Metabolism Chapter 8. I. Thermodynamics Metabolism All the chemical reactions in an organism.

Metabolism

Chapter 8

I. Thermodynamics

Metabolism

• All the chemical reactions in an organism

Catabolic pathways

• Break down complex molecules into simpler molecules– Releases energy– Examples?• Digestive enzymes break down food to release energy

Anabolic pathway

• Build complex molecules from simple molecules– Consume energy– Example: Body links amino acids to form muscle in

response to exercise

Energy

• The ability to do work

Kinetic energy

• Energy of movement

Potential energy

• Stored energy as a result of position or structure– Chemical energy – form of potential energy stored

in molecules. On the platform, a diverhas more potential energy.

Diving converts potentialenergy to kinetic energy.

Climbing up converts kineticenergy of muscle movement to potential energy.

In the water, a diver has less potential energy.

Figure 8.2

• 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)

Chemicalenergy

Thermodynamics

• Study of energy transformation in matter• First law: energy cannot be created or

destroyed, only transferred or transformed• 2nd law: Energy that is transferred or

transformed increases entropy or the amount of disorder or randomness in the universe

The Second Law of Thermodynamics

Figure 8.3

Second law of thermodynamics: Every energy transfer or transformation increasesthe disorder (entropy) of the universe. For example, disorder is added to the cheetah’ssurroundings in the form of heat and the small molecules that are the by-productsof metabolism.

(b)

Heat co2

H2O+

II. Free energy

III. ATP

Figure 8.8

O O O O CH2

H

OH OH

H

N

H H

ON C

HC

N CC

N

NH2Adenine

RibosePhosphate groups

O

O O

O

O

O

-

- - -

CH

Energy coupling

• Use of exergonic process to drive an endergonic one

ATP

• Primary source of energy for coupling– Made up of adenine bound to ribose and three

phosphate groups– When ATP is hydrolyzed energy is released in an

endergonic reation

Figure 8.9

P

Adenosine triphosphate (ATP)

H2O

+ Energy

Inorganic phosphate Adenosine diphosphate (ADP)

PP

P PP i

• Energy is released from ATP– When the terminal phosphate bond is broken

• ATP drives endergonic reactions– By phosphorylation,

transferring a phosphate to other molecules

ADP• When ATP is hydrolyzed it become ADP– How many phophates does ADP have?

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 yieldingprocesses)

ATP hydrolysis to ADP + P i yields energy

Figure 8.12

IV. Enzymes

Catalyst

• Changes the rate of a chemical reaction without being altered in the process

Enzymes

• Macromolecules that are biological catalysts– Considered proteins

Activation energy

• Amount of energy it takes to start a reaction, or the amount of energy it takes to break the bonds of reactant molecules– Enzymes speed up reactions by LOWERING

activation energy

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

Figure 8.15

Exergonic reaction – energy released

Endergonic reaction – energy required

Parts of enzymes

• Substrate: enzyme reactants• Active sites: site where substrate binds• Enzyme substrate complex: formed when the

substrate and enzyme bind– After substrate binds it is converted into products

which are released from the enzyme

Figure 8.16

Substate

Active site

Enzyme

(a)

• Induced fit of a substrate– Brings chemical groups of the active site into

positions that enhance their ability to catalyze the chemical reaction

Figure 8.16 (b)

Enzyme- substratecomplex

• 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 (and R groups ofits amino acids) can lower EA

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 intoProducts.

5 Products areReleased.

6 Active siteIs available fortwo new substrateMole.

Figure 8.17

Enzyme activity

• Activity of an enzyme can be affected by several factors:– Changes in• Temperature• pH

• Changes in temperature and pH can change the shape of the enzyme, making it less effective

Cofactors

• Non-protein helpers– Include metals like zinc, iron and copper– Function to allow catalysis to occur

Coenzymes

• Organic cofactors such as vitamins

Competitive inhibitors• Reversible inhibitors that compete with the

substrate for the active site– Very similar to normal substrate

Figure 8.19 (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

Noncompetitive inhibitors

• Prevent enzyme activity by binding to anotehr part of the enzyme– Cause change in shape

Figure 8.19

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

V. Enzyme activity regulation

Allosteric site

• Specific binding site other than the active site where regulators bind and change the shape of the enzyme. – Can either stimulate OR inhibit the activity

Stabilized inactiveform

Allosteric activaterstabilizes active fromAllosteric enyzme

with four subunitsActive site(one of four)

Regulatorysite (oneof four)

Active formActivator

Stabilized active form

Allosteric activaterstabilizes active 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

Figure 8.20

Feedback inhibition

• The end product of an enzymatic pathway can switch off the pathway by binding to the allosteric site (the result!)– Increases efficiency of pathway by turning off

when the end product accumulates in the cell.

• Feedback inhibition

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)

Figure 8.21