ACADVL

ACADVL
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2UXW, 3B96
Identifiers
Aliases	ACADVL, acyl-CoA dehydrogenase, very long chain, ACAD6, LCACD, VLCAD, acyl-CoA dehydrogenase very long chain
External IDs	OMIM: 609575 MGI: 895149 HomoloGene: 5 GeneCards: ACADVL
Gene location (Human) Chr. Chromosome 17 (human)[1] Band 17p13.1 Start 7,217,125 bp[1] End 7,225,266 bp[1]
Gene location (Mouse) Chr. Chromosome 11 (mouse)[2] Band 11 B3|11 42.96 cM Start 69,901,009 bp[2] End 69,906,237 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in anterior pituitary right lobe of liver left lobe of thyroid gland right lobe of thyroid gland left ventricle body of pancreas body of stomach right uterine tube canal of the cervix gastrocnemius muscle Top expressed in myocardium of ventricle right ventricle cardiac muscles extraocular muscle digastric muscle soleus muscle intercostal muscle sternocleidomastoid muscle masseter muscle thoracic diaphragm More reference expression data BioGPS n/a
Gene ontology Molecular function oxidoreductase activity, acting on the CH-CH group of donors acyl-CoA dehydrogenase activity oxidoreductase activity flavin adenine dinucleotide binding long-chain-acyl-CoA dehydrogenase activity fatty-acyl-CoA binding very-long-chain-acyl-CoA dehydrogenase activity Cellular component membrane mitochondrial matrix nucleolus mitochondrion mitochondrial inner membrane mitochondrial nucleoid nucleus cytosol mitochondrial membranes Biological process epithelial cell differentiation negative regulation of fatty acid biosynthetic process lipid metabolism negative regulation of fatty acid oxidation energy derivation by oxidation of organic compounds fatty acid metabolic process regulation of cholesterol metabolic process IRE1-mediated unfolded protein response fatty acid beta-oxidation temperature homeostasis fatty acid catabolic process response to cold fatty acid beta-oxidation using acyl-CoA dehydrogenase Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 37 11370 Ensembl ENSG00000072778 ENSMUSG00000018574 UniProt P49748 P50544 RefSeq (mRNA) NM_000018 NM_001033859 NM_001270447 NM_001270448 NM_017366 RefSeq (protein) NP_000009 NP_001029031 NP_001257376 NP_001257377 NP_059062 Location (UCSC) Chr 17: 7.22 – 7.23 Mb Chr 11: 69.9 – 69.91 Mb PubMed search [3] [4]
Wikidata
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Very long-chain specific acyl-CoA dehydrogenase, mitochondrial (VLCAD) is an enzyme that in humans is encoded by the ACADVL gene.

Mutations in the ACADVL are associated with very long-chain acyl-coenzyme A dehydrogenase deficiency. The protein encoded by this gene is targeted to the inner mitochondrial membrane, where it catalyzes the first step of the mitochondrial fatty acid beta-oxidation pathway. This acyl-Coenzyme A dehydrogenase is specific to long-chain and very-long-chain fatty acids. A deficiency in this gene product reduces myocardial fatty acid beta-oxidation and is associated with cardiomyopathy. Alternative splicing results in multiple transcript variants encoding different isoforms.^[5]

Structure

The ACADVL gene contains 20 exons,^[6] and is about 5.4 kb long.^[7] VLCAD has interesting gene structure in humans, in that is located in a head-to-head structure with the DLG4 gene on Chromosome 17, and that the transcribed regions of these genes overlap. It has been shown that treatment with DEHP results in upregulation by the minimal promoter.^[8] While DLG4 and VLCAD share common regulatory elements, they each have separate and distinct tissue-specific elements that confer their function. In mice, these two genes are in a head-to-head orientation, but they do not overlap.^[7]

Function

The VLCAD enzyme catalyzes most of fatty acid beta-oxidation by forming a C2-C3 trans-double bond in the fatty acid. VLCAD is specific to very long-chain fatty acids, typically C16-acylCoA and longer.^[9] In mice that have VLCAD deficiency, there is little to no protein hyperacetylation in the liver; this implies that the VLCAD protein is also necessary for protein acetylation in this biological system.^[10]

Clinical significance

ACADVL is linked with very long-chain acyl-coenzyme A dehydrogenase deficiency (VLCADD), which has many symptoms, and typically presents as one of three phenotypes. The first is severe, with an early childhood onset and high mortality rate; the most common symptom is this form is cardiomyopathy. The second is a late onset childhood form, with milder symptoms that present most commonly as hypoketotic hypoglycemia. The final form presents in adulthood, and presents as isolated skeletal muscle involvement, rhabdomyolysis, and myoglobinuria, which is triggered by exercise or fasting.^[11] The disease is typically diagnosed by first performing tandem mass spectrometry on a blood sample of the patient during a period of stress, and then performing molecular genetic testing for the presence of the ACADVL gene. The deficiency is treated systematically, but certain conditions such as fasting, myocardial irritation, dehydration, and high fat diets are avoided in an attempt to prevent secondary complications.^[12]

Interactions

ACADVL has been shown to have 75 binary protein-protein interactions including 73 co-complex interactions. ACADVL appears to interact with RPSA and GPHN.^[13]

See also

• Acyl CoA dehydrogenase

References

Further reading

External links

• GeneReviews/NCBI/NIH/UW entry on Very long-chain acyl-coenzyme A dehydrogenase deficiency
• Human ACADVL genome location and ACADVL gene details page in the UCSC Genome Browser.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.