An inhibitor acting on multiple enzymes

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Hikmet Emre Kaya

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Oct 14, 2024, 9:30:32 AM10/14/24
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Hello everyone,

If I have an inhibitor that acts on two consecutive enzymes, and the IC50 values for both enzymes are given, can I write the reactions for each enzyme independently, or do I need to merge the two enzymatic reactions and write them in one reaction? The reactions would be in the form:

A --E1-->B; I
B--E2-->C; I
the IC50 is lower for E2 than for E1

It is a bit confusing because it's not clear to me whether the inhibitor first needs to bind E2 completely before it can act on E1, or does it act on both enzymes simultaneously?

Could someone please advise?
Thanks,
Emre

Pedro Mendes

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Oct 14, 2024, 9:40:11 AM10/14/24
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Hi Emre,

you should definitely add the two reactions independently and have each
one of them affected by the inhibitor (with the appropriate IC50).

The inhibitor will bind both enzymes simultaneously, but more to the one
with the lower IC50. Having the two reactions independent with the
appropriate IC50's will ensure that the same happens in the simulation.

Best,
Pedro
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Pedro Mendes, PhD
Professor and Director
Richard D. Berlin Center for Cell Analysis and Modeling
University of Connecticut School of Medicine
group website: http://www.comp-sys-bio.org
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Hikmet Emre Kaya

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Oct 15, 2024, 6:18:32 AM10/15/24
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Dear Prof. Mendes,

I appreciate the clarification! Many thanks.

Emre

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