Mechanisms Inhibitors

Question 1

What is a ternary complex

Answer 1

A complex where the enzyme is attached to two substrates
E (s1)(s2)

Question 2

What are bimolecular reactions

Answer 2

A + B turns into C + D

Question 3

What are sequential reactions

Answer 3

The reaction where a terinary complex is formed (e and the two substrates) then two products are released

Question 4

In the cleland representation of a bimolecular reaction in which ways can the substrates bind to the enzyme

Answer 4

Either ordered (a binds first then B) or random (B then A)

Question 5

What are double displacement reactions

Answer 5

Also called ping pong reactions,

They are bi molecular reactions where a substituted enzyme intermediate is formed

Ex. The enzyme produces product c
First and turns into E-x (intermediate) then makes product d

Meaning 1 or more products a first released before all of the reactants bind to the enzyme

Question 6

What are calatylic strategies

Answer 6

Enzymes use one or more of these strategies to catalyze a reaction and facilitate formation of the transition state

Question 7

What are the four calatylic strategies

Answer 7

Covalent catalysis

General acid base catalysis

Metal ion catalysis

Catalysis by approximation and orientation

Question 8

What is covalent catalysis

Answer 8

The active site of the enzyme has a reactive group that becomes covalemtly modified during catalysis

Ex. The oh side chain of serine bonds to the substrate covalently to make the acyl enzyme

Question 9

What is general acid base catalysis

Answer 9

A molecule (not water) plays the role of a proton acceptor (general base) or a proton donor (general acid)

Ex. His 57 acts as a base and accept a proton from ser 195s OH group to make it a better nucleophile

Question 10

What is metal ion catalysis

Answer 10

The metal ions help by:

Generating a nucleophile by increasing the acidity of a nearby molecule like water (ex. Zinc making water deprotonated itself)

Increasing the binding energy through interaction with the substrate

Stabilizing the negative charge on a reaction intermediate (to make reaction go faster)

Question 11

What are the two catalytic strategies in invertase enzyme

What type of bimolecular reaction is it

Answer 11

Covalent catalysis and general acid base catalysis

Double displacement

Question 12

What is catalysis by approximation and orientation

Answer 12

The two substrates first bound to an enzyme then are brought close to each other and out in the correct orientation

Ex. A-ppp is close to ap

This makes one of the p easily switch to the app to make 2 ADP

Question 13

What are inibitors

Answer 13

Small molecules that bind to enzymes and inhibit their activity

Exist in nature as toxins or poisons or are made by chemists

In terms of binding to the enzyme they can be reversible or irreversible

Question 14

What are reversible inhibitors

Answer 14

They bind to and dissociate from the enzyme quickly

There are three types and they differ based on how the inhibitor interacts with the enzyme

Question 15

What are the three types of reversible enzyme inhibitors

Answer 15

Competitive

Uncompetitive

Non competitive

Question 16

What are competitive inhibitors

Answer 16

The inhibitor looks like the substrate and binds to the active site

As the concentration of the inhibitor increases we need higher concentration of the substrate to get a certain velocity

The inhibitor has no effect on Vmax (reaches Vmax after longer time) but it increases Km

Question 17

What is uncompetitive inhibitition

Answer 17

The inhibitor binds to the enzymes substrate complex (the inhibitor is on the enzymes and this is bound there as well)

This causes an ESI (enzyme substrate inhibitor complex) where now product is formed

Both km (k1 goes up since ES complex is made) and Vmax decrease which causes parallel lines on the burk graph

Question 18

What are non competitive inhibitors

Answer 18

Inhibitor binds to a spot on the enzyme other than the active site when there’s no substrate in it, or to the enzyme substrate complex

This means both the ESI complex and the EI complex don’t make any product

Vmax decreases and Km is same (because inhibitor doesn’t affect binding of substrate)

Question 19

What are irreversible inhibitors

Answer 19

They’re either covenlently bound of very tight non covalenty bound to the enzyme

They’re use in experiments to determine the mechanism of the enzyme

Question 20

What are the types of irreversible inhibitors

Answer 20

1. Group specific reagent
2. Affinity label
3. Transition state analog

4 suicide inhibitor

Question 21

What is a Group specific reagent

Answer 21

It modifies the r group of a specific amino acid

It’s only specific for the one r group on the enzyme, not specific for entire enzymes

Question 22

What are affinity labels

Answer 22

Structurally similar to the substrate so they bind to a specific enzyme (not just aa residue)

They covelently modify AA residues of the enzymes active site

Question 23

What are transition state analogs

Answer 23

They inhibit an enzyme by binding to the enzymes active site and mimicking the transition state

Natural tradition states are short live and unstable, but the analog is very stable.

So They bind even more tight to the active site than the actual intermediate

Question 24

What are suicide inhibitors

Answer 24

A chemically modified substrate that binds and is initially processed by the enzyme

The catalysis process of it leads to a chemically reactive intermediate that inactivates the enzyme

This is because the covalent modification of the enzyme (substrate binding to it) causes the enzyme to become inactive and terminates any other reactions