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Missing reversibility on Estrone <=> Estradiol reaction #961

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oxinabox opened this issue Jan 2, 2025 · 3 comments
Open

Missing reversibility on Estrone <=> Estradiol reaction #961

oxinabox opened this issue Jan 2, 2025 · 3 comments
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@oxinabox
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oxinabox commented Jan 2, 2025

It is known that there is a bidirection reaction:
to/from Estrone and Estradiol
However, I can only locate a single direction reaction from
Estrone to Estradiol.

The reaction I believe should be changed is:
MAR02036 Estradiol-17beta:NADP+ 17-oxidoreductase (and it's partner in other compartments)

estrone [c] + H+ [c] + NADPH [c] --> estradiol-17beta [c] + NADP+ [c]

This currently has a lower-bound of 0, and I believe it should have the lowerbound of -1000, like other bidirection reactions.

This reaction has the CVTerm for https://identifiers.org/kegg.reaction/R02353
which is a bidirectional reaction.

It could be that there should instead be the reverse reaction in the Endoplasmic Reticulum (rather than being bidirectional in both.

estradiol-17beta [r] + NADP+ [r] --> estrone [r] + H+ [r] + NADPH [r]

I am not sure. But that also is not present.


I am generating some charts from the GEM, via merging across compartments.
And I noted that it looked wrong

flowchart TD
        testosterone("Testosterone      (<a href='https://en.wikipedia.org/wiki/Testosterone'>⛓</a>)")
        estradiol-17beta("Estradiol     (<a href='https://en.wikipedia.org/wiki/Estradiol'>⛓</a>)")
        16alpha-hydroxyestrone("16α-Hydroxyestrone      (<a href='https://en.wikipedia.org/wiki/16%CE%B1-Hydroxyestrone'>⛓</a>)")
        estrone("Estrone        (<a href='https://en.wikipedia.org/wiki/Estrone'>⛓</a>)")
        5-alpha-dihydrotestosterone("Dihydrotestosterone        (<a href='https://en.wikipedia.org/wiki/Dihydrotestosterone'>⛓</a>)")
        estriol("Estriol        (<a href='https://en.wikipedia.org/wiki/Estriol'>⛓</a>)")

        testosterone --> estradiol-17beta
        estrone --> 16alpha-hydroxyestrone
        estradiol-17beta --> estriol
        testosterone --> 5-alpha-dihydrotestosterone
        16alpha-hydroxyestrone --> estriol
        estrone --> estradiol-17beta
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@oxinabox oxinabox added the bug label Jan 2, 2025
@JHL-452b
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JHL-452b commented Jan 3, 2025

There is a reaction represented estrone to estradiol-17beta in the endoplasmic reticulum, you can refer to MAR02041.

In the current model, MAR02041 and MAR02036 have the same GPR and direction ([0, 1000]).

MAR02041: estrone [r] + H+ [r] + NADPH [r] --> estradiol-17beta [r] + NADP+ [r]
MAR02036: estrone [c] + H+ [c] + NADPH [c] --> estradiol-17beta [c] + NADP+ [c]

The evidences[1, 2] I can find now is that these two reactions should be reversible. But there is no information that supposed MAR02041 should be backwards in the ER. Do you have any other evidence that this reaction should be in the opposite direction?

@oxinabox
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oxinabox commented Jan 3, 2025

My expectation was that they would both be reversible yes.

Re: the other possibility of being in opposite directions in the compartments someone suggested to me based on this Wikipedia page (https://en.wikipedia.org/wiki/17β-Hydroxysteroid_dehydrogenase) which
has reduction in the Cytosol and Oxidation in the Endoplasmic Reticulum.
But the person who suggested it wasn't sure, and I haven't dug further.

@JHL-452b
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JHL-452b commented Jan 3, 2025

Anyway, I agree to change the MAR02041 and MAR02036 to be bidirectional.

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