5fadbcf000000942 dTMP catabolic process Mouse

Based on a thorough review of the GO-CAM model "gomodel:5fadbcf000000942" titled "dTMP catabolic process (Mouse)", I will provide a structured analysis of its biological content, structural organization, and adherence to GO-CAM best practices.

Model Overview¶

This model represents the dTMP (deoxythymidine monophosphate) catabolic pathway in mouse, showing the sequential enzymatic steps involved in the degradation of pyrimidine nucleotides. The model includes 7 distinct molecular activities connected through causal relationships.

Biological Content Analysis¶

Pathway Representation¶

The model correctly depicts the pyrimidine degradation pathway, particularly focused on the catabolism of dTMP. The enzymes involved are appropriately connected in sequential order representing the flow of biochemical reactions:

5'-nucleotidases (NT5C and NT5C3) convert dTMP to thymidine by removing the phosphate group
Thymidine phosphorylases (TYMP and UPP1) convert thymidine to thymine and 2-deoxyribose-1-phosphate
Dihydropyrimidine dehydrogenase (DPYD) reduces thymine to dihydrothymine
Dihydropyrimidinase (DPYS) catalyzes the hydrolytic ring opening of dihydrothymine to N-carbamyl-β-aminoisobutyric acid
β-ureidopropionase (UPB1) completes the pathway by converting N-carbamyl-β-aminoisobutyric acid to β-aminoisobutyric acid, ammonia and CO2

Evidence Support¶

The model is well-supported by evidence from the literature: - PMID:8083224 supports DPYD (dihydropyrimidine dehydrogenase) function - PMID:22525402 supports UPB1 (β-ureidopropionase) function - PMID:12077348 supports TYMP (thymidine phosphorylase) activity - PMID:6301357 supports NT5C (5'-nucleotidase) function

Subcellular Localization¶

The model includes cellular component annotations: - Most enzymes are properly localized to the cytosol (GO:0005829) - AGXT2 is appropriately localized to the mitochondrion (GO:0005739)

Biological Process Context¶

All activities are appropriately part of dTMP catabolic process (GO:0046074), which provides a clear biological context for the model.

Structural Organization Analysis¶

Causal Connections¶

The model uses causal relationships correctly with the predicate "RO:0002413" (provides input for) connecting sequential enzymatic activities, reflecting the flow of metabolites through the pathway. This correctly shows how the product of one enzyme becomes the substrate for the next enzyme.

Activity Representation¶

Each activity has: - A molecular function term (e.g., GO:0004157 for dihydropyrimidinase activity) - An enabled_by relationship to the gene product performing the activity (e.g., MGI:MGI:1928679 for Dpys) - In most cases, a subcellular location (occurs_in) - A biological process context (part_of)

Causal Flow¶

The activities flow as follows: 1. NT5C (5'-nucleotidase) → TYMP/UPP1 (thymidine phosphorylases) 2. TYMP/UPP1 → DPYD (dihydropyrimidine dehydrogenase) 3. DPYD → DPYS (dihydropyrimidinase) 4. DPYS → UPB1 (β-ureidopropionase)

This accurately reflects the actual flow of metabolites in the pyrimidine degradation pathway.

GO-CAM Best Practices Compliance¶

Use of Evidence Codes¶

The model uses appropriate evidence codes: - ECO:0000266 (sequence orthology evidence) for orthology-based annotations - ECO:0000314 (direct assay evidence) for experimentally confirmed activities - ECO:0000315 (mutant phenotype evidence) for activities confirmed by mutation studies

Completeness¶

The model is quite comprehensive, including all major enzymatic steps in the dTMP catabolic pathway.

Complex Representation¶

The model follows best practices for representing protein functions: - Each enzyme is represented as an individual activity rather than using complex IDs - This is appropriate since the specific activities of each component are known

Gene Product Usage¶

The model uses MGI identifiers for mouse gene products consistently and appropriately.

Minor Issues Identified¶

Missing Occurs_in Annotation: A few activities (NT5C3 and UPB1) are missing subcellular location information, though this is not crucial since the default location for these enzymes is the cytosol.
No Molecular Complex Representation: Though DPYD functions as a homodimer and UPB1 as homotetramer/homooctamer according to UniProt data, these are represented as monomeric activities. This is acceptable according to GO-CAM guidelines when the specific subunits carrying the activities are known.

Conclusion¶

The GO-CAM model "gomodel:5fadbcf000000942" is a well-constructed representation of the dTMP catabolic pathway in mouse. It accurately represents the sequential enzymatic steps, includes appropriate gene products, and follows GO-CAM best practices for causal connections, evidence attribution, and cellular location. The model provides a clear and biologically accurate view of the pathway that aligns well with current biochemical knowledge.

The biological content is robust and supported by literature evidence. The activities are connected in a way that is consistent with the known biochemical flow in this pathway. Overall, this model serves as a good example of how metabolic pathways should be represented in GO-CAM format.