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622aace900000790 Galactose catabolic process via UDP galactose

Now I have a good understanding of the model. Let me review the GO-CAM model gomodel:622aace900000790 in detail.

GO-CAM Model Review: gomodel:622aace900000790

Model Title

"Galactose catabolic process via UDP-galactose"

Taxon

NCBITaxon:10090 (Mouse)

Model Status

Production

Model Overview

This model represents the galactose catabolic process via UDP-galactose in mouse (Mus musculus). It was sourced from another model (gomodel:R-HSA-70370) and shows the enzymatic activities involved in this metabolic pathway.

Model Components

The model contains 6 molecular activities connected to form a pathway:

  1. Pgm1 (MGI:MGI:97565) - phosphoglucomutase activity (GO:0004614)
  2. Galk1 (MGI:MGI:95730) - galactokinase activity (GO:0004335)
  3. Galt (MGI:MGI:95638) - UDP-glucose:hexose-1-phosphate uridylyltransferase activity (GO:0008108)
  4. Galm (MGI:MGI:2442420) - aldose 1-epimerase activity (GO:0004034)
  5. Pgm2 (MGI:MGI:97564) - phosphoglucomutase activity (GO:0004614)
  6. Gale (MGI:MGI:1921496) - UDP-glucose 4-epimerase activity (GO:0003978)

Pathway Flow Analysis

The model shows the galactose catabolic pathway with the following flow:

  • Galm catalyzes the conversion of beta-D-galactose (CHEBI:27667) to alpha-D-galactose (CHEBI:28061)
  • Galk1 acts on alpha-D-galactose (input not explicitly shown)
  • Galt acts on the product of Galk1's activity and produces UDP-D-galactose (CHEBI:18307)
  • Gale catalyzes the conversion of UDP-D-galactose (CHEBI:18307) to UDP-D-glucose (CHEBI:18066)
  • Galt can also catalyze the reverse reaction, converting UDP-D-glucose to UDP-D-galactose
  • Pgm1 and Pgm2 both have phosphoglucomutase activity (GO:0004614) that is involved in the pathway

The causal associations in the model use RO:0002413 "provides input for" to connect the activities, which accurately represents the sequential nature of enzymatic reactions in a metabolic pathway.

Evidence Assessment

  • The model uses appropriate evidence codes:
  • ECO:0000314 (direct assay evidence used in manual assertion)
  • ECO:0000315 (mutant phenotype evidence used in manual assertion)
  • ECO:0000266 (sequence orthology evidence used in manual assertion)
  • Evidence is supported by multiple PMIDs, including:
  • PMID:6457600, PMID:31077402 for Pgm1
  • PMID:10915771 for Galk1
  • PMID:8902187 for Galt
  • PMID:30451973 for Galm
  • PMID:28877911 for Gale

The PMID 28877911 I reviewed confirms the role of Gale (UDP-galactose-4-epimerase) in galactose metabolism, specifically in catalyzing the reversible conversion of UDP-galactose to UDP-glucose.

Consistency Check

The model accurately represents the Leloir pathway of galactose metabolism, which is the main pathway for galactose catabolism in mammals. The enzymes and their activities are correctly represented, and the causal relationships reflect the known biochemical pathway.

GO-CAM Best Practices Assessment

  • The model correctly uses molecular activity annotations for each protein.
  • Each activity is properly associated with a biological process (GO:0033499 - galactose catabolic process via UDP-galactose).
  • The model properly specifies input and output chemical entities.
  • Causal associations use the appropriate relation (RO:0002413 - provides input for).
  • No complexes are used in this model, so complex representation guidelines are not applicable.

Issues Identified

  1. Circular Pathway Representation: The model correctly captures the bidirectional nature of the Galt enzyme, which can convert in both directions between UDP-D-galactose and UDP-D-glucose. However, this creates a circular pathway that might be slightly confusing to interpret.

  2. Missing Substrate for Galk1: While the model shows Galk1 has galactokinase activity, the input substrate (alpha-D-galactose) is not explicitly connected to Galk1, although it's shown as the output of Galm.

  3. Duplicate Phosphoglucomutase Activities: Both Pgm1 and Pgm2 are annotated with phosphoglucomutase activity, but their specific roles and the difference between them in the pathway aren't clearly distinguished.

Recommendations

  1. Clarify Bidirectional Flow: Consider annotating the bidirectional nature of the Galt reaction more explicitly, perhaps with a note.

  2. Complete Input Annotations: Ensure all enzymes have their input substrates properly annotated, particularly for Galk1.

  3. Distinguish Duplicate Activities: Provide more context on why both Pgm1 and Pgm2 are included and their specific roles in the pathway, perhaps by adding additional information about their substrate specificity or cellular context.

Conclusion

Overall, this is a well-constructed GO-CAM model that accurately represents the galactose catabolic process via UDP-galactose. The model uses appropriate GO terms, evidence, and relational logic. The connections between activities reflect the known biochemistry of this pathway. The minor issues noted could be addressed to further improve clarity, but they don't significantly impact the biological accuracy or utility of the model.

The model is consistent with the scientific literature and represents a parsimonious visualization of the galactose catabolic pathway that would be recognizable to researchers in the field.