hydroxypyruvate reductase activity/glycerate dehydrogenase activity

[sjm41]

Looking at these two terms:

oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor
    |_hydroxypyruvate reductase activity
    |_glycerate dehydrogenase activity

Despite their different names, these represent the same activity and only differ in their use of NAD/NADP as the acceptor:

id: GO:0016618 name: hydroxypyruvate reductase activity namespace: molecular_function def: "Catalysis of the reaction: D-glycerate + NADP+ = hydroxypyruvate + NADPH + H+." [EC:1.1.1.81] synonym: "beta-hydroxypyruvate reductase activity" RELATED [EC:1.1.1.81] synonym: "D-glycerate dehydrogenase activity" RELATED [EC:1.1.1.81] synonym: "D-glycerate:NADP+ 2-oxidoreductase activity" RELATED [EC:1.1.1.81] synonym: "NADH:hydroxypyruvate reductase activity" RELATED [EC:1.1.1.81] xref: EC:1.1.1.81 xref: MetaCyc:HYDROXYPYRUVATE-REDUCTASE-RXN xref: MetaCyc:RXN0-300 xref: RHEA:18657 is_a: GO:0016616 ! oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor

id: GO:0008465 name: glycerate dehydrogenase activity namespace: molecular_function def: "Catalysis of the reaction: (R)-glycerate + NAD+ = hydroxypyruvate + NADH + H+." [EC:1.1.1.29] synonym: "hydroxypyruvate dehydrogenase activity" BROAD [EC:1.1.1.29] xref: EC:1.1.1.29 xref: MetaCyc:GLYCERATE-DEHYDROGENASE-RXN xref: RHEA:17905 is_a: GO:0016616 ! oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor

That's fine in itself, but EC actually says that EC:1.1.1.81 (GO:0016618) can use either NAD/NADP and also differs from the GO def in a couple of other ways (https://enzyme.expasy.org/EC/1.1.1.81).

So, I think the tasks here are:

hydroxypyruvate reductase activity (GO:0016618)

• [x] Change D-glycerate to R-glycerate in the def
• [x] Change hydroxypyruvate to 3-hydroxypyruvate in the def
• [x] Change NADP to NAD(P) in the def
• [x] Change name to 'hydroxypyruvate reductase (NAD(P)) activity'?
• [x] Remove RHEA:18657 xref (as this is specific to NADP version)
• [x] Remove MetaCyc:RXN0-300 xref (also specific to NADP version)

glycerate dehydrogenase activity (GO:0008465)

• [x] Change hydroxypyruvate to 3-hydroxypyruvate in the def
• [x] make this a child of hydroxypyruvate reductase activity (GO:0016618)
• [x] change name to glycerate dehydrogenase (NAD) activity?

hydroxypyruvate reductase (NADP) activity (NTR)

• [x] def: "Catalysis of the reaction: (R)-glycerate + NADP+ = 3-hydroxypyruvate + NADPH + H+." [RHEA:18657]
• [x] add RHEA:18657 & MetaCyc:RXN0-300 as xrefs
• [x] child of hydroxypyruvate reductase activity (GO:0016618)

Final tree would look like:

oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor
    |_hydroxypyruvate reductase (NAD(P)) activity
        |_glycerate dehydrogenase (NAD) activity
        |_hydroxypyruvate reductase (NADP) activity

[pgaudet]

Hi @sjm41

I have many questions:

• Why did you make glycerate dehydrogenase activity (GO:0008465) a child of hydroxypyruvate reductase activity (GO:0016618)? (the chemistry is not obvious to me)
• I think 'hydroxypyruvate reductase [NAD(P)] activity'(GO:0016618) should have either [NAD(P)+] or [NAD(P)H], but not nothing?
• in the screenshot above, I am not sure why none of the terms are the same WRT to the H+/H next to NAD/P
• More generally, I have been wondering whether we should add (NAD/P) in the term labels consistently, even if EC doesn't (I cannot figure out what their rules are for adding the NAD/P in the label or not.

Thanks, Pascale

[deustp01]

Is RHEA:17905 relevant here?

[pgaudet]

• I now see that EC https://enzyme.expasy.org/EC/1.1.1.81 (corresponding to ) has synonym: D-glycerate dehydrogenase but should we not use 'hydroxypyruvate' for all terms in that brach, for consistency?

• For RHEA:17905: maybe it should be the defxref for glycerate dehydrogenase (NAD+) activity? Rather than the EC?

[sjm41]

hydroxypyruvate reductase activity (GO:0016618) is EC:1.1.1.81: (R)-glycerate + NAD(P)+ = 3-hydroxypyruvate + H+ + NAD(P)H

glycerate dehydrogenase activity (GO:0008465) is EC:1.1.1.29 (RHEA:17905): (R)-glycerate + NAD(+) <=> 3-hydroxypyruvate + H(+) + NADH

So, the second reaction is the NAD-specific version of the first reaction.

The confusing thing is the EC names (which were inherited as GO term names), which represent opposite directions and which don't mention the NAD specificity:

• GO:0016618/EC:1.1.1.81 is "hydroxypyruvate reductase" (i.e. right to left)
• GO:0008465/EC:1.1.1.29 is "glycerate dehydrogenase" (i.e. left to right)

We didn't previously have the NADP-specific version (it's not in EC, but is RHEA:18657, which has >2,000 UP annotations), so I added that as "hydroxypyruvate reductase (NADPH) activity (GO:0120509)"

After several edits, I ended up with this:

hydroxypyruvate reductase [NAD(P)] activity (GO:0016618) [EC:1.1.1.81]
    |_glycerate dehydrogenase (NAD+) activity (GO:0008465) [EC:1.1.1.29/RHEA:17905]
    |_hydroxypyruvate reductase (NADPH) activity (GO:0120509) [RHEA:18657]

I can see that preserving the EC names here is confusing/inconsistent in the tree (and for the NAD labels), so we could certainly change that as an exceptional case where we don't use EC enzyme names. I will go ahead and use the 'hydroxypyruvate reductase' label for all.

Yes, I also see I messed up with the NAD bit in the GO:0016618 name - that should have been "hydroxypyruvate reductase [NAD(P)H] activity". Sorry about that - I will fix.

[sjm41]

More generally, I have been wondering whether we should add (NAD/P) in the term labels consistently, even if EC doesn't

I've also been wondering about that recently! I'll add the issue to our list....

[sjm41]

New version:

hydroxypyruvate reductase [NAD(P)H] activity (GO:0016618) [EC:1.1.1.81]
    |_hydroxypyruvate reductase (NADH) activity (GO:0008465) [EC:1.1.1.29/RHEA:17905]
    |_hydroxypyruvate reductase (NADPH) activity (GO:0120509) [RHEA:18657]