep chemical traffic through the

pathways of metabolism from getting too congested and bogged down.

Figure 6.11 Example of an enzyme-catalyzed reaction: Hydrolysis of sucrose

A solution of sucrose dissolved in sterile water will sit for years at room temp with no appreciable hydrolysis occurring….BUT, if add SUCRASE (an enzyme), the sucrose will be converted in seconds…

Figure 6.12 Energy profile of an exergonic reaction

Uphill - Reactants A & B must absorb enough energy from the surroundings to surmount the hill of activation energy and reach the unstable transition state.

Downhill – Bonds break, and new bonds form. Energy is released to surroundings during this process (EXERGONIC - ∆G negative) – products have less energy than reactants.

THIS IS WITH NO ENZYME ACTIVITY!!!

Figure 6.13 Enzymes lower the barrier of activation energy

Without affecting the free-energy change (∆G) for the reaction, an enzyme speeds the reaction up by lowering the activation energy required to start the reaction.

Black Curve – shows course of reaction w/out enzyme.

Red Curve – shows course of reaction with enzyme.

Enzymes

Read 1st & 2nd paragraph on page 97 under Enzymes and Activation Energy…

• AN ENZYME SPEEDS A REACTION BY LOWERING THE ACTIVATION ENERGY REQUIRED TO START THE REACTION.

• Cannot change the ΔG for a reaction.

• Cannot make an endergonic reaction exergonic.

• Can only hasten reactions that would occur normally, regardless!

• Enzymes ARE NOT USED UP during the course of the reaction!

Enzymes The reactant an enzyme acts on is its substrate.

• Enzymes are substrate specific, and can distinguish its substrate from even closely related isomers!

Each enzyme has an active site – the catalytic center of the enzyme!

Rate of conversion of substrate into new products depends on initial concentration of substrate!

But there is a limit to total speed of reaction – all enzyme molecules may be working (saturated), so only way to increase reaction speed is to ADD MORE ENZYME!• So…to speed up reaction…add MORE substrate or add more

enzyme!!!

Figure 6.14 The induced fit between an enzyme and its substrate

The specificity of an enzyme is attributed to a compatible fit between the shape of its active site and the shape of the substrate.

Active site of enzyme can be seen in computer model as groove on surface of protein (blue)

On entering the active site, the substrate (red) induces a change in the shape of the protein that causes the active site to embrace the substrate.

Figure 6.15 The Catalytic Cycle of an Enzyme

Substrates enters active site & binds to

protein enzyme – enzyme changes shape to embrace

substrate (induced-fit)

Physical and Chemical Environment Affects Enzyme Activity…

Temperature – too high, denatures protein pH – too high or too low, denatures protein Cofactors – inorganic nonprotein helper bound

to active site; must be present for some enzymes to function (zinc, iron, copper)

Coenzymes – organic nonprotein helper bound to active site; again, must be present (vitamins)

http://www.sumanasinc.com/webcontent/animations/content/proteinstructure.html

Inhibitors

Enzyme Inhibitors – stop enzyme from working!• 2 types – competitive and noncompetitive

• Competitive blocks active site, mimics substrate

• Noncompetitive bind to another part of enzyme and change shape of enzyme – so can’t work on substrate

• http://bcs.whfreeman.com/thelifewire/content/chp06/0602001.html

Figure 6.17 Inhibition of Enzyme Activity

Mimics the substrate and competes for the active site.

Binds to the enzyme at a location away from the active site, but alters the shape of the enzyme so that the active site is no longer fully functional.

Control of Metabolism

Cell regulates metabolic pathways by controlling when and where enzymes are active.

Does this by :• switching on or off the genes for production of

specific enzymes-OR-

• regulating enzymes once made

Figure 6.18 Allosteric regulation of enzyme activity

*By binding to allosteric site, can either inhibit or stimulate

*Most allosterically regulated enzymes are made up of one or more polypeptide subunits – each having its own active site.

Figure 6.19 Feedback inhibition

Feedback Inhibition:

Switching off of a metabolic pathway by its end product, which acts an inhibitor of an enzyme within the pathway.

Figure 6.20 Cooperativity

Similar to allosteric activation – amplifies the response of enzymes to substrates: One substrate molecule primes an enzyme to accept more substrate molecules…