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Based on my review of the model and relevant information, I'll now provide a detailed review of GO-CAM model 65f3ae5c00002208 titled "Positive regulation of glycogen catabolic process 1 (Mouse)".

GO-CAM Model Review: gomodel:65f3ae5c00002208

Overview

Title: Positive regulation of glycogen catabolic process 1 (Mouse)
ID: gomodel:65f3ae5c00002208
Taxon: Mouse (NCBITaxon:10090)
Status: Production

Model Description

This GO-CAM depicts the glycogen catabolic process in mouse, focusing on enzymes involved in glycogen degradation. The model includes activities of multiple enzymes in the glycogen breakdown pathway, with connections showing the flow of biological activities.

Key Components of the Model

  1. Main Enzymes in the Model:
  2. Glycogen phosphorylase (MGI:MGI:97829, Pygl)
  3. Glycogen debranching enzyme (MGI:MGI:1924809, Agl) with dual activities:
    • 4-alpha-glucanotransferase activity (GO:0004134)
    • Amylo-alpha-1,6-glucosidase activity (GO:0004135)
  4. Phosphorylase kinase (MGI:MGI:1916211, Phkg2)

  5. Phosphoglucomutase 1 and 2 (MGI:MGI:97565 and MGI:MGI:97564)

  6. Biological Process:

  7. All activities are part of glycogen catabolic process (GO:0005980)

  8. Cellular Location:

  9. Activities occur in the cytosol (GO:0005829)

  10. Molecular Outputs:

  11. Alpha-D-glucose (CHEBI:17925)
  12. Alpha-D-glucose 6-phosphate(2-) (CHEBI:58225)

Causal Connections

The model shows a regulatory pathway through the following causal relationships:

  1. Phosphorylase kinase (MGI:MGI:1916211) directly positively regulates (RO:0002629) glycogen phosphorylase activity

  2. Glycogen phosphorylase (MGI:MGI:97829) provides input for (RO:0002413) multiple downstream activities:

  3. Glycogen debranching enzyme (4-alpha-glucanotransferase activity)

  4. Both phosphoglucomutase activities

  5. The 4-alpha-glucanotransferase activity of glycogen debranching enzyme provides input for (RO:0002413) its own amylo-alpha-1,6-glucosidase activity

  6. The amylo-alpha-1,6-glucosidase activity provides input for (RO:0002413) glycogen phosphorylase activity (second instance)

Evidence

The model contains appropriate evidential support: - Experimental evidence codes (ECO:0000314, ECO:0000315) from relevant literature - Multiple PMIDs are cited, including PMID:24613482 which details a mouse model of glycogen storage disease type III - Appropriate use of evidence codes for the different assertions

Strengths of the Model

  1. Biochemical Accuracy: The model accurately represents the sequence of enzymatic activities in glycogen breakdown, consistent with the literature.

  2. Appropriate Evidence: Each activity is supported by experimental evidence from literature, properly annotated with ECO terms.

  3. Comprehensive Pathway Representation: The model includes the key enzymes in the glycogen catabolic process, showing both debranching and phosphorylase-dependent degradation.

  4. Cellular Context: The model correctly places these activities in the cytosol.

  5. Causality Representation: The causal flow between activities is logical and represents the biological sequence of events.

Suggestions for Improvement

  1. Complete Regulatory Context: The model shows phosphorylase kinase positively regulating glycogen phosphorylase, but the upstream activators of phosphorylase kinase (such as calcium or protein kinase A) are not included. Adding these would provide a more complete regulatory context.

  2. Metabolic Outputs: While the model shows glucose and glucose-6-phosphate as outputs, it might benefit from showing the fate of these products (e.g., entry into glycolysis).

  3. Feedback Regulation: The model doesn't include feedback regulation mechanisms that control glycogen breakdown. Including these would enhance the biological completeness.

  4. Alternative Debranching Pathway: The model appropriately shows the dual activities of the glycogen debranching enzyme (Agl), but could clarify that these are two activities of the same protein rather than separate instances.

Conclusion

This GO-CAM model (gomodel:65f3ae5c00002208) provides a well-structured and evidentially supported representation of the glycogen catabolic process in mice. The model correctly represents the causal flow between the different enzymatic activities and includes appropriate molecular functions, cellular components, and biological processes.

The relevance of this model is particularly high given the connection to glycogen storage disease type III (as evidenced by PMID:24613482), where mutations in the glycogen debranching enzyme (Agl) lead to disease. The model follows GO-CAM best practices for representation of molecular activities and their causal connections.

Overall, this is a high-quality model that could serve as a useful reference for understanding glycogen catabolism and the molecular basis of related metabolic disorders.