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62d0afa500000298 Gluconeogenesis 3 Mouse

Now, let me review this GO-CAM model based on GO-CAM curation best practices. I'll check various aspects of the model including its biological content, connections, and adherence to GO-CAM standards.

Review of GO-CAM Model: gomodel:62d0afa500000298

Basic Information

  • Title: Gluconeogenesis 3 (Mouse)
  • ID: gomodel:62d0afa500000298
  • Taxon: Mouse (NCBITaxon:10090)
  • Status: Production
  • Comments: Sourced from gomodel:R-HSA-70263

Overview

This model represents the gluconeogenesis pathway in mouse. Gluconeogenesis is the metabolic process of generating glucose from non-carbohydrate carbon substrates such as pyruvate, lactate, glycerol, and glucogenic amino acids.

Biological Accuracy Assessment

The model correctly captures the key enzymes involved in gluconeogenesis: - Pyruvate carboxylase (PCX) - Phosphoenolpyruvate carboxykinase (PCK1) - Glucose-6-phosphatase (G6PC1 and G6PC3) - Other enzymes in the pathway: ENO1, PGAM1, PGK1, GAPDH, TPI1, ALDOC, FBP1, GPI1 - Relevant transporters: SLC37A4, SLC25A13, SLC25A12, SLC25A11

The model accurately localizes these enzymes to their appropriate subcellular locations: - Mitochondrial proteins in the mitochondrial matrix or inner membrane - ER-associated proteins like G6PC1 and SLC37A4 in the ER - Cytosolic enzymes in the cytosol

Causal Connectivity Assessment

The model uses the correct causal relationship (RO:0002413 - "provides input for") to connect the enzymatic activities in the gluconeogenesis pathway. The flow of reactions follows the expected pattern of the metabolic pathway:

  1. PCX → GOT2 → (transporters SLC25A13/SLC25A12/SLC25A11) → GOT1
  2. GOT1 → PCK1 → ENO1 → PGAM1 → PGK1 → GAPDH → TPI1/ALDOC → FBP1 → GPI1 → SLC37A4 → G6PC1/G6PC3

This correctly represents the conversion of pyruvate to glucose through the gluconeogenesis pathway.

Evidence Assessment

The model has appropriate evidence for most assertions: - Most activities have evidence codes ECO:0000314 (direct assay evidence) or ECO:0000315 (mutant phenotype evidence) - All assertions include PMID references - Appropriate use of with/from fields for some evidence types

Strengths

  1. Comprehensive representation of the gluconeogenesis pathway
  2. Correct subcellular localization of enzymes
  3. Good use of evidence codes and references
  4. Proper causal connections showing the flow of the pathway
  5. Inclusion of relevant transporters necessary for shuttle mechanisms

Issues/Suggestions for Improvement

  1. Missing Evidence: Some subcellular locations are missing evidence annotations (e.g., for ENO1, PGAM1, FBP1 in cytosol). While these are well-established localizations, they should ideally have evidence and references.

  2. Incomplete "part of" Evidence: Some activities have evidence for molecular function but are missing evidence for the "part_of" relationship to gluconeogenesis (GO:0006094). For example, SLC25A12's participation in gluconeogenesis lacks evidence.

  3. Missing Evidence for Causal Relations: None of the causal relationships (RO:0002413) have evidence annotations. Best practice would be to provide evidence for why one activity provides input for another.

  4. Complex Considerations: The model represents individual gene products rather than the complexes they may form. For example, some enzymes like pyruvate carboxylase can function as multimers. Consider checking if any of these enzymes should be represented as complexes according to GO-CAM complex annotation guidelines.

  5. Redundancy Check: There are two glucose-6-phosphatase activities (G6PC1 and G6PC3) represented. While both are valid, it would be helpful to ensure their distinct roles are clear or if one is more relevant in the specific tissue context.

Recommendations

  1. Add missing evidence annotations for subcellular locations and "part_of" relationships.
  2. Add evidence for causal relationships between activities.
  3. Consider consulting the "How to annotate complexes in GO-CAM" document to check if any of these enzymes should be represented as complexes.
  4. Ensure that all transporter activities have clear evidence for their role in gluconeogenesis.
  5. Review the model for parsimony - ensure there's no redundancy or unnecessary steps that could be simplified.

Overall, this is a well-constructed GO-CAM model that accurately represents the gluconeogenesis pathway in mouse. With the minor improvements suggested, it would fully align with GO-CAM best practices.