Notes for DANRE ldhd

2026-05-09 review notes

• Core function is mitochondrial FAD-dependent D-lactate dehydrogenase activity in lactate catabolism [file:DANRE/ldhd/ldhd-uniprot.txt "acts specifically on D-lactate, not on its stereoisomer L-lactate"].
• Generic catalytic activity was modified to the specific D-lactate dehydrogenase and (2R)-2-hydroxycarboxylate dehydrogenase terms [file:DANRE/ldhd/ldhd-uniprot.txt "Reaction=(R)-lactate + FAD + H(+) = FADH2 + pyruvate"].
• FAD/flavin binding terms are kept as non-core cofactor annotations [file:DANRE/ldhd/ldhd-uniprot.txt "FAD-binding PCMH-type"].

Re-review 2026-09-29

• Resolved the six PENDING rows added from the refreshed GOA (IBA mitochondrion, IBA D-lactate dehydrogenase (cytochrome), IBA D-lactate dehydrogenase (NAD+), IBA FAD binding, and the two GO_REF:0000120 Rhea-mapped IEA rows). Removed the two stale GO_REF:0000116 IEA rows that no longer exist in GOA, and updated the GO:0140174 label to the current GOA/ontology label "(2R)-2-hydroxycarboxylate dehydrogenase (FAD) activity".
• GO:0004458 D-lactate dehydrogenase (cytochrome) activity (IBA) -> ACCEPT: human LDHD was shown in 2024 to pass electrons from D-lactate directly to cytochrome c PMID:38413804, and LDHD-knockout cells lose the D-lactate-driven membrane-potential response PMID:38413804. The PAINT node (yeast DLD1 / plant DLD / vertebrate LDHD) is therefore sound.
• GO:0008720 D-lactate dehydrogenase (NAD+) activity (IBA) -> MODIFY to GO:0140170 with a propagation_review: the only experimental donor is Arabidopsis AT5G06580 (IMP, PMID:22155004, a selection-marker study); NAD-dependent D-LDHs are a distinct bacterial family PMID:37863926, whereas LDHD is FAD/Mn2+-dependent PMID:37863926.
• All D-lactate/(2R)-2-hydroxycarboxylate dehydrogenase (FAD) rows (EXP, ISS, IEA) and lactate catabolic process (IMP, IBA) ACCEPTED on the zebrafish mutant evidence [PMID:30931947 "metabolic analysis revealed elevated levels of D-lactate, but not L-lactate, in ldhd−/− larvae compared to wildtype"; "ldhd−/− uninjected embryos showed a significant D-lactate increase that was restored to baseline levels by mRNA microinjection of the wildtype LDHD sequence"]. FAD-binding rows kept as non-core. Deep-research quotes replaced by primary-literature quotes; PMID:37863926 and PMID:38413804 added with reference_review.
• Description rewritten as standalone biology; second core-function entry added for the cytochrome-coupled activity; suggested question/experiment added on the zebrafish electron acceptor.

Follow-up after PR review (2026-10-04)

PMID:22155004 (Wienstroer et al. 2012, abstract-only), the experimental source behind the Arabidopsis AT5G06580 donor of the GO:0008720 IBA, is now cached and listed in references with a reference_review, and the GO:0008720 row quotes it directly PMID:22155004. The abstract confirms the annotation rests on a D-lactate-tolerance selection-marker phenotype rather than NAD+-dependent kinetics, so the SOURCE_WEAK_OR_INFERRED call is now checkable.