Enzymes. Enzyme: a macromolecule (usually a protein) that acts as a catalyst; a chemical agent that...

Enzymes

• Enzyme: a macromolecule (usually a protein) that acts as a catalyst; a chemical agent that speeds up a reaction without being consumed (used up) in the reaction.

• Every chemical reaction between molecules involves breaking some bonds and creating others.

• To reach a point where bonds can be broken, reactant molecules must absorb energy from their environment which causes them to enter an unstable state (transition state).

• Once the new bonds are formed, the resulting product is again stable and energy is released to the environment.

• Activation energy: the energy needed to start a chemical reaction- to get the molecules to a place where bonds can be broken- to the transition state

2 types of chemical reactions

• Exergonic: net release of free energy, the free energy of the reactants is greater than the free energy of the products

• Example: cellular respiration• C6H12O6 + 6O2 6CO2 + 6H2O + energy

Figure 6.6a

(a) Exergonic reaction: energy released, spontaneous

Amount ofenergy

released(G 0)

Reactants

ProductsEnergy

Progress of the reaction

Free

ene

rgy

• Exergonic reactions are said to be spontaneous, meaning that is is energetically favorable NOT that it happens quickly.

• Endergonic: absorbs free energy from the surroundings, there is a net increase in energy. The products have more energy than the reactants.

• The products, in a sense store energy.

• Example?

• Photosynthesis• The required energy comes from the sun• 6CO2 + 6H2O + energy C6H12O6 + 6O2

Figure 6.6b

(b) Endergonic reaction: energy required, nonspontaneous

Amount ofenergy

required(G 0)

Reactants

Products

Energy

Progress of the reaction

Free

ene

rgy

Figure 6.6 (a) Exergonic reaction: energy released, spontaneous

(b) Endergonic reaction: energy required,nonspontaneous

Amount ofenergy

released(G 0)

Amount ofenergy

required(G 0)

Reactants

ProductsEnergy

Progress of the reaction

Reactants

Products

Energy

Progress of the reaction

Free

ene

rgy

Free

ene

rgy

Figure 6.12

Transition state

Reactants

Progress of the reaction

Products

G 0

Free

ene

rgy

A

A

A

B

C

D

B

B

C

D

C D

EA

• Draw a similar diagram graphing the progress of an endergonic reaction in which:

•EF + GH EG + FH

•Exergonic• = •Spontaneous• ≠ • fast

Figure 6.12

Transition state

Reactants

Progress of the reaction

Products

G 0

Free

ene

rgy

A

A

A

B

C

D

B

B

C

D

C D

EA

• Adding heat is one way to provide energy to reach the transition state

• Molecules speed up, have more and more forceful collisions with one another

• Some reactions have a small enough activation energy (the amount of energy need to reach the transition state) that they can occur at room temperature

Problems with using heat to speed a biological reaction.

Can you think of any?

• Heat denatures proteins

• All reactions would be accelerated

Enter the enzyme

Enzymes

• Catalyze (speed up) reactions by lowering the activation energy of a reaction

• They cannot change the ΔG for a reaction• They cannot change an endergonic reaction to

an exergonic one.

Figure 6.13

Products

G is unaffectedby enzyme

Reactants

Progress of the reaction

Free

ene

rgy

EA withenzymeis lower

EA withoutenzyme

Course of reactionwithoutenzyme

Course of reactionwith enzyme

Things to know• Enzymes are substrate specific• They bind with their substrate(s) into an

enzyme-substrate complex• Binding occurs at an active site • Remember what we learned about protein

and their ligands, there is some subtle movement in the enzyme after binding that enhances the “fit” of the enzyme to its substrate. Induced fit

Figure 6.14

Enzyme-substratecomplex

Enzyme

Substrate

Active site

Mechanisms of lowering activation energy

1. The active site may provide a template so that multiple substrates can come together in the right orientation

2. The enzyme might stretch on the substrate weakening bonds

3. The active site might provide a microenvironment that is more favorable

4. The enzyme might be directly involved in the chemical reaction, but not consumed.

Figure 6.15-4

Substrates

Enzyme

Substrates areconverted toproducts.

Products arereleased.

Products

Enzyme-substratecomplex

Substrates areheld in active site byweak interactions.

Substrates enteractive site.

Activesite is

availablefor new

substrates.

5

43

21

The rate of a chemical reaction

• Depends on:– Concentration of substrate– Amount of enzyme present– Once saturation occurs, the speed of the reaction

itself limits the rate unless…you can add more enzyme

– Local conditions

Local conditions

• Enzymes have optimum conditions; the conditions under which a particular enzyme works best– Temperature– pH– Cofactors- nonprotein helpers bound to the

enzyme.

Cofactors

• Nonprotein “helpers”• May be bound

– Tightly/ permanently– Loosely/ reversibly

• If the cofactor is organic, called a coenzyme• Example:

– vitamins

Enzyme inhibitors

• Competitive inhibitors– Reduce the productivity of enzymes by blocking

substrates from entering active sites– “mimic” the normal substrate molecule

• Noncompetitive inhibitors– Impede enzymatic reactions by binding to another

part of the enzyme– Changes the shape of the enzyme so that the

active site is less effective

Figure 6.17

(b) Competitive inhibition (c) Noncompetitive inhibition

(a) Normal binding

Competitiveinhibitor

Noncompetitiveinhibitor

Substrate

Enzyme

Active site

Regulation of enzyme activity

• Allosteric regulation= the binding of a regulatory molecule to an enzyme at one site that affects the function of the enzyme at a different site– Inhibition OR– Stimulation

• Cooperativity= a type of allosteric activation in which the enzyme response is amplified by the substrate itself

• Feedback inhibition= the end product of a metabolic pathway acts as a inhibitor of an enzyme within that path.

Figure 6.19 Active site available

Intermediate A

End product(isoleucine)

Intermediate B

Intermediate C

Intermediate D

Enzyme 2

Enzyme 3

Enzyme 4

Enzyme 5

Feedbackinhibition

Isoleucinebinds toallostericsite.

Isoleucineused up bycell

Enzyme 1(threoninedeaminase)

Threoninein active site

Learning objectives

• SWBAT: Create a model that represents the change in free energy of a reaction and the activation energy to carry out that reaction

• SWBAT: Describe how enzymes influence both the change in free energy and the activation energy of a reaction.

• Enzyme video• https://paul-andersen.squarespace.com/048-

enyzmes