GPR curation for Pentose phosphate pathway, Pyruvate metabolism and Tricarboxylic acid cycle and glyoxylate/dicarboxylate metabolism

[JHL-452b]

Current behavior:

20 genes are discovered to be uncorrelated with their corresponding reactions in Pentose phosphate pathway, Pyruvate metabolism and Tricarboxylic acid cycle and glyoxylate/dicarboxylate metabolism

Gene	UniProtID	Reaction	GPR	Correlation	Manually check
ENSG00000152556	P08237	MAR04567: ATP + sedoheptulose-7-phosphate --> ADP + H+ + sedoheptulose-1,7-bisphosphate	ENSG00000067057 or ENSG00000141959 or ENSG00000152556	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000152556 encodes a protein that catalyzes the phosphorylation of D-fructose 6-phosphate to fructose 1,6-bisphosphate using ATP, a key step in glycolysis. The reaction provided involves ATP and sedoheptulose-7-phosphate, leading to the formation of ADP, H+, and sedoheptulose-1,7-bisphosphate, which is unrelated to the function and catalytic activity described for this gene.	No
ENSG00000165140	P09467	MAR20070: H2O + sedoheptulose-1,7-bisphosphate --> Pi + sedoheptulose-7-phosphate	ENSG00000130957 or ENSG00000165140	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000165140 catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate, which is a reaction specific to fructose metabolism. However, the reaction in question involves the hydrolysis of sedoheptulose-1,7-bisphosphate to sedoheptulose-7-phosphate, a distinct substrate and product not associated with the function of the gene described. Therefore, the gene does not have relevance to the reaction provided.	No
ENSG00000130957	O00757	MAR20070: H2O + sedoheptulose-1,7-bisphosphate --> Pi + sedoheptulose-7-phosphate	ENSG00000130957 or ENSG00000165140	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000130957 is annotated to catalyze the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate, which is involved in glycogen synthesis from carbohydrate precursors. However, the reaction provided involves the conversion of sedoheptulose-1,7-bisphosphate to sedoheptulose-7-phosphate and inorganic phosphate (Pi), a reaction that is different from the one this gene catalyzes. Therefore, the gene ENSG00000130957 is not related to the provided reaction.	No
ENSG00000138030	P50053	MAR09800: ATP + sedoheptulose <=> ADP + H+ + sedoheptulose-1-phosphate	ENSG00000138030	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000138030 encodes for an enzyme that catalyzes the phosphorylation of fructose to fructose-1-phosphate using ATP. However, the provided reaction involves ATP and sedoheptulose, resulting in the formation of ADP, H+, and sedoheptulose-1-phosphate, indicating a different substrate and product. Thus, the gene's function does not correspond to the reaction involving sedoheptulose.	No
ENSG00000130313	O95336	MAR08653: glucono-1,5-lactone-6-phosphate + H+ + NADH <=> glucose-6-phosphate + NAD+	ENSG00000049239 or ENSG00000130313	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000130313 codes for an enzyme that catalyzes the hydrolysis of 6-phosphogluconolactone to 6-phosphogluconate, with the specific reaction being 6-phospho-D-glucono-1,5-lactone + H2O = 6-phospho-D-gluconate + H(+). The given reaction involving glucono-1,5-lactone-6-phosphate, H+, NADH, glucose-6-phosphate, and NAD+ does not match the enzymatic activity or catalytic function described for this gene. The provided gene annotations do not indicate involvement in the given reaction.	No
ENSG00000182224	Q6P9G0	MAR03859: D-lactate + 2.0 ferricytochrome C --> 2.0 ferrocytochrome C + 2.0 H+ + pyruvate	ENSG00000166816 or ENSG00000182224	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. The gene ENSG00000182224 is described as a radial spoke stalk protein involved in cilia function and redox signaling pathways. It does not exhibit any catalytic activity related to the reaction, which involves the conversion of D-lactate and ferricytochrome C to ferrocytochrome C, H+, and pyruvate. Therefore, the gene and the reaction are not related.	No
ENSG00000196616	P00325	MAR08502: (R)-S-lactoylglutathione + H+ + NADH <=> D-lactaldehyde + GSH + NAD+	ENSG00000147576 or ENSG00000172955 or ENSG00000187758 or ENSG00000196344 or ENSG00000196616 or ENSG00000197894 or ENSG00000198099 or ENSG00000248144	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000196616 encodes an enzyme that catalyzes the NAD-dependent oxidation of all-trans-retinol and its derivatives, participating in retinoid metabolism. The associated catalytic activities are specific to reactions involving all-trans-retinol, all-trans-4-hydroxyretinol, and all-trans-4-oxoretinol as substrates. Conversely, the provided reaction involves (R)-S-lactoylglutathione and NADH converting to D-lactaldehyde, GSH, and NAD+, which is not related to the enzymatic functions described for ENSG00000196616. Hence, the gene and the reaction are not related.	No
ENSG00000184254	P47895	MAR08503: H2O + lactaldehyde + NAD+ --> 2.0 H+ + L-lactate + NADH	ENSG00000006534 or ENSG00000072210 or ENSG00000108602 or ENSG00000132746 or ENSG00000143149 or ENSG00000164904 or ENSG00000184254	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. The gene ENSG00000184254 encodes an enzyme that catalyzes the oxidation of aldehyde substrates such as all-trans-retinal and all-trans-13,14-dihydroretinal to their corresponding carboxylic acids with high specificity. This gene's enzyme activity is related to the biosynthesis of retinoate, which is critical for embryonic development of the eye and nasal region. However, the provided reaction (H2O + lactaldehyde + NAD+ --> 2.0 H+ + L-lactate + NADH) involves the conversion of lactaldehyde to L-lactate, which is not described as a substrate or product of the enzyme encoded by this gene. Therefore, the gene is not relevant to the provided reaction.	No
ENSG00000198099	P08319	MAR08507: NAD+ + propane-1,2-diol --> D-lactaldehyde + H+ + NADH	ENSG00000147576 or ENSG00000172955 or ENSG00000180011 or ENSG00000187758 or ENSG00000196344 or ENSG00000196616 or ENSG00000197894 or ENSG00000198099 or ENSG00000248144	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000198099 encodes a protein that catalyzes the NAD-dependent oxidation of all-trans-retinol, 9-cis-retinol, long chain omega-hydroxy fatty acids, and the reduction of benzoquinones. The reactions include the conversion of all-trans-retinol to all-trans-retinal, 9-cis-retinol to 9-cis-retinal, 20-hydroxy-eicosatetraenoate to 20-oxo-eicosatetraenoate, and benzoquinone to hydroquinone. However, the provided reaction involves the conversion of NAD+ and propane-1,2-diol to D-lactaldehyde, which is not among the reactions catalyzed by the protein encoded by this gene as per the provided annotations.	No Yes
ENSG00000180011	Q8N4Q0	MAR08507: NAD+ + propane-1,2-diol --> D-lactaldehyde + H+ + NADH	ENSG00000147576 or ENSG00000172955 or ENSG00000180011 or ENSG00000187758 or ENSG00000196344 or ENSG00000196616 or ENSG00000197894 or ENSG00000198099 or ENSG00000248144	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000180011 encodes a protein that functions as a 15-oxo-prostaglandin 13-reductase, acting specifically on various 15-keto prostaglandins using NADP(+) as a cofactor, resulting in the production of NADPH. The reactions listed in the gene's annotation are related to prostaglandin metabolism, involving substrates like 15-oxo-PGE1, 15-oxo-PGE2, and similar compounds. However, the reaction provided involves NAD+ and propane-1,2-diol yielding D-lactaldehyde and NADH, which are unrelated to prostaglandin metabolism or the activities described for the gene ENSG00000180011. Therefore, the gene is not relevant to the given reaction.	No Yes
ENSG00000196616	P00325	MAR08508: NAD+ + propane-1,2-diol --> H+ + lactaldehyde + NADH	ENSG00000147576 or ENSG00000172955 or ENSG00000180011 or ENSG00000187758 or ENSG00000196344 or ENSG00000196616 or ENSG00000197894 or ENSG00000198099 or ENSG00000248144	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000196616 encodes an enzyme that catalyzes the NAD-dependent oxidation of all-trans-retinol and its derivatives, participating in retinoid metabolism. The catalytic activities described involve reactions with retinol derivatives, not propane-1,2-diol. The provided reaction, which converts NAD+ and propane-1,2-diol to H+, lactaldehyde, and NADH, does not involve the retinoid metabolism pathway and substrates specific to the gene. Hence, the gene and the reaction are not related.	No
ENSG00000166816	Q86WU2	MAR08514: 2.0 ferricytochrome C + L-lactate --> 2.0 ferrocytochrome C + 2.0 H+ + pyruvate	ENSG00000166816 or ENSG00000182224	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. The gene ENSG00000166816 is involved in the catabolic process of D-lactate, whereas the reaction provided involves the conversion of L-lactate with ferricytochrome C, producing ferrocytochrome C, hydrogen ions, and pyruvate. Therefore, the gene's function does not align with the reaction specified.	No
ENSG00000148090	Q13825	MAR08516: DHAP --> methylglyoxal + Pi	ENSG00000148090	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000148090 encodes an enzyme involved in the leucine degradation pathway and catalyzes reactions such as the conversion of 3-methylglutaconyl-CoA to 3-hydroxy-3-methylglutaryl-CoA, amongst others. However, the provided reaction "DHAP --> methylglyoxal + Pi" is not related to any of the enzymatic activities described for this gene. The gene's annotated function does not include catalyzing the conversion of DHAP (dihydroxyacetone phosphate) to methylglyoxal and phosphate, indicating the gene and the reaction are not related.	No, it's a spontaneous reaction
ENSG00000059573	P54886	MAR01474: D-lactaldehyde + H2O + NAD+ --> D-lactate + 2.0 H+ + NADH	ENSG00000059573 or ENSG00000111275 or ENSG00000112294 or ENSG00000119711 or ENSG00000137124 or ENSG00000159423	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000059573 encodes a bifunctional enzyme involved in converting glutamate to glutamate 5-semialdehyde, playing a role in the biosynthesis of proline, ornithine, and arginine. The gene's catalytic activities are specific to reactions involving glutamate, glutamyl 5-phosphate, and associated intermediates. In contrast, the provided reaction involves D-lactaldehyde, NAD+, and the production of D-lactate, which does not intersect with the pathways or substrates associated with ENSG00000059573. Therefore, there is no relevance between the gene and the provided reaction.	No Yes
ENSG00000164904	P49419	MAR08503: H2O + lactaldehyde + NAD+ --> 2.0 H+ + L-lactate + NADH	ENSG00000006534 or ENSG00000072210 or ENSG00000108602 or ENSG00000132746 or ENSG00000143149 or ENSG00000164904 or ENSG00000184254	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. The gene ENSG00000164904 encodes an enzyme that metabolizes various aldehydes into their corresponding carboxylates using NAD+ as a cofactor. The specific reactions listed in the annotation involve the oxidation of betaine aldehyde to glycine betaine, nonanal to nonanoate, (S)-2-amino-6-oxohexanoate to L-2-aminoadipate, and others, none of which include the conversion of lactaldehyde to L-lactate. Therefore, the provided reaction involving lactaldehyde does not match any of the activities of the gene product.	No Yes
ENSG00000116882	Q9NYQ3	MAR07704: FAD + glyoxalate + H2O --> FADH2 + H+ + oxalate	ENSG00000101323 or ENSG00000116882	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The functions and catalytic activities of the gene ENSG00000116882 involve catalyzing the oxidation of medium and long chain hydroxyacids such as 2-hydroxyhexadecanoate and 2-hydroxyoctanoate to 2-oxoacids, with the production of H2O2. However, this gene is not active on glyoxylate and does not catalyze the reaction FAD + glyoxalate + H2O ¡ú FADH2 + H+ + oxalate. Therefore, the gene is not relevant to the reaction provided.	No
ENSG00000116882	Q9NYQ3	MAR07706: FAD + glycolate --> FADH2 + glyoxalate	ENSG00000101323 or ENSG00000116882	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. The gene ENSG00000116882 encodes an oxidase that catalyzes the oxidation of medium and long chain hydroxyacids, specifically 2-hydroxyhexadecanoate and 2-hydroxyoctanoate, to their corresponding 2-oxoacids. It is not active on substrates such as glycolate, as mentioned in the information. The provided reaction, which involves the conversion of glycolate to glyoxalate, does not match the specificity or activity described for the gene product. Hence, the reaction is unrelated to the gene's function.	No
ENSG00000184254	P47895	MAR08775: glycolaldehyde + H2O + NAD+ --> glycolate + 2.0 H+ + NADH	ENSG00000006534 or ENSG00000072210 or ENSG00000108602 or ENSG00000132746 or ENSG00000143149 or ENSG00000164904 or ENSG00000184254	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000184254 encodes an enzyme that catalyzes the NAD-dependent oxidation of aldehyde substrates such as all-trans-retinal and all-trans-13,14-dihydroretinal to their corresponding carboxylic acids. The reactions this enzyme is involved in are specifically related to the metabolism of retinal and retinoate compounds. However, the provided reaction ("glycolaldehyde + H2O + NAD+ --> glycolate + 2.0 H+ + NADH") involves the oxidation of glycolaldehyde to glycolate. There is no indication from the provided information that the gene product has activity on glycolaldehyde or any similar substrate, thus it is not relevant to the specified reaction.	No
ENSG00000149925	P04075	MAR08773: D-xylulose-1-phosphate <=> DHAP + glycolaldehyde	ENSG00000109107 or ENSG00000136872 or ENSG00000149925	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. Based on the annotation of the gene ENSG00000149925, its function is to catalyze the reversible conversion of beta-D-fructose 1,6-bisphosphate into D-glyceraldehyde 3-phosphate and dihydroxyacetone phosphate, which is a key reaction in glycolysis and gluconeogenesis. However, the reaction provided involves D-xylulose-1-phosphate converting to DHAP and glycolaldehyde, which is not related to the substrate or products of the gene's annotated catalytic activity. Therefore, the gene is not relevant to this reaction.	No Yes
ENSG00000072210	P51648	MAR08778: glycolaldehyde + H2O + NAD+ --> glycolate + 2.0 H+ + NADH	ENSG00000072210 or ENSG00000111275 or ENSG00000137124 or ENSG00000143149 or ENSG00000164904	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. The gene ENSG00000072210 encodes for an enzyme that catalyzes the oxidation of medium and long chain aliphatic aldehydes to fatty acids. The enzyme is active on a variety of saturated and unsaturated aliphatic aldehydes between 6 and 24 carbons in length and is responsible for the conversion of the sphingosine 1-phosphate degradation product hexadecenal to hexadecenoic acid. The specific reaction provided involves the oxidation of glycolaldehyde, a small two-carbon molecule, which falls outside the range of the aliphatic aldehydes targeted by the gene's enzyme. Therefore, the gene and the reaction are not related.	No

[JHL-452b]

For these subsytems, I continued to add 4 unrelated gene-reaction pairs discoverd by GPT.

Gene	UniProtID	Reaction	GPR	Correlation	Check
ENSG00000141959	P17858	MAR04567: ATP + sedoheptulose-7-phosphate --> ADP + H+ + sedoheptulose-1,7-bisphosphate	ENSG00000067057 or ENSG00000141959 or ENSG00000152556	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. The gene ENSG00000141959 catalyzes the phosphorylation of D-fructose 6-phosphate to fructose 1,6-bisphosphate using ATP. However, the reaction provided is the phosphorylation of sedoheptulose-7-phosphate to sedoheptulose-1,7-bisphosphate using ATP. These are different substrates and reactions, and hence the gene is not relevant to the reaction provided.	No Yes
ENSG00000196616	P00325	MAR08507: NAD+ + propane-1,2-diol --> D-lactaldehyde + H+ + NADH	ENSG00000147576 or ENSG00000172955 or ENSG00000180011 or ENSG00000187758 or ENSG00000196344 or ENSG00000196616 or ENSG00000197894 or ENSG00000198099 or ENSG00000248144	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000196616 is annotated to catalyze reactions involving all-trans-retinol and its derivatives in the presence of NAD+, leading to all-trans-retinal and its derivatives. However, the provided reaction involves the conversion of propane-1,2-diol to D-lactaldehyde, which does not involve retinoids or similar substrates. Therefore, the substrates and products in the provided reaction do not match those associated with the gene's annotated catalytic activities, indicating no relevance.	No
ENSG00000180011	Q8N4Q0	MAR08508: NAD+ + propane-1,2-diol --> H+ + lactaldehyde + NADH	ENSG00000147576 or ENSG00000172955 or ENSG00000180011 or ENSG00000187758 or ENSG00000196344 or ENSG00000196616 or ENSG00000197894 or ENSG00000198099 or ENSG00000248144	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. The gene ENSG00000180011 is associated with the catalytic activity involving 15-oxo-prostaglandins and utilizes NADP+ as a cofactor. It specifically acts on various forms of 15-keto-prostaglandins, resulting in their reduction. The provided reaction, however, involves NAD+ and converts propane-1,2-diol into lactaldehyde. This reaction is unrelated to the enzymatic functions of the gene, which does not act on propane-1,2-diol or involve NAD+ as a cofactor.	No Yes
ENSG00000072210	P51648	MAR08506: H2O + lactaldehyde + NAD+ --> 2.0 H+ + L-lactate + NADH	ENSG00000072210 or ENSG00000111275 or ENSG00000137124 or ENSG00000143149 or ENSG00000164904	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000072210 encodes an enzyme that catalyzes the oxidation of various medium and long-chain aliphatic aldehydes to fatty acids, using NAD+ as a cofactor. However, the provided reaction converts lactaldehyde to L-lactate, which does not correspond to the aliphatic aldehydes mentioned in the gene's function. Therefore, the specific aldehyde and product in the reaction do not align with the substrate specificity or catalytic activity described for the gene.	No

[feiranl]

Suggestions:
Keep ENSG00000180011 for MAR08507, ENSG00000198099 for MAR08507, ENSG00000059573 for MAR01474, ENSG00000164904 for MAR08503, ENSG00000149925 for MAR08773, ENSG00000141959 for MAR04567, and ENSG00000180011 for MAR08508 for their enzyme promiscuity.

While removing the gene ENSG00000148090 for MAR08516, keep the reaction, as it can occur as a spontaneous reaction in humans (PMID: 25709564).

[feiranl]

Good example for Human2 manuscript: ENSG00000182224 for MAR03859, since ENSG00000182224 is not known to catalyze the conversion of D-lactate to pyruvate. CYB5D1 is primarily involved in electron transfer processes and is related to cytochrome b5, which generally plays roles in redox reactions within the electron transport chain, lipid metabolism, and drug metabolism. ENSG00000116882 for MAR07704, since ENSG00000116882 is not active on glycolate, glyoxylate, L-lactate, and 2-hydroxybutanoate (PubMed: 10777549).