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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; OMA:ACADVL - orthologs
Gene location (Human)
Chr.	Chromosome 17 (human)
End	7,225,266 bp
Gene location (Mouse)
Chr.	Chromosome 11 (mouse)
End	69,906,237 bp
RNA expression pattern
	Top expressed in
	right adrenal cortex; ; apex of heart; ; left adrenal cortex; ; anterior pituitary; ; right lobe of liver; ; right hemisphere of cerebellum; ; left lobe of thyroid gland; ; right lobe of thyroid gland; ; left ventricle; ; mucosa of transverse colon;
	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
	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
	37
	11370
	ENSG00000072778
	ENSMUSG00000018574
	P49748
	P50544
	NM_000018; NM_001033859; NM_001270447; NM_001270448
	NM_017366
	NP_000009; NP_001029031; NP_001257376; NP_001257377
	NP_059062
	Wikidata
View/Edit Human	View/Edit Mouse

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-acyl-CoA 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]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000072778 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000018574 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "acyl-CoA dehydrogenase, very long chain".
^ Strauss AW, Powell CK, Hale DE, Anderson MM, Ahuja A, Brackett JC, Sims HF (Nov 1995). "Molecular basis of human mitochondrial very-long-chain acyl-CoA dehydrogenase deficiency causing cardiomyopathy and sudden death in childhood". Proceedings of the National Academy of Sciences of the United States of America. 92 (23): 10496–500. Bibcode:1995PNAS...9210496S. doi:10.1073/pnas.92.23.10496. PMC 40638. PMID 7479827.
^ ^a ^b Zhou C, Blumberg B (Feb 2003). "Overlapping gene structure of human VLCAD and DLG4". Gene. 305 (2): 161–6. doi:10.1016/s0378-1119(02)01235-0. PMID 12609736.
^ Zhang LF, Ding JH, Yang BZ, He GC, Roe C (Dec 2003). "Characterization of the bidirectional promoter region between the human genes encoding VLCAD and PSD-95". Genomics. 82 (6): 660–8. doi:10.1016/s0888-7543(03)00211-8. PMID 14611808.
^ Aoyama T, Souri M, Ushikubo S, Kamijo T, Yamaguchi S, Kelley RI, Rhead WJ, Uetake K, Tanaka K, Hashimoto T (Jun 1995). "Purification of human very-long-chain acyl-coenzyme A dehydrogenase and characterization of its deficiency in seven patients". The Journal of Clinical Investigation. 95 (6): 2465–73. doi:10.1172/JCI117947. PMC 295925. PMID 7769092.
^ Pougovkina O, te Brinke H, Ofman R, van Cruchten AG, Kulik W, Wanders RJ, Houten SM, de Boer VC (Jul 2014). "Mitochondrial protein acetylation is driven by acetyl-CoA from fatty acid oxidation". Human Molecular Genetics. 23 (13): 3513–22. doi:10.1093/hmg/ddu059. PMID 24516071.
^ Andresen BS, Olpin S, Poorthuis BJ, Scholte HR, Vianey-Saban C, Wanders R, Ijlst L, Morris A, Pourfarzam M, Bartlett K, Baumgartner ER, deKlerk JB, Schroeder LD, Corydon TJ, Lund H, Winter V, Bross P, Bolund L, Gregersen N (Feb 1999). "Clear correlation of genotype with disease phenotype in very-long-chain acyl-CoA dehydrogenase deficiency". American Journal of Human Genetics. 64 (2): 479–94. doi:10.1086/302261. PMC 1377757. PMID 9973285.
^ Leslie, N. D.; Valencia, C. A.; Strauss, A. W.; Zhang, K.; Adam, M. P.; Ardinger, H. H.; Pagon, R. A.; Wallace, S. E.; Bean LJH; Stephens, K.; Amemiya, A. (1993). "Very Long-Chain Acyl-Coenzyme a Dehydrogenase Deficiency". PMID 20301763. {{cite journal}}: Cite journal requires |journal= (help)
^ "75 binary interactions found for search term ACADVL". IntAct Molecular Interaction Database. EMBL-EBI. Retrieved 2018-08-24.