NTR: acetaldehyde dehydrogenase (NADP+?) activity

[ValWood]

Please provide as much information as you can:

• Suggested term label:

similar to #29540 (comment)
we only have a generic aldehyde dehydrogenase.
https://www.ebi.ac.uk/QuickGO/GTerm?id=GO:0004029 with multiple children

I would like a child of aldehyde dehydrogenase
for modelling ethanol detoxification pathway precisely

• Definition (free text)

Catalysis of the reaction: acetaldehyde + NADP+ + H2O = acetic acid/acetate + NADPH + H+.

• Reference, in format PMID:#######
  (REQUIRED)

• Gene product name and ID to be annotated to this term
  https://www.pombase.org/gene/SPAC9E9.09c
  https://www.pombase.org/gene/SPAC922.07c

• Parent term(s)

• Children terms (if applicable) Should any existing terms that should be moved underneath this new proposed term?

• Synonyms (please specify, EXACT, BROAD, NARROW or RELATED)

• Cross-references

• For enzymes, please provide RHEA and/or EC numbers.

• Can also provide MetaCyc, KEGG, Wikipedia, and other links.

• Any other information

[ValWood]

I can't locate a Rhea for this but there are plenty of references in
https://www.niaaa.nih.gov/publications/alcohol-metabolism#:~:text=Most%20of%20the%20ethanol%20in,tissues%20other%20than%20the%20liver.

[sjm41]

Are you sure you want the NADP version?

The NADP version is RHEA:25298
acetaldehyde + NADP(+) + H2O = acetate + NADPH + 2 H(+)
That would be a child of GO:0033721 aldehyde dehydrogenase (NADP+) activity

The NAD version is https://www.rhea-db.org/rhea/25294
acetaldehyde + NAD(+) + H2O = acetate + NADH + 2 H(+)

RHEA:25294 is currently a narrow xref on the parent term GO:0004029 you mention, so we could remove that and create the new child term.

[ValWood]

currently we have

GO:0004029 | aldehyde dehydrogenase (NAD+) activity | IBA with 68409 , 620252 , MGI:1861722 , 69219 , Q4WCK7 , S000005901 , P08157 , Q43274 , MGI:1353450 , FBgn0012036 , P05091 , P48644 , P00352 , S000000875 , P17445 , 2087 , PTN000192421 , P49189

by IBA which is why I suggested NAD+

(Although I think chatGPT mentioned that the enzyme could use NAD or NADP, I will see if I can find support for this)

[ValWood]

Im looking at
https://dev.pombase.org/gene/SPAC9E9.09c

[sjm41]

Your original request was for a child of the NAD version (GO:0004029) but then the reaction you provided stated NADP:

Catalysis of the reaction: acetaldehyde + NADP+ + H2O = acetic acid/acetate + NADPH + H+.

So, just need to clarify which you need - NAD or NADP!

[ValWood]

S. cerevisiae has 3 paralogs
YER073W ALD5
Mitochondrial aldehyde dehydrogenase; involved in regulation or biosynthesis of electron transport chain components and acetate formation; activated by K+; utilizes NADP+ as the preferred coenzyme; constitutively expressed

YOR374W ALD4
Mitochondrial aldehyde dehydrogenase; required for growth on ethanol and conversion of acetaldehyde to acetate; phosphorylated; activity is K+ dependent; utilizes NADP+ or NAD+ equally as coenzymes; expression is glucose repressed; can substitute for cytosolic NADP-dependent aldehyde dehydrogenase when directed to the cytosol; polymerizes into filaments in meiotic cells; human homolog ALDH2 can complement yeast ald4 mutant

YPL061W ALD6
Cytosolic aldehyde dehydrogenase; activated by Mg2+ and utilizes NADP+ as the preferred coenzyme; required for conversion of acetaldehyde to acetate; constitutively expressed; localizes to the mitochondrial outer surface upon oxidative stress; negative regulator of nonselective autophagy; Stb5p directly regulates the expression of ALD6 mRNA and directly binds to the ALD6 promoter

So I suspect the pombe single copy can probably use NAD/NADP either!
Can we have NAD(P)?
What do we normally do in this situation?

[sjm41]

So we already have this parent term that covers both:
GO:0004030 aldehyde dehydrogenase [NAD(P)+] activity

And then I see that we have a child of that term that also covers both, with specific grandchildren
GO:0019115 benzaldehyde dehydrogenase [NAD(P)+] activity
...GO:0018477 benzaldehyde dehydrogenase (NADP+) activity
...GO:0018479 benzaldehyde dehydrogenase (NAD+) activity

So there's a precedent for doing this:
NTR acetaldehyde dehydrogenase [NAD(P)+] activity
...NTR acetaldehyde dehydrogenase (NADP+) activity RHEA:25298
...NTR acetaldehyde dehydrogenase (NAD+) activity RHEA: 25294

Would be good to get @pgaudet's view when she's back.

[ValWood]

OK, not urgent, thanks

[ValWood]

If we have an editors call can we discuss this?
Required for a GO-CAM

[ValWood]

@pgaudet spotted that some of the activities are not aligned for acetaldehyde /aldehyde in the definitions.

Also many NADH/NADHP aldehydes are not children of the generic term

[pgaudet]

Can you specify the actions you're requesting ?
It seems the NADP+ reaction is in GO

Which children is it missing?

[ValWood]

The problem is that I am annotating the orthologs (2 paralogs) of S. cerevisiae acetaldehyde. S. cerevisiae has 4 copies with various substrate specificity, some NADP+ as the preferred and some NAD/NADP equally. I can't guess the pombe gene specificity, so I wanted to annotate to an agnostic parent NAD(P) term that is agnostic to NAD/NADP .

This seems to be the practice for other terms so I would need
NTR acetaldehyde dehydrogenase [NAD(P)+] activity
(note I need specifically acetaldehyde not just the generic aldehyde to complete

the current IBA annotations are imprecise because they refer explicitly to NAD+ (which is not a given), and because they
are a generic grouping terms referring to aldehyde rather than acetaldehyde
https://www.pombase.org/gene/SPAC922.07c
https://www.pombase.org/gene/SPAC9E9.09c

[pgaudet]

There is something confusing in RHEA:
https://www.rhea-db.org/rhea/25298
is linked to EC 1.2.1.4 aldehyde dehydrogenase (NADP(+))

but shows acetaldehyde as a substrate.

@kaxelsen Can this be clarified?

Thanks, Pascale

[kaxelsen]

RHEA:25298 (acetaldehyde) is a child of RHEA:11888 (aldehyde). As acetaldehyde is not mentioned in the entry for EC 1.2.1.4 at IUBMB, I will remove RHEA:25298 from the EC number.

[pgaudet]

+[Term]
+id: GO:0140087
+name: acetaldehyde dehydrogenase (NAD+) activity
+namespace: molecular_function
+def: "Catalysis of the reaction: acetaldehyde + NAD+ + H2O = acetate + NADH + 2 H+." [PMID:9473035, RHEA:25294]
+xref: RHEA:25294
+is_a: GO:0004029 ! aldehyde dehydrogenase (NAD+) activity
+property_value: term_tracker_item "#29544" xsd:anyURI
+created_by: pg
+creation_date: 2025-01-28T07:26:40Z
+
+[Term]
+id: GO:0140088
+name: acetaldehyde dehydrogenase (NADP+) activity
+namespace: molecular_function
+def: "Catalysis of the reaction: acetaldehyde + NADP+ + H2O = acetate + NADPH + 2 H+." [PMID:15659684, PMID:9473035, RHEA:25298]
+xref: RHEA:25298
+is_a: GO:0033721 ! aldehyde dehydrogenase (NADP+) activity
+property_value: term_tracker_item "#29544" xsd:anyURI
+created_by: pg
+creation_date: 2025-01-28T07:28:10Z

[pgaudet]

@ValWood

The annotation guidelines (and GO principles in general) state that the NAD(P) form should only be used if the H acceptor is not known; if it can use both, we should co-annotate.

So I'd prefer to create the grouping term aldehyde dehydrogenase [NAD(P)+] activity, since it's not needed for now.

OK ?

Thanks, Pascale

[sjm41]

Hi @pgaudet

Just checking you saw this comment above (I don't recall if the QC checks will catch this):

RHEA:25294 is currently a narrow xref on the parent term GO:0004029 you mention, so we could remove that and create the new child term.

[ValWood]

That's the problem. I have 2 paralogs in pombe. There are 4 paralogs in S. cerevisiae. These are independent duplications after speciation.
I don't know the specificities of either of the acetaldehyde dehydrogenase's, they could be one, or the other or both.
Maybe I am being too conservative if these enzymes may all be promiscuous to come degree? I just don't know. If you think it is safe, I will co-annotate to both terms.

Ignore it; I think it's fine to use NAD+ because that's the output from the previous reaction.

[pgaudet]

I though this is what I did

+[Term]
+id: GO:0140087
+name: acetaldehyde dehydrogenase (NAD+) activity
+namespace: molecular_function
+def: "Catalysis of the reaction: acetaldehyde + NAD+ + H2O = acetate + NADH + 2 H+." [PMID:9473035, RHEA:25294]
+xref: RHEA:25294
+is_a: GO:0004029 ! aldehyde dehydrogenase (NAD+) activity
+property_value: term_tracker_item "#29544" xsd:anyURI
+created_by: pg
+creation_date: 2025-01-28T07:26:40Z

Let me know if I made a mistake.

Thanks, Pascale

[sjm41]

New term looks good, I was just checking if you'd also removed RHEA:25294 from the parent term GO:0004029 ?

[pgaudet]

Yes, thanks for checking !