Enzyme Catalysis Flashcards

1
Q

Acid Base Catalysis

A
  • electron transfer in reactions creates a high energy intermediate state caused by charge separation
  • this is unfavorable and raises energy of activation
  • bases and acts donate or release proteins to create lower energy states by neutralising charges
  • this reduces the energy of activation
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2
Q

general acid/base catalysis

A
  • rate of reaction dependent on the concentration of all acids/bases present in the reaction, not only the proton concentration
  • general bases: Asp, Arg, His
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3
Q

specific acid/base catalysis

A
  • rate of reaction dependent on only proton/hydroxide io concentration
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4
Q

concerted general acid/base catalysis

A
  • both processes occur simultaneously

- bond breakage at the same time as bond formation

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5
Q

Keto-Enol Tautomerisation

A
  • uncatalysed reaction has charge separation with a high energy carbanion TS
  • this is disfavored and reduces spontaneity
  • acids can protonate negative oxygen or bases can deprotonate TS: reduces energy
  • draw mechanisms*
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6
Q

Enzyme Catalyzed Concerted Keto-Enol Tautomerisation

A
  • concerted mechanism: acid protonates carbonyl group as base deprotonates carbon
  • uses amino acid side chains as acids or bases
  • enzymes are more effective due to their concerted mechanism
  • side chains form conjugates and are reset by water
  • enzyme shows activity dependent on the pH of solution, as the side chains can protonate/deprotonate to either become active or inactive
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7
Q

Regulation of Residue pKa

A
  • eg. glutamine has a normal pKa of 3/4
  • if near a hydrophobic region: uncharged favored, pka is raised
  • if near a positive charge: negative charged form is stabilized, lowering pka
  • if near a negative charge: negative charged form is destabilized, pka is raised
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8
Q

Covalent Catalysis

A

rate acceleration through transient formation of catalytic substrate covalent bond

  • 3 stages
    1. nucleophilic reaction between catalyst and substrate
    2. withdrawal of electrons from reaction center by electrophilic catalyst
    3. elimination of catalyst
  • nucleophile must be deprotonated
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9
Q

Activation of Carbonyl Groups to form Schiff Base

A

Schiff Base:

  • C double bonded to NR3 is more reactive because the system is more polarisable
  • protonated form is even more reactive due to resonance and increase polarizability
  • pi cloud shifted over the N to make C extremely electrophilic to aid catalysis
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10
Q

Roles of Covalent Catalysis

A
  1. group transfer reactions

2. increase substrate reactivity: activate it so that product can be formed

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11
Q

Good Covalent Catalyst

A
  • highly nucleophilic
  • good leaving group (highly polarizable)
  • Asp, Lys, Cys, His, Ser
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12
Q

Acetoacetate Decarboxylase

A

uncatalysed: forms enolate ion
charged: stabilised by Lys residue to reduce charge accumulation in TS to lower free energy
- enamine formed, which is neutral so the structure is more stable
* see mechanism*

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13
Q

Electrostatic Catalysis

A

the presence of charges/oriented dipoles within the active site can stabilise the TS via solvation

  • closer charges maximises electrostatic catalysts
  • micro environment of enzyme can be fine tuned to improve charge stabilisation
    eg. non polar residues enhance the energy of interaction
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14
Q

Metal Ion Catalysis

A
  1. metalloenzymes: tightly bound
  2. metal activated enzymes: loosely bound
  • neutralise negative charges, but are extremely effective due to their large charges and high concentrations
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15
Q

Roles of Metal Ions

A
  • electrostatic stabilisation and charge isolation: highly effective because of high charge that is pH independent
  • redox reactions
  • binding and orientation of substrates: act as lewis acids to form dative covalent bonds
  • promote nucleophilic catalysis: activate bound H20
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16
Q

FeS clusters

A
  • redox active cofactors allow electron transfer
  • Fe2+ found is FeS clusters ligated by residues
  • involved in electron transfer
  • found in Complex I: ubiquinone oxidoreductase
  • electron transfer from UQ to UQH2
  • iron cluster chain allows electron hopping
17
Q

Oxidising Water in Photosynthesis

A
  • two molecules of water oxidised to oxygen and four protons/electrons
  • OEC (oxygen evolving clusters): contains manganese ions that exist in multiple oxidation states
  • they are used to soak up and store electrons that are then used to fix carbon dioxide
18
Q

Activating Water

A
  • hydroxide ions are excellent nucleophiles but exist at low concentrations
  • metal ions promote nucleophilic catalysis by ionising water
  • ion’s charge makes its bound water more acidic than free water
  • pka of water is lowered to form metal ion bound OH: a potent nucleophile
19
Q

Carbonic Anhydrase

A

Carbon dioxide + water to give a proton and HCO3-

  • has Zn2+ ion tetrahedrally coordinated by three His side sides and the oxygen of a water molecule
  • OH stabilised by charge interaction and accumulates
20
Q

Orientation and Proximity Effects

A
  • rate enhancement obtained by taking 2 reactants out of solution and placing them next to each other in the active site to raise local reactant concentration
  • correct orientation of orbitals: stereoelectronic assistance
  • unfavorable entropy offset by favorable binding energy because of complementation
21
Q

Preferential TS binding

A
  • enzyme complementary to TS more than substrate
  • stabilization of TS leads to lowering of free energy of activation
    ‘induced fit’ model
22
Q

Coulumbic Energy of Interaction

A
  • dependent on permitivity of medium
  • proportional to inverse of distance between charges
  • maximum in a vacuum