Closed sjm41 closed 5 months ago
Hi @sjm41
I have many questions:
Thanks, Pascale
Is RHEA:17905 relevant here?
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?
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:
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.
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....
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]
Looking at these two terms:
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)
glycerate dehydrogenase activity (GO:0008465)
hydroxypyruvate reductase (NADP) activity (NTR)
Final tree would look like: