Refine GPR annotation for Glycolysis pathway

[feiranl]

Description of the issue:

Enzyme	rxn	GPT result	GPT reason	Action
ENSG00000198099	MAR03905: ethanol[c] + NAD+[c] = acetaldehyde[c] + H+[c] + NADH[c]	No	The substrates are all-trans-retinol, 9-cis-retinol, long chain omega-hydroxy fatty acids, 20-HETE, 20-oxoarachidonate, and (5Z,8Z,11Z,14Z)-eicosatetraenedioate.	Rhea:21284;42052;39803;39799;60660
ENSG00000184254	MAR04283: acetaldehyde[c] + H2O[c] + NADP+[c] = acetate[c] + 2 H+[c] + NADPH[c]	No	Catalyzing the formation of retinoic acid from all-trans retinal	Rhea:42080
ENSG00000147576	MAR03905: ethanol[c] + NAD+[c] = acetaldehyde[c] + H+[c] + NADH[c]	No	The substrates are gamma-hydroxybutyrate (GHB), succinic semialdehyde (SSA), 2-ketoglutarate (2-KG), D-2-hydroxyglutarate (D-2-HG), D,L-3-hydroxyisobutyrate and L-3-hydroxybutyrate (L-3-OHB).	Rhea:23048
ENSG00000143149	MAR08357: acetaldehyde[m] + H2O[m] + NAD+[m] = acetate[m] + 2 H+[m] + NADH[m]	Yes	Yes, the substrates and products of this enzyme cover acetaldehyde, acetate, H+, H2O, NAD+, NADH. This enzyme catalyzes the irreversible oxidation of a broad range of aldehydes to the corresponding acids in an NAD-dependent reaction, which includes acetaldehyde being converted into acetate, and NAD+ being reduced to NADH.	Rhea:17985;19105
ENSG00000132746	MAR04283: acetaldehyde[c] + H2O[c] + NADP+[c] = acetate[c] + 2 H+[c] + NADPH[c]	No	No, the substrates and products of this enzyme do not cover the given metabolites. This enzyme specifically oxidizes medium and long chain aldehydes into non-toxic fatty acids, so the only metabolites it covers are aldehydes.	remove the gene
ENSG00000180011	MAR03905: ethanol[c] + NAD+[c] = acetaldehyde[c] + H+[c] + NADH[c]	No	No, the substrates and products of this enzyme do not cover the metabolites given (acetaldehyde, ethanol, H+, NAD+, NADH). This enzyme functions as a 15-oxo-prostaglandin 13-reductase and acts on 15-keto-PGE1, 15-keto-PGE2, 15-keto-PGE1-alpha and 15-keto-PGE2-alpha with highest efficiency towards 15-keto-PGE2-alpha, but not on acetaldehyde, ethanol, H+, NAD+, NADH.	Rhea:11912
ENSG00000180011	MAR04360: H2O[c] + methylglyoxal[c] + NADP+[c] = 2 H+[c] + NADPH[c] + pyruvate[c]	No	No, the substrates and products of this enzyme do not cover metabolites given: H+, H2O, methylglyoxal, NADP+, NADPH, pyruvate. The enzyme functions as 15-oxo-prostaglandin 13-reductase, with substrates and products being 15-keto-PGE1, 15-keto-PGE2, 15-keto-PGE1-alpha, 15-keto-PGE2-alpha, and NADPH.	Rhea:11912
ENSG00000131482	MAR08652: carbamoyl-phosphate[r] + glucose[r] = CO2[r] + glucose-6-phosphate[r] + NH3[r]	No	No, the substrates and products of this enzyme do not cover all of the metabolites given. The enzyme hydrolyzes glucose-6-phosphate to glucose, meaning the substrates and products of the enzyme are glucose-6-phosphate and glucose, not carbamoyl-phosphate, CO2, glucose, glucose-6-phosphate, and NH3.	Rhea:16689
ENSG00000130649	MAR08757: ethanol[c] + H+[c] + NADPH[c] + O2[c] = acetaldehyde[c] + 2 H2O[c] + NADP+[c]	No	No, the substrates and products of this enzyme do not cover the metabolites given: acetaldehyde, ethanol, H+, H2O, NADP+, NADPH, O2. This enzyme only catalyzes the hydroxylation of carbon-hydrogen bonds in fatty acids, and its substrates and products are fatty acids and oxygen, respectively.	Rhea:50076;39787;50088;39751;50096;26205
ENSG00000143891	MAR07745: beta-D-glucose[c] <= glucose[c]	No	No, the substrates and products of this enzyme do not cover metabolites beta-D-glucose and glucose, as the enzyme only catalyzes the interconversion of beta-D-galactose and alpha-D-galactose.	Rhea:28675;10264
ENSG00000141349	MAR08652: carbamoyl-phosphate[r] + glucose[r] = CO2[r] + glucose-6-phosphate[r] + NH3[r]	No	No, the substrates and products of this enzyme do not cover the given metabolites. The enzyme hydrolyzes glucose-6-phosphate to glucose, so the substrates and products are glucose-6-phosphate and glucose, not carbamoyl-phosphate, CO2, glucose, glucose-6-phosphate, and NH3.	Rhea:16689
ENSG00000006534	MAR04283: acetaldehyde[c] + H2O[c] + NADP+[c] = acetate[c] + 2 H+[c] + NADPH[c]	No	No, the substrates and products of this enzyme do not cover the metabolites given. This enzyme oxidizes medium and long chain saturated and unsaturated aldehydes, benzaldehyde, and can use both NADP(+) and NAD(+) as electron acceptor. It has low activity towards acetaldehyde and 3,4-dihydroxyphenylacetaldehyde, and may not metabolize short chain aldehydes. The metabolites given are acetaldehyde, acetate, H+, H2O, NADP+, NADPH, which are not covered by this enzyme.	Rhea: 33739;44100;59904; 21660;11840;59908;59912;59916;59920
ENSG00000197894	MAR03905: ethanol[c] + NAD+[c] = acetaldehyde[c] + H+[c] + NADH[c]	No	No, the substrates and products of this enzyme do not cover acetaldehyde, ethanol, H+, NAD+, NADH. This enzyme catalyzes the oxidation of long-chain primary alcohols and S-(hydroxymethyl) glutathione, as well as the oxidation of long-chain omega-hydroxy fatty acids, such as 20-HETE, producing both an intermediate aldehyde and a dicarboxylic acid. It does not catalyze the oxidation of ethanol and does not involve acetaldehyde, H+, NAD+, or NADH.	Rhea:19981;19985;39803;39799
ENSG00000072210	MAR08357: acetaldehyde[m] + H2O[m] + NAD+[m] = acetate[m] + 2 H+[m] + NADH[m]	No	No, the substrates and products of this enzyme do not cover acetaldehyde, acetate, H+, H2O, NAD+, NADH. This enzyme catalyzes the oxidation of medium and long chain aliphatic aldehydes to fatty acids, not acetaldehyde, acetate, H+, H2O, NAD+, NADH.	Rhea:36135;33739;39015;44016;44020;44168;44104;44172;44100;44108;24216
ENSG00000149925	MAR04355: DHAP[c] + erythrose-4-phosphate[c] = sedoheptulose-1,7-bisphosphate[c]	No	No, the substrates and products of this enzyme do not cover DHAP, erythrose-4-phosphate, and sedoheptulose-1,7-bisphosphate. This enzyme catalyzes the reversible conversion of beta-D-fructose 1,6-bisphosphate (FBP) into two triose phosphates, which does not include DHAP, erythrose-4-phosphate, and sedoheptulose-1,7-bisphosphate as metabolites.	remove the gene
ENSG00000154305	MAR04368: 1,3-bisphospho-D-glycerate[c] + ADP[c] <= 3-phospho-D-glycerate[c] + ATP[c]	No	No, the substrates and products of this enzyme do not cover the metabolites 1,3-bisphospho-D-glycerate, 3-phospho-D-glycerate, ADP, and ATP. This enzyme is responsible for transporting large cargos like collagen VII, lipoproteins, and COPII coat components, but does not directly interact with the above metabolites.	involve in ER transportation, remove the gene from HumanGEM
ENSG00000166800	MAR04281: H+[x] + NADH[x] + pyruvate[x] <= L-lactate[x] + NAD+[x]	Yes	Yes, the substrates and products of this enzyme cover the given metabolites: H+, L-lactate, NAD+, NADH, pyruvate. This is because the enzyme catalyzes the interconversion of L-lactate and pyruvate with NAD+ as a coenzyme. Therefore, these metabolites are all part of the reaction catalyzed by the enzyme.	remove the gene, not x annotation
ENSG00000121691	MAR08360: ethanol[x] + H2O2[x] = acetaldehyde[x] + 2 H2O[x]	No	No, the substrates and products of this enzyme do not cover metabolites given: acetaldehyde, ethanol, H2O, H2O2. This enzyme catalyzes the degradation of hydrogen peroxide (H2O2) to water and oxygen, and does not involve acetaldehyde, ethanol, H2O.	Rhea:20309
ENSG00000196616	MAR03905: ethanol[c] + NAD+[c] = acetaldehyde[c] + H+[c] + NADH[c]	No	No, the substrates and products of this enzyme do not cover the metabolites acetaldehyde, ethanol, H+, NAD+, NADH. This enzyme catalyzes the NAD-dependent oxidation of all-trans-retinol and its derivatives as well as the NADH-dependent reduction of all-trans-retinal and its derivatives.	Rhea:21284;55936; 60632

I hereby confirm that I have:

• Done this analysis in the main branch of the repository
• Checked that a similar issue does not exist already

[haowang-bioinfo]

@feiranl maybe clarify a bit the action column.

are those Rhea ids the reactions to be added?

[feiranl]

As for the gene with the action "Rhea:xxx", I will check wether the rxn exists or not, and then add the new rxn or expand the GPRs. As for the gene with the action "remove the gene", I will remove the gene from the GPR

[haowang-bioinfo]

As for the gene with the action "Rhea:xxx", I will check wether the rxn exists or not, and then add the new rxn or expand the GPRs.

the rxnRheaMasterID column in reactions.tsv was recently updated, it should help in deciding wether the rxn exists or not

[feiranl]

We will firstly fix the remove gene part. reaction addition part will be fixed later

[haowang-bioinfo]

fixed in #517 and #535