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60ff660000000897 GMP salvage 2b from adenosine Mouse

Based on the information I've gathered, I'll now review the GO-CAM model "GMP salvage 2b, from adenosine (Mouse)" (gomodel:60ff660000000897).

GO-CAM Review: GMP salvage 2b, from adenosine (Mouse)

Model Overview

This model represents the GMP salvage pathway in mouse, starting from adenosine. The pathway shows how adenosine is converted through multiple steps to eventually produce GMP. The model focuses on the activities of several enzymes involved in this purine salvage pathway.

Structure Analysis

The model contains 7 activities connected in a causal pathway:

  1. Adenosine Kinase activity (GO:0004001) - Enabled by Adk (MGI:MGI:87930)
  2. Converts adenosine to AMP

  3. Provides input for three downstream activities (AMP deaminase)

  4. AMP deaminase activity (GO:0003876) - Enabled by three different genes:

  5. Ampd1 (MGI:MGI:88015)
  6. Ampd2 (MGI:MGI:88016)
  7. Ampd3 (MGI:MGI:1096344)

  8. These activities convert AMP to IMP

  9. IMP dehydrogenase activity (GO:0003938) - Enabled by two genes:

  10. Impdh1 (MGI:MGI:96567)
  11. Impdh2 (MGI:MGI:109367)

  12. These convert IMP to XMP

  13. GMP synthase (glutamine-hydrolyzing) activity (GO:0003922) - Enabled by Gmps (MGI:MGI:2448526)

  14. Final step converting XMP to GMP

Evidence Assessment

The model is well-supported by multiple pieces of evidence: - Direct assay evidence (ECO:0000314) - Mutant phenotype evidence (ECO:0000315) - Sequence orthology evidence (ECO:0000266) - Author statements (ECO:0000304)

Each activity is supported by multiple evidence codes with associated PMID references, demonstrating good scientific support for the pathway.

Biological Process Context

The model appropriately places most activities within the "GMP salvage" (GO:0032263) biological process, which is consistent with the pathway being modeled.

Causal Relationships

The causal connections between activities use the appropriate relation "provides input for" (RO:0002413), which correctly represents the substrate-product relationships in an enzymatic pathway. The flow from one enzyme to the next follows the expected metabolic progression in purine salvage.

Strengths of the Model

  1. Comprehensive coverage: The model includes multiple isoforms of enzymes (e.g., AMPD1, AMPD2, AMPD3, and IMPDH1, IMPDH2) that can catalyze the same reaction, accurately representing the biological redundancy.

  2. Well-evidenced: Each activity and relationship is supported by multiple published references.

  3. Clear pathway representation: The model shows a clear linear progression from adenosine to GMP through the expected intermediates.

  4. Appropriate use of GO terms: The molecular functions, biological processes, and relationships are correctly applied.

Suggestions for Improvement

  1. Metabolites not explicitly shown: While the causal connections between enzymatic activities are present, the actual metabolites (adenosine, AMP, IMP, XMP, GMP) are not explicitly represented in the model. Adding the chemical entities would improve clarity.

  2. Cellular compartment information: The model does not specify the cellular locations where these reactions occur. Adding cellular component annotations would enhance the completeness of the model.

  3. Visual organization: The branching of the pathway with multiple AMPD and IMPDH enzymes could be organized more clearly to distinguish parallel pathways vs. alternative isoforms.

Consistency with Literature and GO-CAM Practices

The model is consistent with: - Known purine metabolism pathways as described in literature - GO-CAM best practices for representing enzyme activities and causal relationships - The appropriate use of evidence codes and references

Conclusion

The GO-CAM model "GMP salvage 2b, from adenosine (Mouse)" (gomodel:60ff660000000897) is a well-constructed representation of the GMP salvage pathway. It accurately captures the enzymatic activities, their causal relationships, and provides appropriate evidence for the assertions. The model would benefit from minor enhancements such as explicit representation of metabolites and cellular compartment information, but overall, it is a high-quality GO-CAM that meets the standards for production status.

The model successfully represents the conversion of adenosine to GMP through the sequential activities of adenosine kinase, AMP deaminase, IMP dehydrogenase, and GMP synthase, with appropriate documentation of the alternative enzyme isoforms that can catalyze key steps in the pathway.