1

ENZYMES

Today’s Topics: •  Finish Thermodynamics •  Activation energy •  Enzyme shape

determines function •  Regulation

–  Competitive Inhibitors –  Allosteric Inhibitors

Substrate

Active site

28 Sept 2011 2

decrease in Bond Energy Reduced

Oxidized

increase in Entropy Complex

Simple

The sum of these is the Free Energy (!G) available to do work

Two factors contribute to whether a chemical reaction will occur:

3

!G = !H - T!S

If !G is negative then reaction is energetically favorable or “spontaneous”

4

5 6

2

7 8

Tie a favorable reaction with an otherwise unfavorable reaction

Free

ene

rgy

Progress of the reaction

!G < O

EA

Figure 8.14

A B

C D

Reactants

A

C D

B

Transition state

A B

C D

Products

The energy profile for an exergonic reaction For the reaction to occur:

– reactants must find each other – meet in proper orientation – combine with sufficient force

O || C--OH / R

:O--R | H

O || C--OH

/

R

:O--

R

|

H

O

||

C-

-OH

/

R :O

--R

|

H

O

||

C-

-OH

/

R

:O--

R |

H

Productive orientation Many non-productive orientations

ENZYMES are biological catalysts

•  Usually PROTEINS

Brings substrates together in close proximity

How do Enzymes do it? 1. Enzymes have BINDING AFFINITY for their reactants = Substrates

“Stable” for a few nanoseconds Now close together

3

Figure 8.16

Substate

Active site

Enzyme

(a)

2. Enzymes orient the substrates

The active site Is the region on the enzyme where the substrate binds

OH

HO +

HO

The active site has a very specific 3-D Shape

With a Specific Arrangement of Functional Groups

-

HO

OH

HO

OH

+

HO

OH

SPECIFICITY is the Key to Enzyme Action

Enzymes Bind ONLY specific things

Bind them ONLY in a specific 3-D orientation

2. Enzymes ORIENT Substrates

•  Held in productive orientation O

|| C--OH / R

:O--R | H

Figure 8.16 (b)

Enzyme- substrate complex

3. Enzymes cause Bond Strain

•  Physical

•  Chemical

4. Enzymes contribute to reactions but are not consumed in them

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Rate

Substrate Concentration

An enzyme catalyzed reaction Can become “saturated”

temperature

pH

Things that affect protein structure often affect enzyme activity

Rat

e of

reac

tion

Rat

e of

reac

tion

0 20 40 60 80 100

typical human enzyme

thermophilic bacteria

pepsin trypsin

1 0 2 3 4 5 6 7 8 9 10

Principal Ways of Regulating Enzymes

•  Competitive Inhibition

•  Allosteric Inhibition

•  Covalent Modification (phosphorylation)

-

HO

OH

HO

OH

+

HO

OH

HO

OH

I

S1 S2 Competitive Inhibitors:

•  bind to the active site and block true substrates’ access

Allosteric Inhibitors distort the enzyme so the substrates no longer fit

“other” “site”

(Can also have Positive Regulators that help the

enzyme work Better)

Phosphorylation