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An Introduction to Metabolism
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Inhibitor

Non-

functional

active

site

Stabilized inactive

form

Inactive form

Oscillation

Activator

Active form

Stabilized active form

Regulatory

site (one

of four)

Allosteric enzyme

with four subunits

Active site

(one of four)

Slide 68

Cooperativity is a form of allosteric regulation that can amplify enzyme activity

Cooperativity is a form of allosteric regulation that can amplify enzyme activity

In cooperativity, binding by a substrate to one active site stabilizes favorable conformational changes at all other subunits

Slide 69

Fig. 8-20b

Fig. 8-20b

(b) Cooperativity: another type of allosteric activation

Stabilized active

form

Substrate

Inactive form

Slide 70

Identification of Allosteric Regulators

Identification of Allosteric Regulators

Allosteric regulators are attractive drug candidates for enzyme regulation

Inhibition of proteolytic enzymes called caspases may help management of inappropriate inflammatory responses

Slide 71

Fig. 8-21

Fig. 8-21

RESULTS

EXPERIMENT

Caspase 1

Active

site

SH

Known active form

Substrate

SH

Active form can

bind substrate

SH

Allosteric

binding site

Known inactive form

Allosteric

inhibitor

Hypothesis: allosteric

inhibitor locks enzyme

in inactive form

S–S

Caspase 1

Active form

Allosterically

inhibited form

Inhibitor

Inactive form

Slide 72

Fig. 8-21a

Fig. 8-21a

SH

Substrate

Hypothesis: allosteric

inhibitor locks enzyme

in inactive form

Active form can

bind substrate

S–S

SH

SH

Active

site

Caspase 1

Known active form

Known inactive form

Allosteric

binding site

Allosteric

inhibitor

EXPERIMENT

Slide 73

Fig. 8-21b

Fig. 8-21b

Caspase 1

RESULTS

Active form

Inhibitor

Allosterically

inhibited form

Inactive form

Slide 74

Feedback Inhibition

Feedback Inhibition

In feedback inhibition, the end product of a metabolic pathway shuts down the pathway

Feedback inhibition prevents a cell from wasting chemical resources by synthesizing more product than is needed

Slide 75

Fig. 8-22

Fig. 8-22

Intermediate C

Feedback

inhibition

Isoleucine

used up by

cell

Enzyme 1

(threonine

deaminase)

End product

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