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Based on my review of the GO-CAM model "gomodel:635b1e3e00000382" (Xylulose-5-Phosphate biosynthetic process 1 (Mouse)), I will provide a comprehensive assessment focusing on its biological accuracy, adherence to GO-CAM guidelines, and overall quality.

GO-CAM Model Review: Xylulose-5-Phosphate biosynthetic process 1 (Mouse)

Model Overview

This GO-CAM model (gomodel:635b1e3e00000382) describes the xylulose 5-phosphate biosynthetic process in mouse, focusing on the interactions between four key enzymes involved in glycolysis and the pentose phosphate pathway:

  1. Transketolase (TKT) - MGI:MGI:105992 (UniProt: P40142)
  2. Transaldolase (TALDO1) - MGI:MGI:1274789 (UniProt: Q93092)
  3. Triose-phosphate isomerase (TPI1) - MGI:MGI:98797 (UniProt: P17751)
  4. Glucose-6-phosphate isomerase (GPI1) - MGI:MGI:95797 (UniProt: P06745)

Biological Content Assessment

Pathway Accuracy

The model accurately represents the enzymatic activities involved in the xylulose 5-phosphate biosynthetic pathway:

  1. Transketolase (TKT) catalyzes the transfer of two-carbon units (ketol group) from a ketose donor to an aldose acceptor. In this pathway, it's correctly shown converting glyceraldehyde 3-phosphate and sedoheptulose 7-phosphate to D-xylulose 5-phosphate and ribose 5-phosphate.

  2. Transaldolase (TALDO1) is correctly represented as catalyzing the reversible conversion of sedoheptulose 7-phosphate and D-glyceraldehyde 3-phosphate to erythrose 4-phosphate and fructose 6-phosphate.

  3. Triose-phosphate isomerase (TPI1) is appropriately shown converting glycerone phosphate (dihydroxyacetone phosphate) to D-glyceraldehyde 3-phosphate.

  4. Glucose-6-phosphate isomerase (GPI1) is correctly shown producing fructose 6-phosphate, which feeds into this pathway.

Causal Connections

The model uses the correct causal relation "RO:0002413" (provides input for) to connect the activities of these enzymes, showing how the product of one enzyme activity becomes the substrate for another:

  • TPI1 → TKT (glyceraldehyde 3-phosphate as output of TPI1 is input for TKT)
  • TPI1 → TALDO1 (glyceraldehyde 3-phosphate as output of TPI1 is input for TALDO1)
  • GPI1 → TKT (outputs of GPI1 feed into subsequent reactions)
  • TKT → TALDO1 (bidirectional relationship showing how these activities are interconnected)
  • TALDO1 → TKT (bidirectional relationship showing how these activities are interconnected)

Evidence Support

The model uses appropriate evidence codes:

  • ECO:0000314 (direct assay evidence used in manual assertion) - Used for most connections
  • ECO:0000315 (mutant phenotype evidence used in manual assertion) - Used for GPI1
  • ECO:0000304 (author statement supported by traceable reference) - Used for biological process associations
  • ECO:0000316 (genetic interaction evidence used in manual assertion) - Used for TPI1

The literature cited (PMIDs 5360673, 27103217, 3443296, 30174313) is relevant to the pathway, although I couldn't fully retrieve the earliest reference (5360673).

GO-CAM Best Practices Assessment

Molecular Function Representation

The model correctly follows GO-CAM best practices for molecular function representation:

  1. Each enzyme is represented with its specific molecular function:
  2. Transketolase activity (GO:0004802)
  3. Transaldolase activity (GO:0004801)
  4. Triose-phosphate isomerase activity (GO:0004807)

  5. Glucose-6-phosphate isomerase activity (GO:0004347)

  6. All activities have appropriate enabled_by associations to the correct gene products.

Cellular Component Representation

The model appropriately represents the cellular location of activities: - All activities occur in the cytosol (GO:0005829), which is correct for these glycolytic/pentose phosphate pathway enzymes.

Biological Process Association

The model correctly associates the activities with appropriate biological processes: - Transketolase and transaldolase activities are part of the xylulose 5-phosphate biosynthetic process (GO:1901159) - Triose-phosphate isomerase and glucose-6-phosphate isomerase activities are part of canonical glycolysis (GO:0061621)

This accurately represents the biological reality that these enzymes participate in interconnected metabolic networks.

Substrate/Product Representation

The model accurately represents the molecular inputs and outputs for each enzymatic reaction: - Transketolase: - Inputs: D-glyceraldehyde 3-phosphate (CHEBI:59776), sedoheptulose 7-phosphate (CHEBI:15721) - Outputs: D-xylulose 5-phosphate (CHEBI:57737), D-erythrose 4-phosphate (CHEBI:16897)

  • Transaldolase:
  • Inputs: D-erythrose 4-phosphate (CHEBI:16897), fructose 6-phosphate (CHEBI:57634)

  • Outputs: D-glyceraldehyde 3-phosphate (CHEBI:59776), sedoheptulose 7-phosphate (CHEBI:15721)

  • Triose-phosphate isomerase:

  • Inputs: Glycerone phosphate (CHEBI:57642)

  • Outputs: D-glyceraldehyde 3-phosphate (CHEBI:59776)

  • Glucose-6-phosphate isomerase:

  • Outputs: Fructose 6-phosphate (CHEBI:57634)

Causal Flow and Readability

The model presents a clear causal flow showing how these enzymes work together in the pathway. The connections between activities logically follow the flow of metabolites through the pathway, which enhances readability and comprehension.

Recommendations for Improvement

While the model is overall very good, I have a few minor suggestions for improvement:

  1. Add Input for GPI1: The model doesn't specify the input for glucose-6-phosphate isomerase, which should be glucose 6-phosphate (CHEBI:58225). Adding this would make the reaction complete.

  2. Clarify Bidirectional Reactions: Some of these reactions are reversible in vivo. The use of RO:0002413 (provides input for) in both directions between TKT and TALDO1 implies this, but it might be clearer to explicitly note the reversibility of these reactions in annotations.

  3. Add More Contextual Information: Adding annotations about conditions that affect the directionality of these reactions (such as substrate availability or energy status of the cell) would enhance the biological context.

  4. Consider Adding Regulatory Components: If known, adding how these enzymes are regulated (e.g., by allosteric modulators or post-translational modifications) would provide a more comprehensive picture of the pathway.

Conclusion

This GO-CAM model (gomodel:635b1e3e00000382) is a high-quality representation of the xylulose 5-phosphate biosynthetic pathway in mouse. It follows GO-CAM best practices, is biologically accurate, and is supported by appropriate evidence. The model correctly represents the enzymatic activities, their subcellular locations, and their relationships in the pathway. With the suggested minor improvements, it would provide an even more comprehensive representation of this important metabolic pathway.