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60ff660000000882 GMP salvage 2a from adenosine Mouse

Based on my review of the model and the GO-CAM documentation, here's my assessment of GO-CAM model 60ff660000000882 "GMP salvage 2a, from adenosine (Mouse)":

GO-CAM Review for Model gomodel:60ff660000000882

Model Overview

This model represents the GMP salvage pathway in mouse (taxon NCBITaxon:10090), showing how adenosine is converted to GMP through a series of enzymatic reactions. The model was sourced from Reactome pathways R-HSA-73817 and R-HSA-74217.

Molecular Activities and Causal Flow

The model includes the following activities: 1. Ada (MGI:MGI:87916) - adenosine deaminase activity (GO:0004000) 2. Pnp (MGI:MGI:97365) - purine-nucleoside phosphorylase activity (GO:0004731) 3. Hprt1 (MGI:MGI:96217) - hypoxanthine phosphoribosyltransferase activity (GO:0004422) 4. Impdh1 (MGI:MGI:96567) - IMP dehydrogenase activity (GO:0003938) 5. Impdh2 (MGI:MGI:109367) - IMP dehydrogenase activity (GO:0003938) 6. Gmps (MGI:MGI:2448526) - GMP synthase (glutamine-hydrolyzing) activity (GO:0003922)

The causal flow is represented using RO:0002413 (provides input for) relations, following a logical pathway from adenosine → hypoxanthine → IMP → XMP → GMP.

Evidence Assessment

The model is well supported by experimental evidence: - Most activities have direct assay evidence (ECO:0000314) or mutant phenotype evidence (ECO:0000315) - Key publications such as PMID:718989 support the connections between activities - The evidence aligns with the literature about purine metabolism, including the biochemical study I examined (PMID:718989) which shows details of purine metabolism and nucleotide pools in neuroblastoma cells

Quality Control Assessment

Strengths:

  1. Pathway Integrity: The model correctly represents the sequence of biochemical reactions in the GMP salvage pathway
  2. Evidence Quality: Uses appropriate evidence codes with specific PMIDs for each activity
  3. Biological Accuracy: The enzymatic activities align with known functions of these proteins
  4. Completeness: All essential enzymes for this pathway are included
  5. Alternative Pathways: Correctly represents that both Impdh1 and Impdh2 can catalyze the same reaction step (IMP → XMP)

Areas for Improvement:

  1. Biological Process Annotation: While most activities have part_of relations to GO:0032263 (GMP salvage), Ada (adenosine deaminase) is missing this annotation
  2. Missing Evidence: The causal association between Ada and Pnp has no evidence associated with it
  3. Cellular Component: No cellular component annotations are provided, which would add contextual information
  4. Additional Context: The model could benefit from information about regulation, especially since the literature indicates this pathway is subject to regulatory processes

Compliance with GO-CAM Best Practices

The model follows GO-CAM guidelines for representing metabolic pathways: - Uses appropriate causal relations (RO:0002413 - provides input for) - Represents each functional entity with its molecular function - Correctly links activities to specific gene products

Suggestions for Improvement

  1. Add the "part of" relation to link Ada (adenosine deaminase) activity to GO:0032263 (GMP salvage)
  2. Add evidence to support the causal relationship between Ada and Pnp
  3. Include cellular component annotations for each activity
  4. Consider adding regulatory elements if supported by evidence, as purine metabolism is known to be highly regulated

Conclusion

This is a well-constructed model of the GMP salvage pathway in mouse with accurate representation of the enzymatic activities and their causal connections. The minor improvements suggested above would enhance the model's completeness and adherence to GO-CAM best practices but don't affect the overall validity of the biological content.

The model is consistent with experimental evidence and textbook knowledge of purine metabolism, as confirmed by the literature review. The activities are correctly connected in a way that represents the actual flow of the GMP salvage pathway from adenosine.