| Claim | Evidence type | Key quantitative/statistical details | Source (citation id + DOI URL + pub month/year) |
|---|---|---|---|
| **Identity/function:** zebrafish **cpt2** is the Danio rerio ortholog of human **CPT2** and participates in mitochondrial long-chain fatty-acid β-oxidation by converting long-chain acylcarnitines to acyl-CoA. | Zebrafish experiment + comparative annotation | Zebrafish/human sequence homology reported as **~70.9%**; morpholino knockdown caused abnormal lipid utilization/deposition and neurodevelopmental defects, supporting conserved CPT2 function. | Baker et al. 2024, Biomolecules, Jul 2024, https://doi.org/10.3390/biom14080914 (pqac-00000000, pqac-00000005) |
| **Localization:** CPT2 is a mitochondrial protein detected in zebrafish mitochondrial fractions, consistent with inner-mitochondrial-membrane carnitine-shuttle localization. | Zebrafish experiment | CPT2 protein measured in **mitochondrial fractions** from larvae; Western blot showed zebrafish CPT2 migrating near **~80 kDa**. | Baker et al. 2024, Biomolecules, Jul 2024, https://doi.org/10.3390/biom14080914 (pqac-00000001, pqac-00000003, pqac-00000008) |
| **Loss of function in zebrafish:** cpt2 knockdown impairs carnitine-shuttle flux and causes long-chain acylcarnitine accumulation. | Zebrafish experiment | Translation-blocking MO reduced CPT2 protein by **~31% vs CTRL** (~38% vs WT); splice-blocking MO reduced CPT2 by **~78% vs CTRL** (~85% vs WT). Total acylcarnitines increased **~70% (TB, p<0.001)** and **~42% (SB, p≤0.05)** vs WT; long-chain species including **C16, C18, C18:1** increased. | Baker et al. 2024, Biomolecules, Jul 2024, https://doi.org/10.3390/biom14080914 (pqac-00000001, pqac-00000002, pqac-00000019) |
| **Phenotype in zebrafish:** cpt2 deficiency disrupts development, especially neural and lipid-handling phenotypes. | Zebrafish experiment | Viability at 1 dpi with 0.5 mM MOs was similar to WT (**WT 77%, CTRL 84%, TB 74%, SB 79%**), enabling mild–moderate deficiency modeling. Knockdown caused reduced body size, curved tails, pericardial edema, enlarged ventricles, abnormal brain development, altered swimming/electrical activity, and increased schizophrenia-associated gene expression. | Baker et al. 2024, Biomolecules, Jul 2024, https://doi.org/10.3390/biom14080914 (pqac-00000000, pqac-00000002, pqac-00000019, pqac-00000020) |
| **Canonical reaction/pathway:** CPT2 reconverts fatty acylcarnitine to fatty acyl-CoA + L-carnitine at the inner mitochondrial membrane as part of the carnitine shuttle. | Recent review | Places CPT2 at the **inner mitochondrial membrane**; defines role after CACT-mediated transport so acyl-CoA can enter matrix β-oxidation. | Duan et al. 2024, Biology, Nov 2024, https://doi.org/10.3390/biology13110892 (pqac-00000004, pqac-00000015) |
| **Substrate specificity/topology:** CPT2 behaves as a matrix-facing, inner-membrane-associated carnitine acyltransferase with preference for medium/long-chain substrates. | Recent review | Reported as catalytically active toward **mid-length and long-chain acyl-CoA esters**, with little/no activity toward **short-chain** or **ultralong-chain** substrates; described as more lightly attached to the inner membrane and matrix-protein-like. | Duan et al. 2024, Biology, Nov 2024, https://doi.org/10.3390/biology13110892 (pqac-00000007, pqac-00000013) |
| **Carnitine-shuttle context:** CPT2 works with CPT1 and CACT to regenerate acyl-CoA on the matrix side of the inner membrane for β-oxidation. | Review | Describes CPT-II as an **IMM protein** converting transesterified acylcarnitines into acyl-CoA and releasing carnitine for CACT-mediated return; emphasizes LCFA transport into mitochondria. | Yao et al. 2023, World J Gastroenterol, Mar 2023, https://doi.org/10.3748/wjg.v29.i12.1765 (pqac-00000011) |
| **Mechanistic/structural support:** CPT2 contains distinct CoA-, acyl-, and carnitine-binding sites and lacks the membrane-anchoring N-terminus typical of CPT1. | Foundational high-authority review | Crystal-structure summary identifies a **Y-shaped tunnel** with separate CoA/acyl/carnitine sites; key catalytic/binding residues include **His372, Tyr486, Ser488, Thr499, Ser590**; CPT2 is shorter than CPT1 (**658 vs 773 aa**) and operates on the matrix side of the inner membrane. | Ceccarelli et al. 2011, J Med Chem, Apr 2011, https://doi.org/10.1021/jm100809g (pqac-00000012, pqac-00000014) |
| **Broader acyltransferase family inference:** CPT2 is a carnitine acyltransferase specialized for long-chain fatty acyl groups. | Recent review | Review states CPT1/CPT2 are specific for **long-chain fatty acyl-CoAs (C8–C18)** and highlights crystallized CPT2 with **CoA and palmitate**. | Volpicella et al. 2025, Biomolecules, Feb 2025, https://doi.org/10.3390/biom15020216 (pqac-00000016, pqac-00000017) |
| **System-level zebrafish application:** environmental PFOS exposure perturbs the carnitine shuttle and fatty-acid oxidation in embryo-larval zebrafish, supporting the pathway context in which cpt2 functions. | Zebrafish systems biology / real-world implementation | In silico zebrafish metabolic model contained **12,909 reactions**; PFOS parameterization at **0.06, 0.6, and 2 µM** predicted fatty-acid/fatty-acyl-CoA pool flux increases by **almost an order of magnitude**; human-linked PFOS effects noted at **≤200 ng/mL (≤0.4 µM)**. | Nolen et al. 2024, Front. Syst. Biol., Mar 2024, https://doi.org/10.3389/fsysb.2024.1367562 (pqac-00000021) |
| **Nutritional/metabolic implementation in zebrafish:** boosting the carnitine pool enhances mitochondrial β-oxidation and reduces tissue lipid deposition, consistent with higher flux through the CPT shuttle in which CPT2 acts downstream of CPT1. | Zebrafish dietary experiment | Dietary L-carnitine significantly increased tissue free/total carnitine, significantly decreased liver and muscle TG, and significantly increased mitochondrial and total β-oxidation capacity in liver (feeding and fasting) and muscle (feeding); assays reported **n=4 or n=6**, significance **P<0.05/P<0.01**. CPT1 mRNA increased, while lipogenesis genes decreased. | Li et al. 2017, Sci Rep, Jan 2017, https://doi.org/10.1038/srep40815 (pqac-00000022, pqac-00000023, pqac-00000025) |


*Table: This table summarizes the core functional annotation evidence for Danio rerio cpt2 / UniProt Q5U3U3, integrating direct zebrafish experiments with authoritative reviews on CPT2 biochemistry and localization. It is useful for separating species-specific evidence from conserved mechanistic inference.*