Skip to content

Based on all the information gathered, let me now provide a detailed review of the GO-CAM model (gomodel:60ff660000000917):

GO-CAM Model Review: GMP Salvage 3, from Adenine (Mouse)

Model Summary

  • ID: gomodel:60ff660000000917
  • Title: GMP salvage 3, from adenine (Mouse)
  • Taxon: Mouse (NCBITaxon:10090)
  • Status: Production
  • Comments: Sourced from: R-HSA-73817 and R-HSA-74217 (Reactome pathways)

Overall Assessment

This GO-CAM model represents the GMP salvage pathway in mouse, specifically focusing on the conversion of adenine to GMP. The model captures the key enzymatic activities involved in this process with appropriate causal relationships.

Biological Content Review

The model accurately represents the GMP salvage pathway, which is an important pathway for recycling purine bases to maintain nucleotide pools without the high energy cost of de novo synthesis. The model shows:

  1. The initial step with adenine phosphoribosyltransferase (APRT) converting adenine to AMP
  2. Multiple routes of AMP deamination by three different AMP deaminases (AMPD1, AMPD2, AMPD3) to form IMP
  3. Conversion of IMP to XMP by two IMP dehydrogenases (IMPDH1, IMPDH2)
  4. Final conversion of XMP to GMP by GMP synthase (GMPS)

This pathway is consistent with established biochemical knowledge about purine nucleotide metabolism and the GMP salvage pathway.

Technical Compliance Assessment

1. Activity Flow and Causal Relationships

The model uses the "provides input for" (RO:0002413) relationship consistently to connect activities in the pathway: - APRT provides input for multiple AMPD enzymes - AMPD enzymes provide input for IMPDH enzymes - IMPDH enzymes provide input for GMP synthase

This is correct for a metabolic pathway, where each enzyme converts a substrate to a product that serves as the substrate for the next enzyme.

2. Gene Product Annotations

Each activity is properly enabled by a specific gene product: - MGI:MGI:88061 (Aprt) - Adenine phosphoribosyltransferase activity - MGI:MGI:88015 (Ampd1) - AMP deaminase activity - MGI:MGI:88016 (Ampd2) - AMP deaminase activity - MGI:MGI:1096344 (Ampd3) - AMP deaminase activity - MGI:MGI:96567 (Impdh1) - IMP dehydrogenase activity - MGI:MGI:109367 (Impdh2) - IMP dehydrogenase activity - MGI:MGI:2448526 (Gmps) - GMP synthase activity

3. Biological Process Context

All relevant activities are correctly placed within the biological process context of "GMP salvage" (GO:0032263).

4. Evidence Quality

The model uses appropriate evidence codes for the annotations: - ECO:0000314 (direct assay evidence used in manual assertion) - ECO:0000315 (mutant phenotype evidence used in manual assertion) - ECO:0000304 (author statement supported by traceable reference used in manual assertion)

Each activity is supported by at least one literature reference (PMID).

5. Complex Representation

The model does not appear to include protein complexes. According to the UniProt information for IMPDH2, this enzyme can form homotetramers, but since the molecular function is directly associated with the gene product rather than a complex, this representation is appropriate according to the GO-CAM guidelines for annotating complexes (the subunit that carries the activity is known).

Areas for Improvement

  1. Missing Process Annotations: Some activities don't have explicit "part_of" process annotations, which would be beneficial for completeness.

  2. Evidence for Causal Relationships: Some causal associations lack evidence annotations. Adding evidence to support all causal claims would strengthen the model.

  3. Complete Pathway Context: While the model focuses on the GMP salvage pathway, it could benefit from placing this pathway in the broader context of purine metabolism by connecting it to related pathways.

Literature Consistency

The model is consistent with current understanding of the GMP salvage pathway as described in the literature. The key enzymes, their activities, and the pathway flow are accurately represented.

Conclusion

The GO-CAM model (gomodel:60ff660000000917) represents a biologically accurate and technically sound representation of the GMP salvage pathway from adenine in mouse. The model follows GO-CAM best practices for the most part, with only minor improvements suggested. The causal relationships between activities are appropriate, and the model is supported by published literature. This model is suitable for production use and provides a valuable resource for understanding GMP salvage metabolism.