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Mechanism of Substrate Binding
Emma_5484
#1 Posted : Sunday, August 09, 2020 1:35:18 PM
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Hi there,

While doing the AAMC FLE4 I came across some terminology in a question about enzymes and substrate binding that I wasn't familiar with. Would you be able to explain the difference between random order, ordered, and ping pong substrate binding?

Thanks,
Emma
INSTR_Katerina_102
#2 Posted : Monday, August 10, 2020 4:51:54 AM
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Hi Emma,

For all of these, let's assume an overall reaction of an enzyme reacting with 2 substrates in an overall reaction:

(A) E + S1 + S2 --> E + P1 + P2

There are multiple mechanisms by which this can be achieved:

1.Sequential reactions:
both substrates must be present inside the active site of the enzyme to transform S into P.

In other words:

(B) E + S1 + S2 --> S1-E-S2 (a ternary complex incorporating S1, S2 and E) --> E + P1 + P2

Mechanism (B) can happen in two different ways:

1 a) in ordered sequential reactions
, the order in which S1 and S2 attach themselves to E to form the ternary complex matters, that is you have to have something like:

(C) E + S1 --> E-S1 +S2 --> E-S1-S2 --> E + P1 + P2 where S1 must bind to E before S2

1 b) in random order sequential reactions, the order in which S1 and S2 attach themselves to E does not matter, so you can have mechanism (C) or (D) occuring as follows (and both occur to some extent)

(C) E + S1 --> E-S1 +S2 --> E-S1-S2 --> E + P1 + P2
(D) E + S2 --> E-S2 +S1 --> E-S2-S1 --> E + P2 + P1

2. Ping pong substrate binding does not involve the formation of an E-S1-S2 complex (ternary complex) like in these sequential mechanisms.

Instead, the two substrates enter the active site at different intervals as follows:

(E) E + S1 + S2 --> E-S1 + S2 --> E* + P1 + S2 --> E*-S2 + P1 --> E + P1 + P2

Where E* is an enzyme temporarily modified by reaction with S1, often you are passing a group from S1 to S2 in this process using the enzyme as an intermediary.

This is a bit complicated and I would be surprised if the MCAT gave you this without the context of a passage.

Please let me know if this is unclear,

Katt
Emma_5484
#3 Posted : Monday, August 10, 2020 12:19:18 PM
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Hi Katt,

Thank you for explaining, that makes sense. It was a question asked in a passage on one of the AAMC FLE's without any context given in the passage so I will definitely learn it in case it comes up again.

Emma
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