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623d156d00000699 Glycogen catabolic process 1 Mouse

Based on the model details and protein information I've gathered, I'll now conduct a thorough review of GO-CAM model gomodel:623d156d00000699, which is titled "Glycogen catabolic process 1 (Mouse)".

GO-CAM Review: Glycogen catabolic process 1 (Mouse)

Model Overview

  • Model ID: gomodel:623d156d00000699
  • Title: Glycogen catabolic process 1 (Mouse)
  • Taxon: NCBITaxon:10090 (Mouse)
  • Status: Production
  • Comment: This model was sourced from gomodel:R-HSA-70221 and underwent an automated change in 2023-03-16 where RO:0002213 was replaced by RO:0002629

Model Structure and Biological Process

This GO-CAM represents the glycogen catabolic process (GO:0005980) in mouse, showing the enzymatic cascade involved in glycogen breakdown (glycogenolysis). The model includes key enzymes in the pathway:

  1. Phosphorylase kinase (Phkg2) - MGI:MGI:1916211
  2. Glycogen phosphorylase, liver form (Pygl) - MGI:MGI:97829
  3. Amylo-alpha-1,6-glucosidase (Agl) - MGI:MGI:1924809
  4. Phosphoglucomutases (Pgm1 and Pgm2) - MGI:MGI:97565 and MGI:MGI:97564

Model Evaluation

Strengths:

  1. Complete pathway representation: The model captures the major enzymatic activities in glycogen breakdown, from the initial regulatory step (phosphorylase kinase) through glycogen phosphorylase to the final reactions leading to glucose-6-phosphate production.

  2. Proper molecular function annotations: Each protein is annotated with the appropriate molecular function:

  3. Phkg2 with phosphorylase kinase activity (GO:0004689)
  4. Pygl with glycogen phosphorylase activity (GO:0008184)
  5. Agl with amylo-alpha-1,6-glucosidase activity (GO:0004135) and 4-alpha-glucanotransferase activity (GO:0004134)

  6. Pgm1 and Pgm2 with phosphoglucomutase activity (GO:0004614)

  7. Cellular localization: All activities are correctly annotated as occurring in the cytosol (GO:0005829), which is consistent with the known subcellular location of glycogen metabolism.

  8. Evidence support: The model includes appropriate evidence codes and literature citations for the activities and associations.

Areas for Improvement:

  1. Redundant activity representation: There appear to be duplicate activities for Pygl (activities 623d156d00000710 and 623d156d00000705) with identical molecular functions and evidence. This creates unnecessary complexity in the model.

  2. Causal relationship clarity: The model shows Agl activity (amylo-alpha-1,6-glucosidase) providing input for glycogen phosphorylase, which is biochemically incorrect. In glycogen catabolism, glycogen phosphorylase acts first to cleave the α-1,4 glycosidic bonds, while Agl (debranching enzyme) acts on the branch points. These should be parallel activities or glycogen phosphorylase should provide input to Agl.

  3. Missing chemical entities: While the model shows alpha-D-glucose 6-phosphate (CHEBI:58225) as an output of the phosphoglucomutase activities, it doesn't clearly show glycogen as an input to the pathway.

  4. Regulatory relationship representation: The relationship between phosphorylase kinase (Phkg2) and glycogen phosphorylase (Pygl) uses RO:0002629 (directly positively regulates), which is appropriate, but the specific mechanism (phosphorylation of Ser-15 on Pygl) is not represented.

Recommendations for Improvement:

  1. Remove redundant activities: Consolidate the two Pygl activities (623d156d00000710 and 623d156d00000705) into a single representation to simplify the model.

  2. Correct causal relationships: Revise the causal relationship between Agl and Pygl to accurately reflect the biochemical sequence in glycogen catabolism.

  3. Add chemical entities: Include glycogen as an input to the pathway to provide a complete representation of the process.

  4. Expand regulatory information: Consider adding annotations for the phosphorylation of Pygl by Phkg2 to provide additional mechanistic detail.

  5. Add relevant complex information: If any of these enzymes function as complexes (e.g., phosphorylase kinase is a hexadecamer), this could be represented using the complex annotation guidelines.

Conclusion:

Overall, this GO-CAM model provides a good representation of the glycogen catabolic process in mouse. With the suggested improvements, it would more accurately reflect the biological process and be more informative for users. The model aligns with GO-CAM best practices in terms of using appropriate molecular functions, biological processes, and cellular components, but the causal relationships between some enzymes need revision to accurately represent the sequential nature of glycogen breakdown.