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67086be200000363 cardiolipin metabolic process GO 0032048 Spom

Now, let me review the GO-CAM model gomodel:67086be200000363.

GO-CAM Model Review: gomodel:67086be200000363 (cardiolipin metabolic process in S. pombe)

Overview

This GO-CAM model (gomodel:67086be200000363) represents the cardiolipin biosynthetic pathway in fission yeast (Schizosaccharomyces pombe). The model details the enzymatic steps involved in the synthesis of cardiolipin, a unique phospholipid found in mitochondrial membranes that is essential for mitochondrial function.

Model Content and Structure

The model includes four key activities connected in a causal pathway:

  1. Phosphatidate cytidylyltransferase activity (GO:0004605)
  2. Enabled by: PomBase:SPBC1A4.06c (tam41)
  3. Occurs in: Mitochondrial matrix (GO:0005759)
  4. Part of: CDP-diacylglycerol biosynthetic process (GO:0016024)
  5. Has output: CDP-diacylglycerol (CHEBI:17962)

  6. Causally upstream of: CDP-diacylglycerol-glycerol-3-phosphate 3-phosphatidyltransferase activity

  7. CDP-diacylglycerol-glycerol-3-phosphate 3-phosphatidyltransferase activity (GO:0008444)

  8. Enabled by: PomBase:SPBP18G5.02 (pgs1)
  9. Occurs in: Mitochondrial matrix (GO:0005759)
  10. Part of: Cardiolipin biosynthetic process (GO:0032049)
  11. Has input: CDP-diacylglycerol (CHEBI:17962)

  12. Causally upstream of: Phosphatidylglycerophosphatase activity

  13. Phosphatidylglycerophosphatase activity (GO:0008962)

  14. Enabled by: PomBase:SPCC645.02 (gep4)
  15. Occurs in: Mitochondrial matrix (GO:0005759)
  16. Part of: Cardiolipin biosynthetic process (GO:0032049)

  17. Causally upstream of: Cardiolipin synthase (CMP-forming) activity

  18. Cardiolipin synthase (CMP-forming) activity (GO:0043337)

  19. Enabled by: PomBase:SPAC22A12.08c (crd1)
  20. Occurs in: Mitochondrial membrane (GO:0031966)
  21. Part of: Cardiolipin biosynthetic process (GO:0032049)
  22. Has output: Cardiolipin(2-) (CHEBI:62237)

Evidence Assessment

The model is well-supported by evidence: - Most activities are backed by direct experimental evidence (ECO:0000314) or sequence orthology evidence (ECO:0000266) - Key evidential support comes from PMID:31178220, PMID:9468529, and PMID:29958934 - From the literature (PMID:29958934) I was able to verify that SPAC22A12.08c indeed encodes the cardiolipin synthase in S. pombe, confirming a key element of the model

Evaluation of Causal Connections

The causal flow is well-represented: - All activities are appropriately connected using the "provides input for" (RO:0002413) predicate - The connections accurately represent the sequential enzymatic steps in cardiolipin biosynthesis - The inputs and outputs of reactions (specifically CDP-diacylglycerol and cardiolipin) are properly annotated

Anatomical Context

The model correctly localizes: - Most activities to the mitochondrial matrix (GO:0005759) - The final cardiolipin synthase activity to the mitochondrial membrane (GO:0031966)

This is consistent with the known localization of cardiolipin biosynthesis enzymes.

Issues Identified

  1. Minor redundancy issue: There is a duplicate "has_input" association for CHEBI:17962 (CDP-diacylglycerol) in the PomBase:SPBP18G5.02 activity node. One of these inputs lacks evidence information.

  2. Missing intermediate molecule: The model doesn't explicitly represent phosphatidylglycerol as an output of the phosphatidylglycerophosphatase activity and input to the cardiolipin synthase activity. This intermediate molecule should be included for complete pathway representation.

  3. Evidence consistency: There's inconsistent evidence attribution for some of the connections. For example, one of the "has_input" connections for CDP-diacylglycerol has no evidence indicated.

Recommendations

  1. Remove redundant input: Remove the duplicate input annotation for CDP-diacylglycerol or add appropriate evidence information.

  2. Add missing intermediate molecule: Add phosphatidylglycerol (PG) as:

  3. An output of the phosphatidylglycerophosphatase activity (PomBase:SPCC645.02)

  4. An input to the cardiolipin synthase activity (PomBase:SPAC22A12.08c)

  5. Ensure complete evidence: Add evidence information to all associations, particularly the missing evidence for one of the CDP-diacylglycerol inputs.

Overall Assessment

The model is generally well-constructed and accurately represents the cardiolipin biosynthetic pathway in S. pombe with good evidence support. It correctly identifies the key enzymatic steps, their causal relationships, and subcellular localization. The minor issues identified don't significantly affect the biological accuracy of the model but addressing them would improve its completeness and consistency.

The flow of the pathway is logical and follows the established understanding of cardiolipin biosynthesis, starting with the conversion of phosphatidic acid to CDP-diacylglycerol, then to phosphatidylglycerol phosphate, phosphatidylglycerol, and finally to cardiolipin. The evidence from published literature supports this representation.