Catalysis. v 0 no catalyst v c -- catalyst present. v c. dt with no catalyst) (v c = -d[a]/dt dt with a catalyst)

Transcription

1 Catalysis Catalysis provides an additional mechanism by which reactants can be converted to products. The alternative mechanism has a lower activation energy than the reaction in the absence of a catalyst. A v 0 B v 0 no catalyst v c -- catalyst present v c (v 0 = -d[a]/dt dt with no catalyst) (v c = -d[a]/dt dt with a catalyst)

2 Not affected by catalyst DE Not E a,f Potential Energy E a,f E a,f E Reactants Energy barrier without catalyst E a,r E a,r E a,f and E a,r are by catalyst are lowered Products Energy barrier with catalyst Reaction coordinate

3 Generally a catalyst is defined as a substance which increases the rate of a reaction without itself being changed at the end of the reaction. This is strictly speaking not a good definition because some things catalyze themselves, but we will use this definition for now. Catalyst supplies a reaction path which has a lower activation energy than the reaction in the absence of a catalyst. Catalysis by Enzymes Enzymes may be loosely defined as catalysts for biological systems. They increase the rate of reactions involving biologically important systems.

4 Enzymes are remarkable as catalysts because they are usually amazingly specific (work only for a particular kind of reaction.) They are also generally very efficient, achieving substantial They are also generally, achieving substantial Rate increases at concentrations as low as 10-8 M! Typical enzyme molecular weights are gm/mole (protein molecules)

5 Summary of Enzyme Characteristics 1) Proteins of large to moderate weight ) Extremely efficient (work at 10-8 M) 3) Very specific (work only on special types of reactions). General Behavior of Enzyme Catalyzed Reactions S (substrate) æ E Æ Products If the initial rate of the reaction is plotted versus the initial concentration of substrate S for a constant enzyme concentration, the following behavior is found:

6 V i Initial Rate [S] concentration when V i = V S / 2 Substrate Concentration

7 Maximum initial rate V i Initial Rate (Half maximum initial rate) [S] concentration when V i = V S / 2 Substrate Concentration

8 V s is found to be directly proportional to the total enzyme concentration (E( o ): V s ~ (E( o ) (S) concentration required to reach half maximum initial velocity (V i = V S /2) found to be independent of (E( o ). (S) 1/2 = K M (S) 1/2 Explanation: Michaelis-Menten Menten Mechanism E is free enzyme and ES is an enzyme-substrate complex It may generally be assumed that (S) >> (E) since E are so efficient they catalyze reaction at very small concentration.

9 d (ES) dt = k 1 (E) (S) - k -1 (ES) - k 2 (ES) Step 1 Step 2 Step 3 First Order 0 = d(es) Process dt Steady State assumption: First Order Process (ES) = k 1 (E 0 )(S) k -1 + k 2 + k 1 (S) Second Order Process = k 1 E 0 /[k 1 +(k -1 +k 2 )/(S)] Mechanism k 1 E + S Æ ES Step 1 k -1 ES Æ E + S Step 2 ES Æ P + E Step 3 All are elementary kinetic steps. Divide top and bottom by k 1 to get Æ k 2

10 Bonus * Bonus * Bonus * Bonus * Bonus * Bonus

11 k 2 2 (E 0 ) = k (E ) K m (S) 1 V S /2 2 (S) 1/2 is the substrate concentration when the initial rate reaches half its maximum value. Case III : K m (S) >> 1 dp dt = k 2 (E 0 ) 1 + K m (S) Depends linearly on [S] in region of low substrate concentration.

12 dp dt = V = V max 1 + K m (S) Invert this equation to get--- Mechanism k 1 E + S Æ ES Step 1 k -1 ES Æ E + S Step 2 k 2 ES Æ P + E Step 3 {Lineweaver-Burke Plot} K m is rate at which ES decomposes by two mechanisms (k -1 or k 2 ) divided by rate constant for formation of ES. Large K m fi weak binding of E to S Small K m fi strong binding of E to S K m = k -1 + k 2 k 1

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14 Application of chemical kinetics to ecological and toxicological problems I. Application of enzyme kinetics: l Degradation of organophosphate pesticides Enzymes can be used to catalyze degradation of pesticides While extremely beneficial for protection of crops, pesticides can have serious environmental impact Possible deleterious consequences include seepage of these otherwise helpful chemicals into soil and ground water Case study: organophosphate pesticides l abundant l highly toxic l neutralized via reaction

15 The same enzyme catalysts which can neutralize these pesticides can also be used to detoxify chemical nerve agents. l nerve agents are structurally similar to organophosphate pesticides Nerve gas used General in Japanese formula for subway attack. pesticides l both contain organophosphate esters Degradation product produced in body from parathion paraoxon

16 Recent studies have shown that enzymes, which effectively degrade organophosphates, can be incorporated into polymers -- specifically, foams -- in order to aid in their practical application. One enzyme under current investigation is organophosphorus hydrolase (OPH) a.k.a. phosphotriesterase. Attack by water [derived from Escherichia coli] The degradation reaction of organophosphates works via hydrolysis. (yellow in solution)