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SysBioChalmers / Human-GEM

The generic genome-scale metabolic model of Homo sapiens
https://sysbiochalmers.github.io/Human-GEM-guide/
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GPR curation for Arachidonic acid metabolism (1) #853

Open JHL-452b opened 2 months ago

JHL-452b commented 2 months ago

Current behavior:

27 genes are discovered to be uncorrelated with their corresponding reactions in Arachidonic acid metabolism

Gene UniProtID Reaction GPR Correlation Manually check
ENSG00000137869 P11511 MAR00931: arachidonate + H+ + NADPH + O2 --> 7-HETE + H2O + NADP+ ENSG00000021461 or ENSG00000100197 or ENSG00000106258 or ENSG00000108242 or ENSG00000130649 or ENSG00000134716 or ENSG00000137869 or ENSG00000138061 or ENSG00000138109 or ENSG00000138115 or ENSG00000140465 or ENSG00000140505 or ENSG00000142973 or ENSG00000155016 or ENSG00000160868 or ENSG00000160870 or ENSG00000165841 or ENSG00000167600 or ENSG00000171903 or ENSG00000186160 or ENSG00000186204 or ENSG00000186377 or ENSG00000186526 or ENSG00000197408 or ENSG00000197446 or ENSG00000197838 or ENSG00000198077 or ENSG00000255974 Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000137869 encodes a cytochrome P450 monooxygenase, which catalyzes the conversion of C19 androgens to C18 estrogens and exhibits specific activities such as 2-hydroxylase activity toward estrone. The described catalytic activities involve the use of molecular oxygen and NADPH in the conversion of androgens and estrogens through multiple oxidation steps. However, the reaction provided involves the conversion of arachidonate to 7-HETE using H+, NADPH, and O2, producing H2O and NADP+, which is not related to the androgen-to-estrogen conversion pathways or any other activities outlined for the gene¡¯s enzyme products. Therefore, there is no direct relevance between the gene ENSG00000137869 and the provided reaction. No
ENSG00000197408 P20813 MAR00932: arachidonate + H+ + NADPH + O2 --> 8-HETE + H2O + NADP+ ENSG00000021461 or ENSG00000100197 or ENSG00000106258 or ENSG00000108242 or ENSG00000130649 or ENSG00000134716 or ENSG00000137869 or ENSG00000138061 or ENSG00000138109 or ENSG00000138115 or ENSG00000140465 or ENSG00000140505 or ENSG00000142973 or ENSG00000155016 or ENSG00000160868 or ENSG00000160870 or ENSG00000165841 or ENSG00000167600 or ENSG00000171903 or ENSG00000186160 or ENSG00000186204 or ENSG00000186377 or ENSG00000186526 or ENSG00000197408 or ENSG00000197446 or ENSG00000197838 or ENSG00000198077 or ENSG00000255974 Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. The gene ENSG00000197408 encodes a cytochrome P450 monooxygenase involved in the metabolism of endocannabinoids and steroids. Its known catalytic activities include the epoxidation of arachidonoylethanolamide (anandamide), hydroxylation of steroid hormones such as testosterone and estrogens, and the oxidation of xenobiotics like plant lipids and drugs. However, the reaction involving the conversion of arachidonate with NADPH and O2 into 8-HETE is not listed among the catalytic activities attributed to this gene. Therefore, the provided gene does not catalyze or have any relevance to the given reaction. No
ENSG00000160870 P24462 MAR00932: arachidonate + H+ + NADPH + O2 --> 8-HETE + H2O + NADP+ ENSG00000021461 or ENSG00000100197 or ENSG00000106258 or ENSG00000108242 or ENSG00000130649 or ENSG00000134716 or ENSG00000137869 or ENSG00000138061 or ENSG00000138109 or ENSG00000138115 or ENSG00000140465 or ENSG00000140505 or ENSG00000142973 or ENSG00000155016 or ENSG00000160868 or ENSG00000160870 or ENSG00000165841 or ENSG00000167600 or ENSG00000171903 or ENSG00000186160 or ENSG00000186204 or ENSG00000186377 or ENSG00000186526 or ENSG00000197408 or ENSG00000197446 or ENSG00000197838 or ENSG00000198077 or ENSG00000255974 Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. The gene ENSG00000160870 encodes a cytochrome P450 monooxygenase involved in the metabolism of steroid hormones and vitamins, and the oxidative metabolism of xenobiotics. Its catalytic activities include hydroxylation of androgens, estrogens, and retinoic acids. However, the specific reaction provided involves the conversion of arachidonate to 8-HETE using NADPH and oxygen, which is not within the annotated functions or substrates of this gene. Hence, there is no direct connection between the gene's annotated activities and the provided reaction. No
ENSG00000137869 P11511 MAR00932: arachidonate + H+ + NADPH + O2 --> 8-HETE + H2O + NADP+ ENSG00000021461 or ENSG00000100197 or ENSG00000106258 or ENSG00000108242 or ENSG00000130649 or ENSG00000134716 or ENSG00000137869 or ENSG00000138061 or ENSG00000138109 or ENSG00000138115 or ENSG00000140465 or ENSG00000140505 or ENSG00000142973 or ENSG00000155016 or ENSG00000160868 or ENSG00000160870 or ENSG00000165841 or ENSG00000167600 or ENSG00000171903 or ENSG00000186160 or ENSG00000186204 or ENSG00000186377 or ENSG00000186526 or ENSG00000197408 or ENSG00000197446 or ENSG00000197838 or ENSG00000198077 or ENSG00000255974 Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000137869 encodes a cytochrome P450 monooxygenase which is involved in the oxidation of C19 androgens to C18 estrogens, the conversion of dihydrotestosterone, and hydroxylation of estrone, among others. In contrast, the provided reaction involves the oxidation of arachidonate to 8-HETE, which is not one of the substrates or products related to the enzyme's characterized activities. Thus, the gene ENSG00000137869 and the reaction are not related. No
ENSG00000137869 P11511 MAR00933: arachidonate + H+ + NADPH + O2 --> 9-HETE + H2O + NADP+ ENSG00000021461 or ENSG00000100197 or ENSG00000106258 or ENSG00000108242 or ENSG00000130649 or ENSG00000134716 or ENSG00000137869 or ENSG00000138061 or ENSG00000138109 or ENSG00000138115 or ENSG00000140465 or ENSG00000140505 or ENSG00000142973 or ENSG00000155016 or ENSG00000160868 or ENSG00000160870 or ENSG00000165841 or ENSG00000167600 or ENSG00000171903 or ENSG00000186160 or ENSG00000186204 or ENSG00000186377 or ENSG00000186526 or ENSG00000197408 or ENSG00000197446 or ENSG00000197838 or ENSG00000198077 or ENSG00000255974 Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. The gene ENSG00000137869 encodes a cytochrome P450 monooxygenase involved in the conversion of C19 androgens to C18 estrogens, catalyzing successive oxidations of testosterone and androstenedione. However, the reaction provided involves the conversion of arachidonate to 9-HETE using NADPH and O2, which is a different type of reaction not related to the androgen and estrogen conversion catalyzed by the gene product. Therefore, the gene and the reaction are not related. No
ENSG00000137869 P11511 MAR00934: arachidonate + H+ + NADPH + O2 --> 10-HETE + H2O + NADP+ ENSG00000021461 or ENSG00000100197 or ENSG00000106258 or ENSG00000108242 or ENSG00000130649 or ENSG00000134716 or ENSG00000137869 or ENSG00000138061 or ENSG00000138109 or ENSG00000138115 or ENSG00000140465 or ENSG00000140505 or ENSG00000142973 or ENSG00000155016 or ENSG00000160868 or ENSG00000160870 or ENSG00000165841 or ENSG00000167600 or ENSG00000171903 or ENSG00000186160 or ENSG00000186204 or ENSG00000186377 or ENSG00000186526 or ENSG00000197408 or ENSG00000197446 or ENSG00000197838 or ENSG00000198077 or ENSG00000255974 or ENSG00000162365 or ENSG00000187048 Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. The gene ENSG00000137869 encodes a cytochrome P450 monooxygenase which catalyzes the conversion of C19 androgens like androstenedione and testosterone to C18 estrogens such as estrone and estradiol through multiple oxidation steps. In contrast, the provided reaction involves the conversion of arachidonate to 10-HETE using NADPH and O2. This reaction does not align with the known catalytic functions of the cytochrome P450 encoded by ENSG00000137869, which primarily processes steroid hormones, not arachidonic acid. No
ENSG00000162365 Q5TCH4 MAR00934: arachidonate + H+ + NADPH + O2 --> 10-HETE + H2O + NADP+ ENSG00000021461 or ENSG00000100197 or ENSG00000106258 or ENSG00000108242 or ENSG00000130649 or ENSG00000134716 or ENSG00000137869 or ENSG00000138061 or ENSG00000138109 or ENSG00000138115 or ENSG00000140465 or ENSG00000140505 or ENSG00000142973 or ENSG00000155016 or ENSG00000160868 or ENSG00000160870 or ENSG00000165841 or ENSG00000167600 or ENSG00000171903 or ENSG00000186160 or ENSG00000186204 or ENSG00000186377 or ENSG00000186526 or ENSG00000197408 or ENSG00000197446 or ENSG00000197838 or ENSG00000198077 or ENSG00000255974 or ENSG00000162365 or ENSG00000187048 Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000162365 encodes an enzyme that catalyzes the omega- and (omega-1)-hydroxylation of fatty acids like laurate and palmitate but shows no activity towards arachidonic acid. The provided reaction involves the conversion of arachidonate into 10-HETE, which the gene's enzyme does not catalyze according to the given function and catalytic activity annotations. No
ENSG00000137869 P11511 MAR00935: arachidonate + H+ + NADPH + O2 --> 11-HETE + H2O + NADP+ ENSG00000021461 or ENSG00000100197 or ENSG00000106258 or ENSG00000108242 or ENSG00000130649 or ENSG00000134716 or ENSG00000137869 or ENSG00000138061 or ENSG00000138109 or ENSG00000138115 or ENSG00000140465 or ENSG00000140505 or ENSG00000142973 or ENSG00000155016 or ENSG00000160868 or ENSG00000160870 or ENSG00000165841 or ENSG00000167600 or ENSG00000171903 or ENSG00000186160 or ENSG00000186204 or ENSG00000186377 or ENSG00000186526 or ENSG00000197408 or ENSG00000197446 or ENSG00000197838 or ENSG00000198077 or ENSG00000255974 Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. The gene ENSG00000137869 encodes a cytochrome P450 monooxygenase, which catalyzes the conversion of C19 androgens such as androstenedione and testosterone to C18 estrogens like estrone and estradiol. It primarily utilizes molecular oxygen and NADPH in its enzymatic activities and has several specific reactions related to steroid metabolism. The provided reaction involves the conversion of arachidonate to 11-HETE using H+, NADPH, and O2, resulting in H2O and NADP+. This reaction does not involve the substrates or products associated with the cytochrome P450 monooxygenase encoded by ENSG00000137869, nor does it relate to the gene¡¯s described functions in androgen and estrogen metabolism. No
ENSG00000137869 P11511 MAR00936: arachidonate + H+ + NADPH + O2 --> 13-HETE + H2O + NADP+ ENSG00000021461 or ENSG00000100197 or ENSG00000106258 or ENSG00000108242 or ENSG00000130649 or ENSG00000134716 or ENSG00000137869 or ENSG00000138061 or ENSG00000138109 or ENSG00000138115 or ENSG00000140465 or ENSG00000140505 or ENSG00000142973 or ENSG00000155016 or ENSG00000160868 or ENSG00000160870 or ENSG00000165841 or ENSG00000167600 or ENSG00000171903 or ENSG00000186160 or ENSG00000186204 or ENSG00000186377 or ENSG00000186526 or ENSG00000197408 or ENSG00000197446 or ENSG00000197838 or ENSG00000198077 or ENSG00000255974 Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. The gene ENSG00000137869 encodes a cytochrome P450 monooxygenase that catalyzes the conversion of C19 androgens to C18 estrogens through multiple oxidations, utilizing NADPH and oxygen to produce specific steroid derivatives and formic acid (PubMed:27702664, PubMed:2848247). In contrast, the reaction provided involves the conversion of arachidonate to 13-HETE using NADPH and oxygen, which is unrelated to the steroid conversion activities described in the gene's function. Thus, the gene is not involved in the reaction concerning arachidonate conversion. No
ENSG00000137869 P11511 MAR00937: arachidonate + H+ + NADPH + O2 --> 16(R)-HETE + H2O + NADP+ ENSG00000021461 or ENSG00000100197 or ENSG00000106258 or ENSG00000108242 or ENSG00000130649 or ENSG00000134716 or ENSG00000137869 or ENSG00000138061 or ENSG00000138109 or ENSG00000138115 or ENSG00000140465 or ENSG00000140505 or ENSG00000142973 or ENSG00000155016 or ENSG00000160868 or ENSG00000160870 or ENSG00000165841 or ENSG00000167600 or ENSG00000171903 or ENSG00000186160 or ENSG00000186204 or ENSG00000186377 or ENSG00000186526 or ENSG00000197408 or ENSG00000197446 or ENSG00000197838 or ENSG00000198077 or ENSG00000255974 Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000137869 encodes a cytochrome P450 monooxygenase involved primarily in the conversion of C19 androgens to C18 estrogens, and in the metabolism of dihydrotestosterone and estrone. It catalyzes various oxidative reactions involving testosterone, androstenedione, and related substrates using NADPH. However, the given reaction involves the conversion of arachidonate to 16(R)-HETE, a process that is not mentioned in the gene's annotated functions or catalytic activities. Therefore, the gene is not relevant to the specified reaction. No
ENSG00000108242 P33260 MAR00940: arachidonate + H+ + NADPH + O2 --> 19(S)-HETE + H2O + NADP+ ENSG00000021461 or ENSG00000100197 or ENSG00000106258 or ENSG00000108242 or ENSG00000130649 or ENSG00000134716 or ENSG00000137869 or ENSG00000138061 or ENSG00000138109 or ENSG00000138115 or ENSG00000140465 or ENSG00000140505 or ENSG00000142973 or ENSG00000155016 or ENSG00000160868 or ENSG00000160870 or ENSG00000165841 or ENSG00000167600 or ENSG00000171903 or ENSG00000186160 or ENSG00000186204 or ENSG00000186377 or ENSG00000186526 or ENSG00000197408 or ENSG00000197446 or ENSG00000197838 or ENSG00000198077 or ENSG00000255974 Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000108242 encodes a cytochrome P450 monooxygenase involved in retinoid metabolism, specifically hydroxylating all-trans-retinoic acid (atRA). The gene's catalytic activities involve converting atRA to 4-hydroxyretinoate, with the associated reactions supported by molecular oxygen and NADPH via cytochrome P450 reductase. In contrast, the provided reaction involves the conversion of arachidonate to 19(S)-HETE, which is not related to retinoid metabolism. Hence, the gene is not relevant to this arachidonate-related reaction. No
ENSG00000108242 P33260 MAR00943: arachidonate + FADH2 + O2 --> 5,6-EET + FAD + H2O ENSG00000021461 or ENSG00000100197 or ENSG00000106258 or ENSG00000108242 or ENSG00000130649 or ENSG00000134716 or ENSG00000137869 or ENSG00000138061 or ENSG00000138109 or ENSG00000138115 or ENSG00000140465 or ENSG00000140505 or ENSG00000142973 or ENSG00000155016 or ENSG00000160868 or ENSG00000160870 or ENSG00000165841 or ENSG00000167600 or ENSG00000171903 or ENSG00000186160 or ENSG00000186204 or ENSG00000186377 or ENSG00000186526 or ENSG00000197408 or ENSG00000197446 or ENSG00000197838 or ENSG00000198077 or ENSG00000255974 Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000108242 encodes for a cytochrome P450 monooxygenase involved in retinoid metabolism, specifically hydroxylating all-trans-retinoic acid (atRA) to 4-hydroxyretinoate utilizing NADPH and molecular oxygen. The provided reaction involves the conversion of arachidonate to 5,6-EET using FADH2 and O2, which is not related to the retinoid metabolism function of the gene. Thus, the gene and the reaction are not related. No
ENSG00000137869 P11511 MAR00944: arachidonate + FADH2 + O2 --> 5,6-EET + FAD + H2O ENSG00000021461 or ENSG00000100197 or ENSG00000106258 or ENSG00000108242 or ENSG00000130649 or ENSG00000134716 or ENSG00000137869 or ENSG00000138061 or ENSG00000138109 or ENSG00000138115 or ENSG00000140465 or ENSG00000140505 or ENSG00000142973 or ENSG00000155016 or ENSG00000160868 or ENSG00000160870 or ENSG00000165841 or ENSG00000167600 or ENSG00000171903 or ENSG00000186160 or ENSG00000186204 or ENSG00000186377 or ENSG00000186526 or ENSG00000197408 or ENSG00000197446 or ENSG00000197838 or ENSG00000198077 or ENSG00000255974 Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000137869 encodes a cytochrome P450 monooxygenase that catalyzes the conversion of C19 androgens, such as testosterone and androstenedione, into C18 estrogens, such as estrone and estradiol. The gene is involved in multiple oxidative reactions specific to steroid metabolism using molecular oxygen and NADPH. The provided reaction involving arachidonate, FADH2, O2, and the production of 5,6-EET does not involve the substrates (C19 androgens) or the catalytic processes described for cytochrome P450 monooxygenase encoded by this gene. Therefore, the gene is not relevant to the provided reaction. No
ENSG00000108242 P33260 MAR00944: arachidonate + FADH2 + O2 --> 5,6-EET + FAD + H2O ENSG00000021461 or ENSG00000100197 or ENSG00000106258 or ENSG00000108242 or ENSG00000130649 or ENSG00000134716 or ENSG00000137869 or ENSG00000138061 or ENSG00000138109 or ENSG00000138115 or ENSG00000140465 or ENSG00000140505 or ENSG00000142973 or ENSG00000155016 or ENSG00000160868 or ENSG00000160870 or ENSG00000165841 or ENSG00000167600 or ENSG00000171903 or ENSG00000186160 or ENSG00000186204 or ENSG00000186377 or ENSG00000186526 or ENSG00000197408 or ENSG00000197446 or ENSG00000197838 or ENSG00000198077 or ENSG00000255974 Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The provided gene, ENSG00000108242, is involved in retinoid metabolism, specifically hydroxylating all-trans-retinoic acid to 4-hydroxyretinoate using molecular oxygen and NADPH. The gene's function and catalytic activities are linked to reactions involving retinoids, as evidenced by its enzymatic reactions documented in the text. However, the reaction provided (arachidonate + FADH2 + O2 --> 5,6-EET + FAD + H2O) involves the metabolism of arachidonate and does not involve retinoids or NADPH-dependent cytochrome P450 reductase. Thus, there is no direct connection between the gene's function and the provided reaction. No
ENSG00000137869 P11511 MAR00947: arachidonate + FADH2 + O2 --> 8,9-EET + FAD + H2O ENSG00000021461 or ENSG00000100197 or ENSG00000106258 or ENSG00000108242 or ENSG00000130649 or ENSG00000134716 or ENSG00000137869 or ENSG00000138061 or ENSG00000138109 or ENSG00000138115 or ENSG00000140465 or ENSG00000140505 or ENSG00000142973 or ENSG00000155016 or ENSG00000160868 or ENSG00000160870 or ENSG00000165841 or ENSG00000167600 or ENSG00000171903 or ENSG00000186160 or ENSG00000186204 or ENSG00000186377 or ENSG00000186526 or ENSG00000197408 or ENSG00000197446 or ENSG00000197838 or ENSG00000198077 or ENSG00000255974 Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000137869 encodes a cytochrome P450 monooxygenase that catalyzes the conversion of C19 androgens (androstenedione and testosterone) to C18 estrogens (estrone and estradiol) through a series of successive oxidations. This enzyme uses molecular oxygen and NADPH to oxidize its substrates. However, the reaction described (arachidonate + FADH2 + O2 --> 8,9-EET + FAD + H2O) involves the conversion of arachidonate to 8,9-EET, which does not align with the gene's functional activity related to steroid metabolism and specific catalysis pathways described. Therefore, the gene's annotated functions and catalytic activities are not relevant to the provided reaction. No
ENSG00000108242 P33260 MAR00951: arachidonate + FADH2 + O2 --> 11,12-EET + FAD + H2O ENSG00000021461 or ENSG00000100197 or ENSG00000106258 or ENSG00000108242 or ENSG00000130649 or ENSG00000134716 or ENSG00000137869 or ENSG00000138061 or ENSG00000138109 or ENSG00000138115 or ENSG00000140465 or ENSG00000140505 or ENSG00000142973 or ENSG00000155016 or ENSG00000160868 or ENSG00000160870 or ENSG00000165841 or ENSG00000167600 or ENSG00000171903 or ENSG00000186160 or ENSG00000186204 or ENSG00000186377 or ENSG00000186526 or ENSG00000197408 or ENSG00000197446 or ENSG00000197838 or ENSG00000198077 or ENSG00000255974 Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. The gene ENSG00000108242 encodes a cytochrome P450 monooxygenase involved primarily in retinoid metabolism, specifically hydroxylating all-trans-retinoic acid (atRA) to 4-hydroxyretinoate. This reaction uses molecular oxygen and electrons from NADPH via cytochrome P450 reductase. The provided reaction, however, involves the conversion of arachidonate to 11,12-EET using FADH2 and molecular oxygen, which is unrelated to the retinoid metabolism function described for the gene. No
ENSG00000137869 P11511 MAR00954: arachidonate + H+ + NADPH + O2 --> 14,15-EET + H2O + NADP+ ENSG00000021461 or ENSG00000100197 or ENSG00000106258 or ENSG00000108242 or ENSG00000130649 or ENSG00000134716 or ENSG00000137869 or ENSG00000138061 or ENSG00000138109 or ENSG00000138115 or ENSG00000140465 or ENSG00000140505 or ENSG00000142973 or ENSG00000155016 or ENSG00000160868 or ENSG00000160870 or ENSG00000165841 or ENSG00000167600 or ENSG00000171903 or ENSG00000186160 or ENSG00000186204 or ENSG00000186377 or ENSG00000186526 or ENSG00000197408 or ENSG00000197446 or ENSG00000197838 or ENSG00000198077 or ENSG00000255974 Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. The gene ENSG00000137869 encodes a cytochrome P450 monooxygenase involved in the catalytic conversion of C19 androgens such as androst-4-ene-3,17-dione and testosterone to C18 estrogens, including estrone and estradiol. This gene¡¯s function involves multiple oxidative steps that are specific to steroid metabolism, as evidenced by various studies and its different catalytic activities. However, the provided reaction (arachidonate + H+ + NADPH + O2 --> 14,15-EET + H2O + NADP+) is an epoxidation reaction of arachidonic acid resulting in the production of 14,15-EET, which is unrelated to the identified steroid conversion activities of this gene. Therefore, this gene does not participate in the reaction given. No
ENSG00000108242 P33260 MAR00954: arachidonate + H+ + NADPH + O2 --> 14,15-EET + H2O + NADP+ ENSG00000021461 or ENSG00000100197 or ENSG00000106258 or ENSG00000108242 or ENSG00000130649 or ENSG00000134716 or ENSG00000137869 or ENSG00000138061 or ENSG00000138109 or ENSG00000138115 or ENSG00000140465 or ENSG00000140505 or ENSG00000142973 or ENSG00000155016 or ENSG00000160868 or ENSG00000160870 or ENSG00000165841 or ENSG00000167600 or ENSG00000171903 or ENSG00000186160 or ENSG00000186204 or ENSG00000186377 or ENSG00000186526 or ENSG00000197408 or ENSG00000197446 or ENSG00000197838 or ENSG00000198077 or ENSG00000255974 Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. The gene ENSG00000108242 encodes a cytochrome P450 monooxygenase involved in retinoid metabolism, specifically hydroxylating all-trans-retinoic acid (atRA) to 4-hydroxyretinoate. The reactions catalyzed by this enzyme involve all-trans-retinoate and its derivatives, and use molecular oxygen and NADPH. In contrast, the provided reaction involves arachidonate being converted to 14,15-EET with the consumption of NADPH and O2, which is unrelated to retinoid metabolism. Therefore, the gene is not relevant to the provided reaction. No
ENSG00000137869 P11511 MAR00955: arachidonate + FADH2 + O2 --> 14,15-EET + FAD + H2O ENSG00000021461 or ENSG00000100197 or ENSG00000106258 or ENSG00000108242 or ENSG00000130649 or ENSG00000134716 or ENSG00000137869 or ENSG00000138061 or ENSG00000138109 or ENSG00000138115 or ENSG00000140465 or ENSG00000140505 or ENSG00000142973 or ENSG00000155016 or ENSG00000160868 or ENSG00000160870 or ENSG00000165841 or ENSG00000167600 or ENSG00000171903 or ENSG00000186160 or ENSG00000186204 or ENSG00000186377 or ENSG00000186526 or ENSG00000197408 or ENSG00000197446 or ENSG00000197838 or ENSG00000198077 or ENSG00000255974 Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. The gene ENSG00000137869 encodes a cytochrome P450 monooxygenase involved in the conversion of C19 androgens to C18 estrogens through multiple oxidative reactions, utilizing molecular oxygen and NADPH. In contrast, the provided reaction involves the conversion of arachidonate to 14,15-EET with the involvement of FADH2, FAD, and oxygen, which is not associated with the described functions or catalytic activities of the cytochrome P450 monooxygenase encoded by the gene ENSG00000137869. No
ENSG00000137869 P11511 MAR00956: arachidonate + FADH2 + O2 --> 14,15-EET + FAD + H2O ENSG00000021461 or ENSG00000100197 or ENSG00000106258 or ENSG00000108242 or ENSG00000130649 or ENSG00000134716 or ENSG00000137869 or ENSG00000138061 or ENSG00000138109 or ENSG00000138115 or ENSG00000140465 or ENSG00000140505 or ENSG00000142973 or ENSG00000155016 or ENSG00000160868 or ENSG00000160870 or ENSG00000165841 or ENSG00000167600 or ENSG00000171903 or ENSG00000186160 or ENSG00000186204 or ENSG00000186377 or ENSG00000186526 or ENSG00000197408 or ENSG00000197446 or ENSG00000197838 or ENSG00000198077 or ENSG00000255974 Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. The gene ENSG00000137869 encodes a cytochrome P450 monooxygenase involved in the conversion of C19 androgens such as testosterone and androstenedione into C18 estrogens like estrone and estradiol through oxidation reactions. This gene's enzyme also catalyzes several other specific reactions involving androgen substrates and estrone. However, the provided reaction, which involves the conversion of arachidonate to 14,15-EET with FADH2 and O2, is unrelated to the functions and catalytic activities described for the cytochrome P450 monooxygenase encoded by ENSG00000137869. Therefore, this gene does not play a role in the arachidonate metabolism reaction given. No
ENSG00000176153 P18283 MAR01043: 12(S)-HPETE <=> hepoxilin A3 ENSG00000116157 or ENSG00000117592 or ENSG00000164294 or ENSG00000167468 or ENSG00000176153 or ENSG00000198704 or ENSG00000211445 or ENSG00000224586 or ENSG00000233276 Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000176153 catalyzes reactions involving the reduction of various hydroperoxides such as H2O2, cumene hydroperoxide, tert-butyl hydroperoxide, and several fatty acid-derived hydroperoxides in a glutathione-dependent manner. The specific reaction provided, "12(S)-HPETE <=> hepoxilin A3," does not correspond to any of the catalytic activities or substrates mentioned for the gene ENSG00000176153. Therefore, the gene and the reaction are not related. No
ENSG00000224586 O75715 MAR01043: 12(S)-HPETE <=> hepoxilin A3 ENSG00000116157 or ENSG00000117592 or ENSG00000164294 or ENSG00000167468 or ENSG00000176153 or ENSG00000198704 or ENSG00000211445 or ENSG00000224586 or ENSG00000233276 Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000224586 encodes a protein that functions as a glutathione peroxidase, which protects cells from oxidative damage by catalyzing the reduction of hydrogen peroxide and organic hydroperoxides using glutathione. The provided reaction involves the conversion of 12(S)-HPETE to hepoxilin A3, which does not involve glutathione or hydrogen peroxide as substrates or products. Therefore, the gene's function does not relate to this reaction. No
ENSG00000167468 P36969 MAR01045: 12(S)-HPETE <=> hepoxilin A3 ENSG00000116157 or ENSG00000117592 or ENSG00000164294 or ENSG00000167468 or ENSG00000176153 or ENSG00000198704 or ENSG00000211445 or ENSG00000224586 or ENSG00000233276 Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000167468 encodes for an essential antioxidant peroxidase that reduces various hydroperoxides (e.g., phospholipid hydroperoxides, cholesterol hydroperoxide, thymine hydroperoxide) to protect cells from oxidative damage and ferroptosis. It is also involved in reducing fatty acid-derived hydroperoxides and soluble hydroperoxides like H2O2, cumene hydroperoxide, and tert-butyl hydroperoxide. However, the specific reaction provided, "12(S)-HPETE <=> hepoxilin A3," is not a reduction reaction involving glutathione. Instead, it pertains to the conversion of 12(S)-HPETE to hepoxilin A3, which is not within the described catalytic activities of the encoded protein. Therefore, the gene's annotated functions do not relate to the provided reaction. No
ENSG00000211445 P22352 MAR01045: 12(S)-HPETE <=> hepoxilin A3 ENSG00000116157 or ENSG00000117592 or ENSG00000164294 or ENSG00000167468 or ENSG00000176153 or ENSG00000198704 or ENSG00000211445 or ENSG00000224586 or ENSG00000233276 Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000211445 encodes for a protein that catalyzes reactions involving the reduction of hydrogen peroxide, lipid peroxides, and organic hydroperoxides by glutathione. The annotated catalytic activities include reactions that convert 2 glutathione and H2O2 to glutathione disulfide and 2 H2O, and 2 glutathione and tert-butyl hydroperoxide to glutathione disulfide, H2O, and tert-butanol. However, the provided reaction involves the reversible conversion of 12(S)-HPETE to hepoxilin A3, which is not related to the catalytic activities of the gene product in question. Therefore, the gene and the reaction are unrelated. No
ENSG00000211445 P22352 MAR01048: 12(S)-HPETE <=> hepoxilin A3 ENSG00000116157 or ENSG00000117592 or ENSG00000164294 or ENSG00000167468 or ENSG00000176153 or ENSG00000198704 or ENSG00000211445 or ENSG00000224586 or ENSG00000233276 Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000211445 is involved in protecting cells and enzymes from oxidative damage by catalyzing the reduction of hydrogen peroxide, lipid peroxides, and organic hydroperoxides using glutathione as a substrate. However, the reaction provided involves the conversion of 12(S)-HPETE to hepoxilin A3, which does not align with the function of the gene. The gene's catalytic activity does not include this specific reaction, indicating no relevance. No
ENSG00000106258 P20815 MAR00932: arachidonate + H+ + NADPH + O2 --> 8-HETE + H2O + NADP+ ENSG00000021461 or ENSG00000100197 or ENSG00000106258 or ENSG00000108242 or ENSG00000130649 or ENSG00000134716 or ENSG00000137869 or ENSG00000138061 or ENSG00000138109 or ENSG00000138115 or ENSG00000140465 or ENSG00000140505 or ENSG00000142973 or ENSG00000155016 or ENSG00000160868 or ENSG00000160870 or ENSG00000165841 or ENSG00000167600 or ENSG00000171903 or ENSG00000186160 or ENSG00000186204 or ENSG00000186377 or ENSG00000186526 or ENSG00000197408 or ENSG00000197446 or ENSG00000197838 or ENSG00000198077 or ENSG00000255974 Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000106258 encodes a cytochrome P450 monooxygenase that is involved in the metabolism of steroid hormones and vitamins by catalyzing hydroxylation reactions primarily on substrates like 17beta-estradiol, estrone, testosterone, progesterone, androstenedione, and retinoic acid derivatives. Additionally, it metabolizes certain xenobiotics such as nifedipine and cyclosporine. The reaction provided converts arachidonate to 8-HETE using NADPH and O2, but this transformation is not mentioned among the catalytic activities of the gene product. Therefore, the gene does not relate to the described reaction. No
ENSG00000108242 P33260 MAR00932: arachidonate + H+ + NADPH + O2 --> 8-HETE + H2O + NADP+ ENSG00000021461 or ENSG00000100197 or ENSG00000106258 or ENSG00000108242 or ENSG00000130649 or ENSG00000134716 or ENSG00000137869 or ENSG00000138061 or ENSG00000138109 or ENSG00000138115 or ENSG00000140465 or ENSG00000140505 or ENSG00000142973 or ENSG00000155016 or ENSG00000160868 or ENSG00000160870 or ENSG00000165841 or ENSG00000167600 or ENSG00000171903 or ENSG00000186160 or ENSG00000186204 or ENSG00000186377 or ENSG00000186526 or ENSG00000197408 or ENSG00000197446 or ENSG00000197838 or ENSG00000198077 or ENSG00000255974 Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000108242 encodes a cytochrome P450 monooxygenase involved in retinoid metabolism, specifically hydroxylating all-trans-retinoic acid (atRA) to 4-hydroxyretinoate, using molecular oxygen and NADPH. The provided reaction involves the conversion of arachidonate to 8-HETE, which is a different substrate and metabolic pathway. Thus, the gene's function in retinoid metabolism does not relate to the arachidonate conversion reaction. No
feiranl commented 1 month ago

Due to the difficulty in distinguishing enzyme promiscuity in lipid metabolism, I recommend for this issue we only remove ENSG00000162365 from MAR00934, as it is clearly stated that ENSG00000197408 shows no activity towards arachidonic acid and prostaglandin A1. @edkerk what do you think?

edkerk commented 1 month ago

Indeed, these curations involve a lot of Cytochrome P450s with not uncommon wide substrate specificity.

Remove ENSG00000162365 from MAR00934 (see Feiran), and ENSG00000197408 from MAR00932 (involves in epoxidation, making EET, not HETE).

Not suggested by the AI, but ENSG00000186377 should be removed from all reactions in the model, except for MAR00954, MAR00955 and MAR00956.

If anything, for Cytochrome P450s (who can generally be identified by there gene abbreviation starting with CYP), it might be more reasonable to curate per gene: has its protein been assayed for activity --> only keep the gene in that reaction --> remove the gene from all other reactions. But this involves manual curation that is outside the scope of the current approach.