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Finally, let me put together a detailed review of the GO-CAM model based on all the information I've gathered.

GO-CAM Model Review: gomodel:5fa76ad400000374

Model Overview

This GO-CAM model (gomodel:5fa76ad400000374) describes the "IMP catabolic process to allantoin (Mouse)" pathway. The model represents the enzymatic pathway for the degradation of purines, specifically the conversion of IMP to allantoin in mouse.

Pathway Context

The pathway depicted is the purine catabolism pathway that converts IMP (inosine monophosphate) through a series of enzymatic steps to finally produce allantoin. This is an important metabolic pathway in many organisms, though humans and other primates have lost the ability to degrade uric acid to allantoin due to the loss of functional urate oxidase.

Model Structure and Components

Core Enzymes and Activities

The model includes several key enzymes:

  1. NT5C, NT5C1A, NT5C2 (IMP 5'-nucleotidase activity) - Convert IMP to inosine
  2. PNP (Purine-nucleoside phosphorylase) - Converts inosine to hypoxanthine
  3. XDH (Xanthine dehydrogenase/oxidase) with multiple activities:
  4. Hypoxanthine dehydrogenase activity
  5. Hypoxanthine oxidase activity
  6. Xanthine dehydrogenase activity
  7. Xanthine oxidase activity
  8. UOX (Urate oxidase) - Converts urate to 5-hydroxyisourate
  9. URAH (HIU hydrolase) - Converts 5-hydroxyisourate to OHCU
  10. URAD (OHCU decarboxylase) - Converts OHCU to allantoin

Cellular Localization

The model appropriately indicates different cellular localizations for different activities: - Cytosol (GO:0005829) for early steps involving NT5C enzymes, PNP, and some XDH activities - Peroxisome (GO:0005777) for later steps involving UOX, URAH, and URAD

Causal Connections

The model uses the RO:0002413 provides input for relation throughout the pathway to show the flow of enzymatic activities. This is appropriate for metabolic pathways where the product of one reaction becomes the substrate for the next.

Evidence Quality

The model is well-supported by experimental evidence, primarily with: - ECO:0000314 (direct assay evidence used in manual assertion) - ECO:0000266 (sequence orthology evidence used in manual assertion) - ECO:0000315 (mutant phenotype evidence used in manual assertion)

Key publications cited include PMID:8064675, PMID:16462750, and several others that support the enzymatic activities and pathway organization.

Strengths of the Model

  1. Comprehensive pathway representation: The model captures the complete pathway from IMP to allantoin, including all intermediate steps.

  2. Proper cellular localization: The model correctly represents the differential localization of activities between cytosol and peroxisome, which is biologically accurate.

  3. Multiple activities of XDH: The model correctly represents the multiple activities of xanthine dehydrogenase/oxidase, which can function both as a dehydrogenase and an oxidase with different substrates.

  4. Well-evidenced: Most assertions in the model are supported by appropriate experimental evidence.

  5. Includes recently discovered enzymes: The model includes URAH and URAD, which as shown in PMID:16462750, were relatively recently discovered to complete the pathway from uric acid to allantoin.

Areas for Improvement

  1. Missing cellular localization for some activities: The assertion for PNP (gomodel:5fa76ad400000374/5fa76ad400000376) has an empty evidence field for its cellular localization in the cytosol. This should be completed with appropriate evidence.

  2. Causal association evidence: Some causal associations lack evidence (e.g., between NT5C1A activity and PNP activity). All causal connections should have evidence supporting the pathway flow.

  3. Metabolic intermediates: The model only explicitly shows allantoin as an output, but could be enhanced by representing the other metabolic intermediates (hypoxanthine, xanthine, urate, 5-hydroxyisourate, OHCU) as has_output and has_input relations to better document the pathway.

Biological Accuracy

Based on the literature review and UniProt information for key proteins, this model accurately represents the IMP to allantoin catabolic pathway in mouse. The inclusion of the recently discovered enzymes URAH and URAD (from PMID:16462750) shows that the model is up-to-date with current knowledge.

The placement of these enzymes in peroxisomes is correct, as they contain peroxisomal targeting signals as noted in the Ramazzina et al. paper (PMID:16462750).

Conclusion

This GO-CAM model (gomodel:5fa76ad400000374) is a high-quality representation of the IMP catabolic pathway to allantoin in mouse. It includes all key enzymatic steps, appropriate cellular localization, and is well-supported by evidence. The minor issues noted should be addressed to further improve the model, but they do not significantly impact the overall quality or accuracy of the pathway representation.