Based on my comprehensive review of GO-CAM model 60ff660000001341 titled "AMP salvage 2b, from adenosine (Mouse)", I can provide the following assessment:
Review of GO-CAM Model: AMP salvage 2b, from adenosine (Mouse)¶
Model ID: gomodel:60ff660000001341
Overview¶
This model represents the AMP salvage pathway in mouse, specifically focusing on the conversion of adenosine to AMP. It includes five molecular activities that form a connected pathway through causal relationships using the "provides input for" predicate (RO:0002413).
Strengths of the Model¶
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Appropriate biological pathway representation: The model correctly captures the AMP salvage pathway, which is well-supported by literature evidence, particularly PMID:25681585 which specifically discusses AMP salvage in the context of nucleotide metabolism.
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Well-documented evidence: Each activity in the model is supported by appropriate experimental evidence (ECO:0000314 - direct assay evidence) and specific literature references.
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Proper use of causal relationships: The model uses the "provides input for" (RO:0002413) relationship appropriately to connect molecular functions in the sequence of the pathway.
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Proper gene product assignments: Each molecular function is correctly enabled by the appropriate gene product based on the UniProt entries I reviewed.
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Biological process context: Multiple activities in the model are appropriately placed in the context of the "AMP salvage" (GO:0044209) biological process.
Components Assessment¶
- Adenosine Deaminase (Ada) activity:
- Correctly represented as GO:0004000 (adenosine deaminase activity)
- Appropriately enabled by MGI:MGI:87916 (Ada)
- Evidence from PMID:8064675 and PMID:6771472
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This corresponds to the conversion of adenosine to inosine
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Purine-nucleoside Phosphorylase (Pnp) activity:
- Correctly represented as GO:0004731 (purine-nucleoside phosphorylase activity)
- Appropriately enabled by MGI:MGI:97365 (Pnp)
- Evidence from PMID:8064675 and PMID:6771472
- Correctly placed in AMP salvage biological process
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This corresponds to the conversion of inosine to hypoxanthine
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Hypoxanthine Phosphoribosyltransferase (Hprt1) activity:
- Correctly represented as GO:0004422 (hypoxanthine phosphoribosyltransferase activity)
- Appropriately enabled by MGI:MGI:96217 (Hprt1)
- Evidence from PMID:8064675
- Correctly placed in AMP salvage biological process
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This corresponds to the conversion of hypoxanthine to IMP
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Adenylosuccinate Synthase (Adss1) activity:
- Correctly represented as GO:0004019 (adenylosuccinate synthase activity)
- Appropriately enabled by MGI:MGI:87947 (Adss1)
- Evidence from PMID:1939273 and PMID:11560929
- Correctly placed in AMP salvage biological process
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This corresponds to the conversion of IMP to adenylosuccinate
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Adenylosuccinate Lyase (Adsl) activity:
- Correctly represented as GO:0004018 (N6-(1,2-dicarboxyethyl)AMP AMP-lyase (fumarate-forming) activity)
- Appropriately enabled by MGI:MGI:103202 (Adsl)
- Evidence from PMID:5891253
- This corresponds to the conversion of adenylosuccinate to AMP
Pathway Flow Assessment¶
The model correctly represents the flow of the AMP salvage pathway from adenosine:
- Adenosine → Inosine (by Ada)
- Inosine → Hypoxanthine + Ribose-1-P (by Pnp)
- Hypoxanthine + PRPP → IMP (by Hprt1)
- IMP + Aspartate + GTP → Adenylosuccinate (by Adss1)
- Adenylosuccinate → AMP + Fumarate (by Adsl)
Recommendations for Improvement¶
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Complete biological process context: While three of the five activities are placed in the context of "AMP salvage" biological process, the adenosine deaminase and adenylosuccinate lyase activities could also be tagged with this biological process to provide complete context.
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Consider adding additional evidence: For some of the reactions, additional evidence exists from research papers like PMID:25681585, which specifically discusses this pathway in mouse hearts. This could strengthen the evidentiary basis for the model.
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Consider including regulation information: The model focuses on the enzymatic activities but doesn't capture any regulatory aspects of the pathway. If such information is available from the literature, it could enhance the model.
Conclusion¶
Overall, this is a well-constructed GO-CAM model that accurately represents the AMP salvage pathway in mouse. The model uses appropriate molecular function terms, connects them with correct causal relationships, and provides good evidence for the assertions. The recommended improvements are minor and would only enhance what is already a high-quality model.
The model effectively achieves its goal of representing how adenosine is salvaged to regenerate AMP through a series of enzymatic reactions in mouse cells, which is important for maintaining the adenine nucleotide pool during conditions of metabolic stress.