Skip to content

5fa76ad400000018 AMP catabolic process 2 Mouse

Now let me review the GO-CAM model based on all the information I've gathered:

GO-CAM Review: AMP catabolic process 2 (Mouse) - gomodel:5fa76ad400000018

Model Overview

This GO-CAM model (gomodel:5fa76ad400000018) represents the AMP catabolic process in mouse, focusing on enzymes and transporters involved in adenine nucleotide metabolism. The model includes:

  1. 5'-nucleotidase (CD73/Nt5e) activity
  2. ADP phosphatase (ENTPD1) activity
  3. AMP deaminase (AMPD3) activity
  4. Nucleoside transporters (SLC29A1 and SLC29A2)

Biological Accuracy Assessment

The model is well-supported by the literature with strong evidence from:

  • PMID:28746349 - Details the regulation of adenine nucleotide pool in erythrocytes, demonstrating how CD73, AMPD3, and nucleoside transporters coordinate in AMP metabolism
  • PMID:28069792 - Referenced for the nucleoside transporter activities
  • PMID:17502665 - Supporting ENTPD1 function

The protein functions represented align with their established biochemical roles:

  1. Nt5e (CD73) - Correctly represented as having 5'-nucleotidase activity converting AMP to adenosine, with annotation for its extracellular location on the plasma membrane.

  2. ENTPD1 - Properly annotated with ADP phosphatase activity, converting ADP to AMP.

  3. SLC29A1/SLC29A2 - Correctly annotated as purine nucleoside transporters.

  4. AMPD3 - Correctly assigned AMP deaminase activity.

The causal relationships between activities are biologically accurate, reflecting how: - ENTPD1 generates AMP that feeds into CD73 activity - CD73-generated adenosine is transported by SLC29A1/SLC29A2 - ENTPD1 also provides input for SLC29A1 activity

Structural Assessment

The structure of the model follows GO-CAM best practices:

  1. Activities are properly defined with molecular functions, cellular locations, and inputs/outputs where appropriate:
  2. CD73 activity has AMP as input and adenosine as output

  3. ENTPD1 has ADP as input and AMP as output

  4. Causal connections are correctly established using "provides input for" (RO:0002413) predicates:

  5. The ADP phosphatase activity (ENTPD1) provides input for 5'-nucleotidase activity (CD73)
  6. The ADP phosphatase activity provides input for nucleoside transport

  7. The 5'-nucleotidase activity provides input for nucleoside transport

  8. Cellular locations are appropriately specified:

  9. CD73 is correctly annotated to the external side of plasma membrane (GO:0009897)
  10. SLC29A1 and SLC29A2 are correctly annotated to the plasma membrane
  11. AMPD3 is correctly annotated to the cytosol

Areas for Improvement

While the model is generally well-constructed, I have identified a few areas for improvement:

  1. Subcellular localization for one activity:

  2. AMPD3 (gomodel:5fa76ad400000018/5fa76ad400000044) is annotated with GO:0005829 (cytosol) but lacks evidence citations for this annotation.

  3. Causal relationships could be more precise:

  4. There could be a causal relationship from CD73 (Nt5e) to the AMPD3 activity to reflect the competition for AMP as a substrate, which would complete the pathway representation.

  5. Additional activities:

  6. The model could include the activity of adenosine kinase, which would complete the adenosine-AMP cycle by phosphorylating adenosine back to AMP.

  7. Adenosine deaminase (ADA) activity could be included to represent the alternative fate of adenosine.

  8. Regulatory relationships:

  9. The model doesn't include any regulatory relationships (RO:0002629/RO:0002630 - direct positive/negative regulation). From the literature, there are known regulatory interactions between these components that could be included.

Conclusion

Overall, this GO-CAM model is a well-constructed, accurate representation of the AMP catabolic process in mouse. It includes appropriate molecular functions, cellular locations, biological processes, and causal connections with strong evidence support. The activities and relationships represented in the model are consistent with the current understanding of adenine nucleotide metabolism as demonstrated in the literature.

The model successfully shows how ADP is converted to AMP by ENTPD1, then either dephosphorylated to adenosine by CD73 or deaminated to IMP by AMPD3. It also shows how adenosine is transported across the membrane by nucleoside transporters.

The few suggested improvements would enhance the comprehensiveness of the model but do not detract from its current accuracy and utility.