1

1

Energy and Enzymes Today�s Topics •  Coupled Reactions

–  ATP

•  How do Enzymes Work? –  Activation energy –  Active site

•  Enzyme Regulation –  Competitive & Allosteric

•  Enzymes are Linked in Metabolic Pathways

•  Oxidation and Reduction September 27, 2021 2

Tie a favorable rxn with An otherwise unfavorable rxn COUPLED Reactions

ATP

Adenine

3 phosphate groups Ribose

4

ΔG = +5.5 kcal/mole

1.

ΔG = -7.3 kcal/mole

2. ATP+ H2O ADP + Pi

Favorable or unfavorable ?

Favorable or unfavorable ?

Coupled Reactions

Each step is favorable

Figure 3.13 Enzymes Lower the Energy Barrier Ea

Products

Time course of reaction

Free

ene

rgy

(G)

ΔG

Ea

Reactants

Catalyzed reaction

Uncatalyzed reaction

2

Substrates enter active site.

Substrates are held in active site by weak interactions.

Substrates Enzyme-substrate complex

Active site is available for new substrates.

Enzyme

Products are released.

Products

The active site lowers EA.

Substrates are converted to products.

1 2

3

4 5

6 OH

HO +

HO

Polar Nonpolar

Charged The active site has a specific 3-D Shape

With a specific arrangement of functional groups

Figure 8.16 (b)

Enzyme- substrate complex

Enzymes cause Bond Strain

•  Physical

•  Chemical

Figure 8.13

A B

C D Transition state

A

C

B

D

A

C

B ∆G < 0

D

Products

Free

ene

rgy EA

Reactants

Progress of the reaction

Asp 52

Glu35

Chemical bond strain: Two charged amino acids pull on the bonds

Lysozyme example

Physical bond strain: Binding to the enzyme flattens the zig-zag shape, which stretches the bonds

Figure 3.14 Enzyme Action Active site

Sucrose

Fructose

Glucose

Water

Enzyme (sucrase)

O

OO

O

OO

O

O

OH

HO

H2O

O O4. Enzymes contribute to reactions but are not consumed in them

3

Principal Ways of Regulating

Enzymes

•  Competitive Inhibition

•  Non-competitive (Allosteric) Inhibition

•  Covalent Modification (phosphorylation)

-

HO

OH

HO

OH

+

HO

OH

HO

OH

I

S1 S2

S & I bind to same site

Competitive Inhibitors: •  bind to active site �unproductively� and block true substrates� access

I

S1 S2

Depends on relative concentration

Allosteric Inhibitors distort the enzyme so the substrates no longer fit

�other����site�

(Can also have Positive Regulators that help the enzyme work

better)

Covalent regulators: Phosphorylation

Enzymes are specific, so each chemical reaction in a cell usually has its own enzyme

Enzyme 1

Reaction 1 Starting molecule

Enzyme 2 B

Reaction 2 C

Enzyme 3

Reaction 3 D

Product

A

4

Metabolism ofCofactors and Vitamins

Nucleotide Metabolism

CarbohydrateMetabolism

LipidMetabolism

Amino AcidMetabolism

ATPProduction

Metabolism ofOther Substances

Enzymes control metabolic pathways

Each step catalyzed by a different enzyme

Feedback Loops Initial substrate (threonine)

Active site available

Threonine in active site

Enzyme 1 (threonine deaminase) Isoleucine

used up by cell

Feedback inhibition

Active site no longer available; pathway is halted

Intermediate A

Enzyme 2

Intermediate B

Enzyme 3

Isoleucine binds to allosteric site.

Intermediate C

Enzyme 4

Intermediate D

Enzyme 5

End product (isoleucine)

21

Atoms bonded in High Potential Energy Configuration

Atoms bonded in Low Potential Energy Configuration

Chemical Products have a lower Potential Energy than Reactants

Energy is Released

If one thing gets oxidized, another becomes reduced

23

CH4

H

H

H

H C O O O O O C

H H

Methane (reducing agent)

Oxygen (oxidizing agent)

Carbon dioxide Water

+ 2O2 CO2 + Energy + 2 H2O

becomes oxidized

becomes reduced

Reactants Products

Sometimes an electron Is only partially lost or gained

Change the degree of electron sharing in covalent bonds

Oxidation, Reduction, and Energy