Phar 430 - Enzyme Function/inhibition

Front 1

What is the definition of a Catalyst?

Back 1

A substance that accelerates the rate or ease of a chemical reaction without itself being changed or consumed in the end

Front 2

What is the definition of Gibb's Free Energy?

Back 2

The energy portion of a thermodynamic system available to do work

Front 3

What does an enzyme do to a reaction?

Back 3

The enzyme's major role isn't to affect the equilibrium of a reaction, but rather to affect the rate at which the equilibrium is reached, by lowering the energy of activation.

Front 4

What are the mechanistic considerations for Enzymes? (4)

Back 4

1) Binds to reaction substrates and products to varying degrees, but binds to TS quite well

2) Increases the effective concentration of reactants by bringing them in proximity to one another

3) Holds reactants in an optimal orientation for catalysis

4) Covalent chemistry effects occur when a covalent bond is made by the enzyme (or bound cofactor) to its substrate being transformed

Front 5

What is the characteristic of a competitive inhibitor of the enzyme?

Back 5

If the enzyme binds preferentially to the Transition State then it can be expected that a TS analogue can be a potent competitive inhibitor of the enzyme

Front 6

"Tethered reactions have a faster rate than non-tethered reactions" True or False?

Back 6

TRUE

Front 7

What are the components of the Chymotrypsin active site? (4)

Back 7

1) Asp102

2) His57

3) Ser195

4) Oxyanion Hole

Front 8

What is Vmax?

Back 8

The theoretical maximal rate at which the total enzyme concentration is making product

Front 9

What is Km?

Back 9

The substrate concentration at which the rate of the reaction is half maximal

Front 10

"Km is considered a constant for an enzyme's affinity for its substrate" True or False?

Back 10

TRUE

Front 11

What does the rate constant for the enzyme reaction become when k2>>k-1?

Back 11

kcat/km = k1

Front 12

What is the definition of an Enzyme Inhibitor?

Back 12

A substance that reduces an enzyme's activity by combining with it in such a way that influences the binding of substrate and/or its catalysis

Front 13

What are the different ways an Inhibitor can bind?

Back 13

Inhibitors can bind irreversibly or reversibly to the active site or to the allosteric site.

Front 14

What is Irreversible Inhibition?

Back 14

The instance when an inhibitor binds covalently or very tightly to an enzyme in a way that prevents it from functioning

Front 15

What is "Inhibition Efficiency"?

Back 15

The apparent second order rate constant for enzyme inactivation

Front 16

What are examples of Irreversible Inhibitors? (7)

Back 16

1) Sarin

2) Cyclosarin

3) Tabun

4) Soman

5) Dyflos

6) VX

7) Acethycholine

Front 17

What does Oxidative Desulfrization do and why does it result in toxcities found in animals?

Back 17

Converts Malathion into its toxic metabolite Malaoxon.

This can result in toxicities found in animals

Front 18

What are "Active Site Directed Irreversible Inhibitors"?

Back 18

Chemical entities inherently reactive & indiscriminate, thus offering little therapeutic value

Front 19

What is an example of Active Site Directed Irreversible Inhibitors?

Back 19

TPCK

Front 20

What are "Mechanism based irreversible inhibitors"?

Back 20

These "suicide substrates" are highly & selectively reactive toward an enzyme's catalytic cycle.

They are differentiated from active site directed inhibitors in that they have an extra level of built in selectivity.

Front 21

What is an example of Mechanism based irreversible inhibitors?

Back 21

Penicillin & Aspirin Alkylate

Front 22

What are the suicide substrate requirements? (5)

Back 22

1) Inactivation should be time dependent (reaction is irreversible)

2) Kinetics should be first order with respect to X

3) The enzyme should show saturation kinetics

4) The substrate should be able to block the enzyme 5) Stoichiometry of the reaction should be 1:1

Front 23

What is Reversible Inhibition?

Back 23

The instance when an inhibitor exists in equilibrium with the enzyme it affects.

Front 24

What is a Competitive Inhibitor?

Back 24

When an inhibitor competes with substrate for free enzyme to form enzyme:inhibitor complex

Front 25

What is a Uncompetitive Inhibitor?

Back 25

When an inhibitor binds only to the enzyme:substrate complex to form an enzyme:substrate:inhibitor complex

Front 26

What is a Mixed Inhibitor?

Back 26

When an inhibitor binds to the free enzyme OR the enzyme:substrate complex

Front 27

What is effect of competitive inhibition on Vmax apparent and Km apparent?

Back 27

Vmax apparent = Vmax. Km apparent = αKm.

Front 28

What is effect of uncompetitive inhibition on Vmax apparent and Km apparent?

Back 28

Vmax apparent = Vmax/α'. Km apparent =Km/α'.

Front 29

What is effect of mixed inhibition on Vmax apparent and Km apparent?

Back 29

Vmax apparent = Vmax/α'. Km apparent =αKm/α'.

Front 30

What is effect of non-competitive inhibition on Vmax apparent and Km apparent?

Back 30

Vmax apparent = Vmax/α'. Km apparent =αKm/α'; α=α'

Front 31

What are the methods that Ki can be determined? (2)

Back 31

1) Lineweaver-Burke Plot 2) Eadie-Hofstee Plot

Front 32

What is IC50?

Back 32

The concentration of inhibitor required to inhibit an enzyme by 50%