New child terms of alcohol dehydrogenase (NAD+) activity (GO:0004022)

[sjm41]

The following terms are currently direct children of "oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor (GO:0016616)" but should be moved to be direct children of the more specific term: alcohol dehydrogenase (NAD+) activity (GO:0004022) Def:Catalysis of the reaction: an alcohol + NAD+ = an aldehyde or ketone + NADH + H+.[ EC:1 ]

This fits with their relationships in RHEA (see https://www.rhea-db.org/rhea/10736)

id: GO:0004552 name: octanol dehydrogenase activity RHEA:24620 NAD+ + octan-1-ol = H+ + NADH + octanal

id: GO:0047978 name: hexadecanol dehydrogenase activity RHEA:22056 hexadecan-1-ol + NAD+ = H+ + hexadecanal + NADH

id: GO:0004745 name: NAD-retinol dehydrogenase activity RHEA:21284 all-trans-retinol + NAD+ = all-trans-retinal + H+ + NADH

id: GO:0050093 name: methanol dehydrogenase activity RHEA:19401 methanol + NAD+ = formaldehyde + H+ + NADH

id: GO:0047018 name: indole-3-acetaldehyde reductase (NADH) activity RHEA:14873 indole-3-ethanol + NAD+ = H+ + indole-3-acetaldehyde + NADH

id: GO:0018456 name: aryl-alcohol dehydrogenase (NAD+) activity RHEA:12076 an aromatic primary alcohol + NAD+ = an aromatic aldehyde + H+ + NADH

id: GO:0018457 name: perillyl-alcohol dehydrogenase activity RHEA:10664 NAD+ + perillyl alcohol = H+ + NADH + perillyl aldehyde

(This list isn't exhaustive - there may be other, similar cases)

[pgaudet]

Thanks @sjm41 For consistency: should we add 'NAD+' in the term label? For example as in ''L-xylulose reductase (NAD+) activity' (note that we are also inconsistent about that, sometimes it says 'NAD+-dependent)

Thanks, Pascale

[sjm41]

Hi @pgaudet Sure, adding '(NAD+)' to the name makes sense to me. Another consistency question - are we consistent if we write (NAD+), (NAD) or (NADH) in these cases?

[pgaudet]

oh gosh! we are quite inconsistent.

I can only find these 4 using NAD:

• 'valine dehydrogenase (NAD) activity' http://purl.obolibrary.org/obo/GO_0043837
• 'D-xylose 1-dehydrogenase (NAD) activity' http://purl.obolibrary.org/obo/GO_0047838
• 'aryl-aldehyde dehydrogenase (NAD) activity' http://purl.obolibrary.org/obo/GO_0019108
• '(3R)-hydroxyacyl-CoA dehydrogenase (NAD) activity' http://purl.obolibrary.org/obo/GO_0106386 but for NAD+ versus NADH we have 36 and 18, repectively.

Based on the definition it seems like NAD+ would be right, is this also your conclusion?

[sjm41]

Based on the definition it seems like NAD+ would be right, is this also your conclusion?

Well, given the GO reactions are (almost) always given with an undefined reaction direction, you could say that these reactions are either "NAD+" or "NADH"-dependent. That is, they are NAD+-dependent in one direction, and NADH-dependent in the other direction. So I think we just need to make a decision on GO policy/convention here and then be consistent.

The current guidelines (https://wiki.geneontology.org/Guidelines_for_new_Molecular_Functions#NAD/NADP_cofactors) aren't explicit about this point, though they suggest that "NAD" (and "NADP") is the preferred usage, even though that's currently used in only 4 terms? Using just 'NAD' gets around the problem that reactions are either NAD+/NADH-dependent, depending on which direction you're looking at....

[sjm41]

Also, just noting that for GO grouping terms, we seem to just use 'NAD/NADP', for example: oxidoreductase activity, acting on the aldehyde or oxo group of donors, NAD or NADP as acceptor (GO:0016620) oxidoreductase activity, acting on the CH-CH group of donors, NAD or NADP as acceptor (GO:0016628) oxidoreductase activity, acting on metal ions, NAD or NADP as acceptor (GO:0016723)

[pgaudet]

Right, this is copied from EC, see for example here: https://enzyme.expasy.org/EC/1.2.1.-

I would keep our alignment with EC for the grouping class labels.

[sjm41]

But the EC description in that example is different from GO: EC:1.2.1.- is "With NAD(+) or NADP(+) as acceptor", whereas the corresponding GO term has "...NAD or NADP as acceptor". So GO has removed the "(+)" in these cases.

So...we could decide to align with EC in our labels (for grouping classes and leaf terms), which I think means GO would consistently use "NAD+" and NADP+"? or We could decide to consistently do what we already do for GO grouping terms, and consistently use "NAD" and "NADP"?

[pgaudet]

oh yes yes, - I though you were refering to the parenthesis around the NAD/NADH.

NAD+ / NADP+ seems the most consistent with how we label other chemicals (we have removed all parenthesis around H(+) as well, for instance, to use H+).

WRT directionality: For example we have 'GO:0052874 FMN reductase (NADH) activity' >> definition = Catalysis of the reaction: FMNH2 + NAD+ = FMN + NADH + 2 H+.

So, NAD+ would be more appropriate in the label? But our label and definitions match EC: https://enzyme.expasy.org/EC/1.5.1.42

I am not sure what you mean by

Using just 'NAD' gets around the problem that reactions are either NAD+/NADH-dependent, depending on which direction you're looking at....

you would put NAD on both sides?

[sjm41]

I realise now that I was overlooking an important point in my previous comments: yes, the definition of these oxidoreductase GO terms is (nearly) always non-directional, but the the term names are necessarily directional - ie. term names are like "[substrate] dehydrogenase" or "[substrate] reductase". It therefore makes complete sense to specify NADH/NAD+ or NADPH/NADP+ in the term names, and to mirror the EC names in this regard (whenever available). From that point of view, it also makes sense that the grouping terms (e.g. "oxidoreductase activity, acting on metal ions, NAD or NADP as acceptor") only say 'NAD/NADP' as those grouping term names really are non-directional.

So, I will:

1. Go ahead with the 7 new parent-child relationships proposed at the top of this ticket.
2. Add ('NAD+)' to the names of those 7 terms in cases where it's currently missing.
3. Make a separate ticket to clean-up and fix other term labels where only 'NAD' or 'NADP' is specified, or where we use a different format (e.g. 'NADH-dependent'), or where the term label has NADH when it should be NAD+ (etc) - I just checked, and found several such cases.

[sjm41]

I also updated a few other term names and relationships under 'alcohol dehydrogenase (NAD+) activity' and 'alcohol dehydrogenase (NADP+) activity'

[deustp01]

the definition of these oxidoreductase GO terms is (nearly) always non-directional, but the the term names are necessarily directional

A tangential thought. This can be generalized - aldolase - and, worse, the name can be backwards - pyruvate kinase. For human usability, I expect GO needs to respect accepted names, and capture the physiological reaction details only in the definition, with clauses and comments as needed to flag cases where physiology and nomenclature diverge.