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Based on the information I've gathered, I'll now conduct a thorough review of the GO-CAM model for canonical glycolysis (GO:0061621) in Schizosaccharomyces pombe (NCBITaxon:4896).

Review of GO-CAM Model gomodel:663d668500002302

Overview

This model represents canonical glycolysis (GO:0061621) in the fission yeast Schizosaccharomyces pombe. It includes 12 activities that together form a complete glycolytic pathway, with appropriate causal relationships between activities.

Strengths of the Model

  1. Completeness: The model includes all canonical glycolytic enzymes and their respective activities, from hexokinase (beginning of glycolysis) to pyruvate kinase (end of glycolysis).

  2. Appropriate causality: The model correctly uses RO:0002413 ("provides input for") to connect the activities in the pathway in the expected sequential order, representing substrate-product relationships.

  3. Cellular localization: All activities are properly annotated as occurring in the cytosol (GO:0005829), which is the expected cellular location for glycolysis.

  4. Evidence support: Activities are supported by appropriate evidence codes, including direct assays (ECO:0000314), high throughput assays (ECO:0007005), and computational predictions based on sequence similarity (ECO:0000318, ECO:0000250).

  5. Literature references: The model cites relevant literature such as PMID:8549830 (characterizing hexokinases in S. pombe) and PMID:9790887 (pyruvate kinase characterization).

Areas for Improvement

  1. Missing chemical inputs/outputs: While the model does have inputs and outputs for some activities (e.g., hexokinase has D-hexose input, and pyruvate kinase has pyruvate output), most of the intermediate reactions are missing inputs and outputs. Adding these would improve the comprehensiveness of the model.

  2. Redundant causal associations: There are several instances of duplicate causal associations between the same activities. For example:

  3. Activity 663d668500002302/663d668500002432 (triose-phosphate isomerase) has multiple redundant causal connections to the same downstream activities.

  4. Activity 663d668500002302/663d668500002422 (fructose-bisphosphate aldolase) has duplicate causal connections.

  5. Empty evidence fields: Some causal associations have empty evidence fields, which should be populated with appropriate evidence.

  6. Comment indicating incompleteness: The model has a comment stating "To do, add other input chemicals and activities," indicating the curator's awareness that the model remains incomplete.

  7. Branch point representation: Glycolysis has a branch point where dihydroxyacetone phosphate and glyceraldehyde 3-phosphate are produced from fructose 1,6-bisphosphate. The model doesn't clearly represent this branch point and the conversion of dihydroxyacetone phosphate back to the main pathway.

Specific Issues

  1. Activity ID 663d668500002302/663d668500002441 and 663d668500002302/663d668500002589: Both of these represent glyceraldehyde-3-phosphate dehydrogenase (NAD+) (phosphorylating) activity (GO:0004365) enabled by different genes (PomBase:SPBC354.12 and PomBase:SPBC32F12.11). It's unusual to have two separate activities for the same function in a canonical pathway model - this should be reviewed to determine if this represents isozymes and if their inclusion is appropriate.

  2. Activity ID 663d668500002302/663d668500002626 and 663d668500002302/663d668500002636: Similarly, there are two enolase activities (GO:0004634) enabled by different genes (eno101 and eno102), which should be reviewed to determine if both are required in the model.

  3. Inputs and outputs: Key metabolites should be added as inputs and outputs of each reaction:

  4. Glucose, glucose-6-phosphate, fructose-6-phosphate, etc. are missing from most steps.

Recommendations

  1. Complete inputs and outputs: Add all relevant chemical inputs and outputs for each enzymatic step in the pathway.

  2. Remove redundant causal associations: Clean up duplicate causal associations between activities.

  3. Address isozymes: Either justify the inclusion of multiple enzyme isoforms for the same step or simplify to represent the canonical pathway.

  4. Add missing evidence: Ensure all causal associations have appropriate evidence fields.

  5. Represent the branch point: Clearly represent the branch at fructose 1,6-bisphosphate where dihydroxyacetone phosphate and glyceraldehyde 3-phosphate are produced, and the subsequent conversion of dihydroxyacetone phosphate.

Conclusion

This GO-CAM model provides a good representation of the canonical glycolysis pathway in S. pombe, with all key enzymatic activities represented. The activities are properly connected with causal relationships, and most have appropriate evidence and literature support. However, the model could be improved by adding chemical inputs and outputs for all steps, removing redundant causal associations, and addressing the representation of isozymes. Once these issues are addressed, the model will provide a more complete and accurate representation of glycolysis.