10

Question 1

Where does enzyme substrate binding occur

Answer 1

Active site

Question 2

How does the active site bind to substrate

Answer 2

Active sitre bind to substrates via several weak interactions

Question 3

What determines the specify of the reaction

Answer 3

The active site

Question 4

What do many weak interactions ensure

Answer 4

Specificity and reversablitly

Question 5

Contridion for weak bonds to form

Answer 5

Weake bonds can only form if real ent atoms are precisely postitioned

Question 6

It is ____ to break weak bonds

Answer 6

It is easier to break weak bonds

Question 7

Molecular ______ between ___ and ____ is critical

Answer 7

Molecular complementarity between exhume and substrate is critical

Question 8

Enzymes show

Answer 8

Geometric and stereospecififity

Question 9

Two models for enzyme-substrate binding

Answer 9

-Locke and key
- induced fit

Question 10

Provided the ____ of the ____ _____ is _____, the enzyme can ______ between ______ groups on the _______

Answer 10

Provided the shape of the active site is asymmetric, the enzyme can distinguish between identical groups on the substrate

Question 11

Ezymes are _____ not. _____

Answer 11

Dynamic not static

Question 12

Types on enzyme substrate bonds

Answer 12

• ionic bonds
• hydrogen bonds
• van der walls interations
• covalent bonds

Question 13

Ionic bonds (salt bridges)

Answer 13

• uses charges side chains (Asp,Blu,Arg,Lys)

Question 14

Hydrogen bonds

Answer 14

Side chain or backbone O and N atoms can often act as hydrogen bond acceptors and donors

(Only happen when two groups are in correct orientation)
(- connections between substrates and active site redidues within enzymes)

• need side chains for diversity

Question 15

Van der walls interactions

Answer 15

Between any protein and substrate atoms in close proximity: weakest of all interations

Not much specificity

Question 16

Weakest interactions

Answer 16

Van der walls

Question 17

Example of realises weak interactions and covalent interations

Answer 17

• ionic bonds
• hydrogen bonds
• van der walls interactions
• covalent

Question 18

Covalent bonds

Answer 18

• between active sites and amino acid side chains
• relatively rare - much stronger then other bonds

Question 19

What happens when hexokinase binds a substate

Answer 19

Conformational change

Question 20

3 wats active energy is lowered

Answer 20

1. Groundstate destabilisation (trough up)
2. Transition state stabilisation (trough down)
3. Alternate reaction pathway with a different “(or lower energy) transition state

1 and 2 can be achieved the same way: by having an active sire that has shape/charge complementarity to the TS, not the substate

Question 21

Catalytic mechanisms (common to all enzymes vs specific to reaction pathway)

Answer 21

1. Preferential binding of the transition state
2. Proximity and orientation effects
3. Acid-base catalyst
4. Metal ion catalysis
5. Covalent catalysis

Question 22

How prefectural binding of the transistor state happens

Answer 22

An enzyme bind the transition state more tightly then it binds the substate
Transition states are transient and cannot be isolated (they are very high energy) —> need to design and synthesise an analogue

An analogue is something the looks like the transition state but cannot be turned into a substrate

Question 23

Enzymes catalyse thrermodyntmaclly favourable reactions

Answer 23

by lowering the activation enenery

Question 24

Transition state shit - maybe go over this

Answer 24

Question 25

transition state analogues as drugs - how?

Answer 25

Lipitor = powerful cholesterol-lowing drug - it inhibits HMG-CoA reductase (within the biosynthetic pathway for chlolesterol) - Liptor is a transition state analogue of the HMG-CoA reductase reaction pathway - Lipitor looks more like the transition state so it binds to active site

Question 26

If you want an inhibitor…

Answer 26

Use something that looks like the transition state

Question 27

How transition state analogues are good drugs

Answer 27

- enzymes are often targets for drugs and other beneficial agents - transition state analogues often make ideal enzyme inhibitors

Question 28

What does analapril and aliskiren do?

Answer 28

- lower blood pressure

Question 29

What do statins do?

Answer 29

Lower serum cholesterol

Question 30

What are protease inhibitors?

Answer 30

AIDS drugs (transition state analogue of transition state hiv proteases)

Question 31

What is a Juvenile hormone esterase

Answer 31

A pesticide target (

Question 32

What is Tamiflu ?

Answer 32

An inhibitor of influenza neuraminidase (transition state

Question 33

For two molecules to react they need to be

Answer 33

- close together (proximity) - in the correct orientation

Question 34

The reaction hexokinase catalyses and how it shows probity and orientation hexokinase is enabling through chemical reaction

Answer 34

- taking a phosphate off an atp and put onto glucose - hexokinase has evolved An active site that binds glucose in its complementary way and also bind ATP adjacelntly with its phosphate group postitoned at its perfect place to be transferred onto the hydroxyl of the glucose

Question 35

What does acid-base catalysis involve?

Answer 35

Proton H+ transfer (must have side chains that can exchange protons - end=zyems with these residues in their active sites might have high or low activity depending on the pH of the solution and the environment at the active site

Question 36

Which amino acid is particularly suitable to acid base reactions?

Answer 36

Histidine

Question 37

Why is histidine so suitable for acid base reactions

Answer 37

- pKa (his) ~ 6.5 (close to physiological pH) - depending on the environment of the active site, his can dontate or accept a proton

Question 38

At least a third of known enzymes require ____ _____ for catalytic activity

Answer 38

Metal ions

Question 39

Metal ions provide:

Answer 39

- substrate orientations -> due to their specific coordination geometry - ability to act as a Lewis acid (electron acceptors) to polarise H2O molecules or other functional groups - sites for electron transfer ( redox reactions)

Question 40

Metal ions may be ______ at active enzyme sites

Answer 40

Cofactors

Question 41

Hexokinase uses ___ as a cofactor

Answer 41

Mg2+

Question 42

At the active site of hexokinase - diagram

Answer 42

Question 43

What does Mg2+ do in the active site of hexokinase

Answer 43

Mg2+ ion balances negative charge of the transition state

Question 44

What is covalent catalysis?

Answer 44

- involves the formation of a reactive, short-lived intermediate, which is covalently attached to the enzyme - can have a nucleophillic side chain form a short lived intermediate which is covalent with the substrate - b gets cleaved off - water can then atack that bond and A is also then cleaved

Question 45

The enzyme - substrate interaction relies on

Answer 45

multiple, weak interactions and (often) induced fit

Question 46

Ezymes preferentially bind and ______ the _____ ______

Answer 46

Enzymes preferentially bind and stabilise the transition state

Question 47

There are a variety of _____ _____, for providing alternate reaction routes compacted to the ________ ______

Answer 47

There are a variety of catalytic mechanisms,for providing alternate r reaction routes compared to the uncatalysed reaction