L-carnitine carries long-chain fatty acids into mitochondria for beta-oxidation. In animals it is made from N6,N6,N6-trimethyllysine, released by degradation of proteins carrying methylated lysines, in four steps. Trimethyllysine dioxygenase (Tmlh) hydroxylates trimethyllysine to 3-hydroxy-trimethyllysine; an aldolase cleaves this to 4-trimethylaminobutyraldehyde and glycine; an aldehyde dehydrogenase oxidizes the aldehyde to gamma-butyrobetaine; and gamma-butyrobetaine dioxygenase hydroxylates gamma-butyrobetaine to carnitine. In Drosophila, CG10814 is the homolog of gamma-butyrobetaine dioxygenase, and the aldolase step is attributed to the threonine-aldolase-like protein CG10184 and to serine hydroxymethyltransferase (Shmt), which in mammals has hydroxytrimethyllysine aldolase activity.
Boundary. The module covers the four FlyBase members. The 4-trimethylaminobutyraldehyde dehydrogenase step has no FlyBase member and is represented only in the connection between the aldolase and hydroxylase steps. Catalytic functions are assigned only to Tmlh; CG10184, Shmt and CG10814 carry no function in this module because their carnitine-pathway activities have not been shown for the fly proteins. Shmt is also a part of the glycine biosynthesis module. FlyBase groups realized by this module: CARNIBI (FBgg0002240). Participants were generated from the FlyBase gene-group membership and mapped to UniProtKB by projects/FLYBASE_GENE_GROUPS/generate_modules.py from module_specs/dmel_carnitine_biosynthesis.yaml. Member genes with a gene review in this repository: CG10184, CG10814, Shmt, Tmlh.
All recommended fields populated.
✗ none found
No MODULE:dmel_carnitine_biosynthesis deep-research report alongside the module YAML.
✓ every leaf node grounds to a representative protein.
✓ every declared conforms_to bundle matches its template motif.
✓ every PRECEDES step chains, or its break is acknowledged via chaining_status.
1 gene-function check(s) reflected in core functions · 0 conflict(s) · 0 evidence or coverage gap(s) (1 comparison(s))
Retained noncore functions are reported separately; they do not require promotion to core functions. Support from representative genes does not establish conservation across the whole family. Missing reviews or identifiers leave a claim unverified.
| Annoton | Participant | Function | Assessment |
|---|---|---|---|
| trimethyllysine_hydroxylation_tmlh | Tmlh UniProtKB:Q9VDM7 Gene |
trimethyllysine dioxygenase activity GO:0050353 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
4 complete review(s) · 4 with deep research · 0 missing review · 0 reviewed but lacking deep research
| Gene | Review | Complete | Deep research |
|---|---|---|---|
| CG10184 Q9VCK6 | ✓ | ✓ | ✓ |
| CG10814 A1Z9C1 | ✓ | ✓ | ✓ |
| Shmt Q9W457 | ✓ | ✓ | ✓ |
| Tmlh Q9VDM7 | ✓ | ✓ | ✓ |
Four-step conversion of trimethyllysine to carnitine via Tmlh, an aldolase (CG10184 or Shmt) and the gamma-butyrobetaine dioxygenase homolog CG10814.
Candidate aldolases assigned to this step by FlyBase; neither has been shown biochemically to perform it in Drosophila.
CG10814 is a TauD-family 2-oxoglutarate-dependent hydroxylase with the gamma-butyrobetaine hydroxylase-like N-terminal domain.