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66b5638000000056 GDP L fucose salvage Mouse

Based on my review of the GO-CAM model for "GDP-L-fucose salvage (Mouse)" (gomodel:66b5638000000056), I'll provide a comprehensive QC assessment:

GO-CAM Review: GDP-L-fucose Salvage Pathway (Mouse)

Model ID: gomodel:66b5638000000056

Overall Assessment

This GO-CAM model represents the GDP-L-fucose salvage pathway in mouse, showing how free fucose is taken up, phosphorylated, and converted to GDP-L-fucose for use in glycosylation. The model captures the key enzymes and transport steps in this pathway.

Biological Content Accuracy

The model accurately represents the GDP-L-fucose salvage pathway as described in the literature, particularly in reference PMID:14686921, which describes the cloning and expression of murine L-fucokinase and GDP-L-fucose pyrophosphorylase. The specific sequence is well-supported:

  1. Fucose transport: SLC2A1 (GLUT1) transports L-fucose across the plasma membrane (based on PMID:36423686)
  2. Fucokinase activity: FCSK phosphorylates L-fucose to L-fucose-1-phosphate
  3. GDP-L-fucose pyrophosphorylase activity: FPGT converts L-fucose-1-phosphate to GDP-L-fucose
  4. GDP-L-fucose transport: SLC35C1 transports GDP-L-fucose to the Golgi apparatus

The model also correctly includes FUOM (fucose mutarotase), which catalyzes the conversion of α-L-fucose to β-L-fucose, providing substrate for FCSK.

Compliance with GO-CAM Best Practices

The model generally follows GO-CAM best practices:

  1. Proper causal connections: The model uses RO:0002413 ("provides input for") appropriately to connect the activities in the pathway.
  2. Proper cellular component annotation: Each activity is annotated with the correct cellular component (cytosol, Golgi membrane, plasma membrane).
  3. Evidence codes: Appropriate evidence codes are used, including ECO:0000314 (direct assay) and ECO:0000315 (mutant phenotype).
  4. Input/output annotations: The chemical inputs and outputs are properly annotated for each reaction.

Suggestions for Improvement

While the model is generally well-constructed, I identified a few areas for improvement:

  1. Missing evidence for some inputs/outputs: Some of the molecular associations (for input/output molecules) lack evidence annotations. For example, in the FCSK activity (gomodel:66b5638000000056/66b5638000000080), inputs CHEBI:42589 and CHEBI:30616 have no evidence annotations.

  2. Missing cellular component annotation: The FPGT activity (gomodel:66b5638000000056/66b5638000000078) has a cellular component (GO:0005829 - cytosol) but lacks evidence annotation for this assertion.

  3. Suggestion for improved pathway flow: The model could be enhanced by explicitly connecting the initial transport activity (SLC2A1) to subsequent enzymes. Currently, SLC2A1 (GLUT1) is shown positively regulating FCSK, which is correct, but a clearer representation of how extracellular fucose enters the metabolic pathway might be beneficial.

  4. Complete the cycle: The model could potentially be expanded to show what happens to GDP-L-fucose after it's transported into the Golgi - i.e., its incorporation into glycoproteins and glycolipids.

Literature Support

The biological content of the model is well-supported by multiple publications:

  • PMID:14686921 establishes the key enzymes of the salvage pathway
  • PMID:36423686 documents SLC2A1 (GLUT1) as an L-fucose transporter
  • PMID:17602138 and PMID:19524593 support the role of FUOM in the pathway
  • PMID:17276979 supports the SLC35C1 GDP-fucose transporter function

Conclusion

This GO-CAM model accurately represents the GDP-L-fucose salvage pathway in mouse. It captures the key molecular activities, their correct sequence, and appropriate cellular locations. With minor improvements to evidence annotations and component locations, this would be an exemplary GO-CAM model for a metabolic pathway.

The model successfully captures the conversion of extracellular L-fucose to intracellular GDP-L-fucose for use in glycosylation, with each step represented by the appropriate enzyme and molecular function.