Energy and Metabolism

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Energy and Metabolism

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The Energy of Life • The living cell generates thousands of

different reactions• Metabolism

• Is the totality of an organism’s chemical reactions

• Arises from interactions between molecules

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

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Enzymes Lower the EA Barrier

Progress of the reaction

Products

Course of reaction without enzyme

Reactants

Course of reaction with enzyme

EA

withoutenzyme

EA with enzymeis lower

∆G is unaffected by enzymeFr

ee e

nerg

y

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Enzymes Are Biological Catalysts that…

• Are proteins that carry out most catalysis in living organisms.

• Are highly specific that can speed up only one or a few chemical reactions.

• Have unique three-dimensional shape that enables an enzyme to stabilize a temporary association between substrates.

• It is not changed or consumed in the reaction, only a small amount is needed, and can then be reused.

• By controlling which enzymes are made, a cell can control which reactions take place in the cell.

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Substrate Specificity of Enzymes• Almost all enzymes are globular proteins with one

or more active sites on their surface.• The substrate is the reactant an enzyme acts on• Reactants bind to the active site to form an

enzyme-substrate complex.• The 3-D shape of the active site and the substrates

must match, like a lock and keySubstate

Active site

Enzyme

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Substrate Specificity of Enzymes• Binding of the substrates causes the enzyme to

adjust its shape slightly, leading to a better induced fit.

• Induced fit of a substrate brings chemical groups of the active site into positions that enhance their ability to catalyze the chemical reaction

• When this happens, the substrates are brought close together and existing bonds are stressed. This reduces the amount of energy needed to reach the transition state.

Enzyme- substratecomplex

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The Catalytic Cycle Of An Enzyme

Substrates

Products

Enzyme

Enzyme-substratecomplex

1 Substrates enter active site; enzymechanges shape so its active siteembraces the substrates (induced fit).

2 Substrates held inactive site by weakinteractions, such ashydrogen bonds andionic bonds.

3 Active site can lower EA

and speed up a reaction by• acting as a template for substrate orientation,• stressing the substrate bonds 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 siteIs available fortwo new substrateMole.

Figure 8.17

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1 The substrate, sucrose, consistsof glucose and fructose bonded together.

Bond

Enzyme

Active site

The substrate binds to the enzyme, forming an enzyme-substrate complex.

2

H2O

The binding of the substrate and enzyme places stress on the glucose-fructose bond, and the bond breaks.

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Glucose Fructose

Products are released, and the enzyme is free to bind other substrates.

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The Catalytic Cycle Of An Enzyme

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Factors Affecting Enzyme Activity• Temperature - rate of an enzyme-catalyzed

reaction increases with temperature, but only up to an optimum temperature.

• pH - ionic interactions also hold enzymes together.

• Inhibitors and Activators

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Effects of Temperature and pH• Each enzyme has an optimal temperature in

which it can function

Optimal temperature for enzyme of thermophilic

Rat

e of

reac

tion

0 20 40 80 100Temperature (Cº)

(a) Optimal temperature for two enzymes

Optimal temperature fortypical human enzyme

(heat-tolerant) bacteria

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Effects of Temperature and pH• Each enzyme has an optimal pH in which

it can function

Figure 8.18

Rat

e of

reac

tion

(b) Optimal pH for two enzymes

Optimal pH for pepsin (stomach enzyme)

Optimal pHfor trypsin(intestinalenzyme)

10 2 3 4 5 6 7 8 9

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Factors Affecting Enzyme Activity• Inhibitor - substance that binds to an enzyme

and decreases its activity – feedback• Competitive inhibitors - compete with the

substrate for the same active site• Noncompetitive inhibitors - bind to the

enzyme in a location other than the active site

• Allosteric sites - specific binding sites acting as on/off switches

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Enzyme Inhibitors• Competitive inhibitors bind to the active site of an enzyme,

competing with the substrate

(b) Competitive inhibition

A competitiveinhibitor mimics the

substrate, competingfor the active site.

Competitiveinhibitor

A substrate canbind normally to the

active site of anenzyme.

Substrate

Active site

Enzyme

(a) Normal binding

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Enzyme Inhibitors• Noncompetitive inhibitors bind to another

part of an enzyme, changing the function

A noncompetitiveinhibitor binds to the

enzyme away fromthe active site, altering

the conformation ofthe enzyme so that its

active site no longerfunctions.

Noncompetitive inhibitor

(c) Noncompetitive inhibition

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Regulation Of Enzyme Activity Helps Control Metabolism

• Chemical chaos would result if a cell’s metabolic pathways were not tightly regulated

• To regulate metabolic pathways, the cell switches on or off the genes that encode specific enzymes

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Regulation Of Enzyme Activity Helps Control Metabolism

• 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

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

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The term allostery comes from the Greek allos, "other", and stereos, "solid (object)", in reference to the fact that the regulatory site of an allosteric protein is physically distinct from its active site.

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Allosteric Activation and Inhibition

• Most allosterically regulated enzymes are made from polypeptide subunits

• Each enzyme has an active and an inactive form

Allosteric ActivationThe binding of an activator stabilizes the active

form of the enzyme.

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Allosteric InhibitionThe binding of an inhibitor stabilizes the inactive form of the enzyme

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Stabilized inactiveform

Allosteric activaterstabilizes active from

Allosteric enyzmewith four subunits

Active site(one of four)

Regulatorysite (oneof four)

Active formActivator

Stabilized active form

Allosteric activaterstabilizes inactive form

InhibitorInactive formNon-functionalactivesite

(a) Allosteric activators and inhibitors. In the cell, activators and inhibitors dissociate when at low concentrations. The enzyme can then oscillate again.

Oscillation

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Cooperativity• Is a form of allosteric regulation that can amplify

enzyme activity

Binding of one substrate molecule toactive site of one subunit locks all subunits in active conformation.

Substrate

Inactive form Stabilized active form

(b) Cooperativity: another type of allosteric activation. Note that the inactive form shown on the left oscillates back and forth with the active form when the active form is not stabilized by substrate.

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Factors Affecting Enzyme Activity

• Activators - substances that bind to allosteric sites and keep the enzymes in their active configurations - increases enzyme activity• Cofactors - chemical components that

facilitate enzyme activity• Coenzymes - organic molecules that

function as cofactors

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Regulation of Biochemical Pathways

• Biochemical pathways must be coordinated and regulated to operate efficiently.

• Advantageous for cell to temporarily shut down biochemical pathways when their products are not needed

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Positive Feedback in Coagulation

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In Feedback Inhibition:• The end product of a

metabolic pathway shuts down the pathway

• When the cell produces increasing quantities of a particular product, it automatically inhibits its ability to produce more of the substance

Active siteavailable

Isoleucineused up bycell

Feedbackinhibition

Isoleucine binds to allosteric site

Active site of enzyme 1 no longer binds threonine;pathway is switched off

Initial substrate(threonine)

Threoninein active site

Enzyme 1(threoninedeaminase)

Intermediate A

Intermediate B

Intermediate C

Intermediate D

Enzyme 2

Enzyme 3

Enzyme 4

Enzyme 5

End product(isoleucine)

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Harmful Effects of Positive FeedbackPositive feedback can be harmful. Two specific

examples of these harmful outcomes would be:1. Fever can cause a positive feedback within

homeostasis that pushes the body temperature continually higher. If the temperature reaches 45 degrees centigrade (113 degrees Fahrenheit) cellular proteins denature bringing metabolism to a stop and death.

2. Chronic hypertension can favor the process of atherosclerosis which causes the openings of blood vessels to narrow. This, in turn, will intensify the hypertension and bring on more damage to the walls of blood vessels.

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• http://www.mhhe.com/biosci/esp/2002_general/Esp/folder_structure/tr/m1/s7/trm1s7_3.htm

• http://www.hopkinsmedicine.org/hematology/Coagulation.swf

• http://www.youtube.com/watch?v=hb92wr93JrE