Acadvl (CG7461; dACADVL) is the Drosophila melanogaster ortholog of human very-long-chain specific acyl-CoA dehydrogenase (VLCAD). It is an FAD-dependent flavoenzyme of the acyl-CoA dehydrogenase (ACAD) family that catalyzes the first, committed step of each cycle of mitochondrial fatty acid beta-oxidation: the stereospecific alpha,beta-dehydrogenation of saturated and unsaturated acyl-CoA thioesters, producing the corresponding trans-2-enoyl-CoA and transferring the abstracted electrons to the electron-transfer flavoprotein (ETF). Like its mammalian counterpart it acts specifically on long-chain and very-long-chain fatty acyl-CoAs (primary chains of roughly 12 to 24 carbons, e.g. palmitoyl-CoA, C16), distinguishing it from the medium- and short-chain acyl-CoA dehydrogenases. The protein carries the characteristic ACAD N-terminal, middle and C-terminal domains together with the extra ACAD9/ACADVL-type C-terminal extension, is FAD-dependent, and is a homodimer that associates as a peripheral protein with the matrix face of the mitochondrial inner membrane. Through this activity Acadvl feeds long-chain dietary and stored fatty acids into beta-oxidation for the production of acetyl-CoA and cellular energy.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0017099 very-long-chain fatty acyl-CoA dehydrogenase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetically inferred very-long-chain acyl-CoA dehydrogenase activity (PANTHER PTN000856877, whose leaves include the experimentally characterized human VLCAD P49748). This is the defining catalytic activity of the VLCAD family and, together with the CDD VLCAD hit (cd01161) and the PANTHER subfamily assignment (PTHR43884:SF11, very long-chain specific acyl-CoA dehydrogenase), is well supported at this specific level for the fly ortholog. This captures the core molecular function. Reason: The IBA call is grounded in a tree whose experimental leaves (human ACADVL) directly demonstrate very-long-chain acyl-CoA dehydrogenase activity, and the fly protein carries the VLCAD-specific domain architecture and subfamily assignment. UniProt assigns EC 1.3.8.9 (very-long-chain) to this protein. Supporting Evidence: file:DROME/Acadvl/Acadvl-uniprot.txt very long-chain specific acyl-CoA dehydrogenase acts specifically on |
| GO:0000062 fatty-acyl-CoA binding | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetically inferred binding of the acyl-CoA substrate. VLCAD-family enzymes must bind fatty-acyl-CoA thioesters in order to dehydrogenate them, so this annotation is correct but ancillary (a prerequisite of the catalytic activity rather than a separate core function). Reason: Substrate binding is subsumed by the catalytic dehydrogenase activity, which better represents the core molecular function; retained as a supporting non-core annotation. Supporting Evidence: file:DROME/Acadvl/Acadvl-uniprot.txt acts specifically on fatty acyl-CoAs |
| GO:0003995 acyl-CoA dehydrogenase activity | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro-based electronic annotation (IPR006089) to the general acyl-CoA dehydrogenase activity term. The protein contains the ACAD active-site signature (PROSITE PS00072/PS00073) and is a bona fide family member, so the term is correct but broader than the specific VLCAD/LCAD activities that are also annotated. Reason: Correct general parent term subsumed by the specific GO:0017099 (very-long-chain) and GO:0004466 (long-chain) activities used as core; retained as a supporting non-core annotation. Supporting Evidence: file:DROME/Acadvl/Acadvl-uniprot.txt Belongs to the acyl-CoA dehydrogenase family. |
| GO:0004466 long-chain fatty acyl-CoA dehydrogenase activity | IEA GO_REF:0000003 | ACCEPT | Summary: Electronic annotation from EC mapping (EC 1.3.8.8) derived from UniProt. In addition to its very-long-chain activity, VLCAD has well-documented long-chain acyl-CoA dehydrogenase activity (classically assayed with palmitoyl-CoA, C16), so this is a valid and biologically accurate term for the fly ortholog. Reason: UniProt assigns EC 1.3.8.8 (long-chain acyl-CoA dehydrogenase, RHEA:17721) to this protein and it acts on fatty acyl-CoAs down to ~12 carbons. Consistent with the ISS annotation to the same term. Supporting Evidence: file:DROME/Acadvl/Acadvl-uniprot.txt a long-chain 2,3-saturated fatty acyl-CoA + oxidized |
| GO:0005743 mitochondrial inner membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Electronic annotation from UniProt subcellular-location mapping. VLCAD-family enzymes are peripheral proteins of the mitochondrial inner membrane, distinguishing them from the soluble matrix ACADs; UniProt records mitochondrion inner membrane, peripheral membrane protein. This is the core cellular localization. Reason: Inner-membrane association is a conserved feature of VLCAD; UniProt records the inner-membrane, peripheral-membrane localization for this protein. Supporting Evidence: file:DROME/Acadvl/Acadvl-uniprot.txt Mitochondrion inner membrane |
| GO:0006631 fatty acid metabolic process | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ARBA electronic annotation placing Acadvl in fatty acid metabolism. Correct, but this is a broad parent of the specific fatty acid beta-oxidation process that the enzyme actually performs. Reason: Correct but general; subsumed by the more specific beta-oxidation process (GO:0033539) used as the core biological process. Retained as non-core. Supporting Evidence: file:DROME/Acadvl/Acadvl-uniprot.txt Lipid metabolism; mitochondrial fatty acid beta-oxidation. |
| GO:0016627 oxidoreductase activity, acting on the CH-CH group of donors | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro-based annotation to the intermediate oxidoreductase term. The acyl-CoA dehydrogenase reaction introduces a double bond between the alpha and beta carbons (oxidation of a CH-CH group), so this term is accurate at an appropriate intermediate level. Reason: Correct intermediate parent between general oxidoreductase activity and the specific acyl-CoA dehydrogenase activities, which are the core molecular functions. Supporting Evidence: file:DROME/Acadvl/Acadvl-uniprot.txt Belongs to the acyl-CoA dehydrogenase family. |
| GO:0017099 very-long-chain fatty acyl-CoA dehydrogenase activity | IEA GO_REF:0000003 | ACCEPT | Summary: Electronic annotation from EC mapping (EC 1.3.8.9). This is the defining catalytic activity of VLCAD and is redundant with the IBA and ISS annotations to the same term, so the electronic call is correct and represents the core molecular function. Reason: Correct and identical to the core VLCAD-activity term captured by the IBA annotation; the EC 1.3.8.9 assignment independently supports the very-long-chain acyl-CoA dehydrogenase activity. Supporting Evidence: file:DROME/Acadvl/Acadvl-uniprot.txt a very-long-chain 2,3-saturated fatty acyl-CoA + oxidized |
| GO:0050660 flavin adenine dinucleotide binding | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro-based annotation for FAD binding. Acadvl is an FAD-containing flavoprotein; FAD is the obligate redox cofactor of all acyl-CoA dehydrogenases (UniProt COFACTOR: FAD). The term is correct and corresponds to a core feature of the enzyme. Reason: FAD is the essential prosthetic group of VLCAD-family enzymes; UniProt lists FAD (ChEBI:CHEBI:57692) as the cofactor and flags the protein as a flavoprotein. Supporting Evidence: file:DROME/Acadvl/Acadvl-uniprot.txt Name=FAD; Xref=ChEBI:CHEBI:57692; |
| GO:0005739 mitochondrion | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS annotation transferred by FlyBase from the human ortholog UniProtKB:P49748 (VLCAD). Mitochondrial localization is unquestionably correct for Acadvl but is less specific than the inner-membrane annotation. Reason: Correct mitochondrial localization (the enzyme is imported into the mitochondrion) but subsumed by the more specific GO:0005743 inner-membrane annotation; retained as non-core. Supporting Evidence: file:DROME/Acadvl/Acadvl-uniprot.txt Homodimerizes after import into the mitochondrion. |
| GO:0004466 long-chain fatty acyl-CoA dehydrogenase activity | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation transferred by FlyBase from human VLCAD (P49748), whose long-chain acyl-CoA dehydrogenase activity (EC 1.3.8.8, palmitoyl-CoA/C16) is directly demonstrated. The term is correct for the fly ortholog and duplicates the EC-based IEA annotation. Reason: Correct long-chain acyl-CoA dehydrogenase activity, consistent with the EC-derived IEA annotation to the same term and with the experimentally characterized human ortholog. Supporting Evidence: file:DROME/Acadvl/Acadvl-uniprot.txt a long-chain 2,3-saturated fatty acyl-CoA + oxidized |
| GO:0017099 very-long-chain fatty acyl-CoA dehydrogenase activity | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation transferred by FlyBase from human VLCAD (P49748). This is the defining catalytic activity, well supported for the human source and consistent with the fly protein VLCAD subfamily assignment; redundant with the IBA and EC-based annotations to the same term. Reason: Correct and identical to the core VLCAD-activity term captured by the IBA annotation; the homology transfer from the experimentally characterized human ortholog supports it. Supporting Evidence: file:DROME/Acadvl/Acadvl-uniprot.txt a very-long-chain 2,3-saturated fatty acyl-CoA + oxidized |
| GO:0033539 fatty acid beta-oxidation using acyl-CoA dehydrogenase | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation transferred by FlyBase from human VLCAD (P49748). This is precisely the process Acadvl performs: it catalyzes the acyl-CoA dehydrogenase step of mitochondrial fatty acid beta-oxidation. Core biological process. Reason: VLCAD-family enzymes catalyze the first (dehydrogenation) step of mitochondrial fatty acid beta-oxidation; UniProt records the pathway lipid metabolism, mitochondrial fatty acid beta-oxidation for this protein. Supporting Evidence: file:DROME/Acadvl/Acadvl-uniprot.txt catalyze the first step of mitochondrial |
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Download this section (compressed HTML)Q: In Drosophila, is CG7461/Acadvl the sole ortholog covering both the VLCAD and ACAD9 functions of the mammalian clade (the protein carries the ACAD9/ACADVL-type C-terminal domain), and if so does it also participate in mitochondrial respiratory-chain complex I assembly as mammalian ACAD9 does?
Q: What is the physiological substrate-chain-length profile of Acadvl in fly tissues, and how is long-chain fatty acid oxidation partitioned between Acadvl and the other fly acyl-CoA dehydrogenases across the fed, starved, and flight-muscle-active states?
Experiment: Generate an Acadvl (CG7461) loss-of-function allele (or RNAi knockdown) and measure whole-animal and tissue acylcarnitine/acyl-CoA profiles by mass spectrometry under fed and starved conditions, testing for accumulation of long-chain species characteristic of a VLCAD block.
Hypothesis: Loss of Acadvl impairs long-chain fatty acid beta-oxidation in Drosophila, producing accumulation of long-chain acylcarnitines and reduced starvation resistance, mirroring mammalian VLCAD deficiency.
Experiment: Enzymatically characterize recombinant Drosophila Acadvl with a panel of acyl-CoA substrates of varying chain length (C8-C24) using an ETF- or ferricenium-based dehydrogenase assay, and test FAD dependence.
Hypothesis: Drosophila Acadvl has maximal acyl-CoA dehydrogenase activity toward long- and very-long-chain substrates (C14-C24) and requires bound FAD, confirming conservation of VLCAD substrate specificity.
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