ACADM

ACADM
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1EGC, 1EGD, 1EGE, 1T9G, 2A1T, 4P13
Identifiers
Aliases	ACADM, acyl-CoA dehydrogenase, C-4 to C-12 straight chain, ACAD1, MCAD, MCADH, acyl-CoA dehydrogenase medium chain
External IDs	OMIM: 607008 MGI: 87867 HomoloGene: 3 GeneCards: ACADM
Gene location (Human) Chr. Chromosome 1 (human)[1] Band 1p31.1 Start 75,724,431 bp[1] End 75,787,575 bp[1]
Gene location (Mouse) Chr. Chromosome 3 (mouse)[2] Band 3 H3|3 78.77 cM Start 153,627,994 bp[2] End 153,650,269 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in jejunal mucosa biceps brachii right ventricle body of tongue vastus lateralis muscle renal medulla kidney tubule gastrocnemius muscle left ventricle myocardium Top expressed in right ventricle myocardium of ventricle brown adipose tissue kidney soleus muscle extraocular muscle digastric muscle cardiac muscles thoracic diaphragm sternocleidomastoid muscle 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 identical protein binding oxidoreductase activity medium-chain-acyl-CoA dehydrogenase activity flavin adenine dinucleotide binding Cellular component axon mitochondrion extracellular exosome nucleus nuclear speck mitochondrial matrix mitochondrial membranes Biological process medium-chain fatty acid metabolic process lipid metabolism fatty acid beta-oxidation using acyl-CoA dehydrogenase fatty acid metabolic process metabolism carnitine biosynthetic process medium-chain fatty acid catabolic process carnitine metabolic process, CoA-linked fatty acid beta-oxidation regulation of lipid metabolic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 34 11364 Ensembl ENSG00000117054 ENSMUSG00000062908 UniProt P11310 P45952 RefSeq (mRNA) NM_000016 NM_001127328 NM_001286042 NM_001286043 NM_001286044 NM_007382 RefSeq (protein) NP_000007 NP_001120800 NP_001272971 NP_001272972 NP_001272973 NP_031408 Location (UCSC) Chr 1: 75.72 – 75.79 Mb Chr 3: 153.63 – 153.65 Mb PubMed search [3] [4]
Wikidata
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ACADM (acyl-Coenzyme A dehydrogenase, C-4 to C-12 straight chain) is a gene that provides instructions for making an enzyme called acyl-coenzyme A dehydrogenase that is important for breaking down (degrading) a certain group of fats called medium-chain fatty acids.

These fatty acids are found in foods such as milk and certain oils, and they are also stored in the body's fat tissue. Medium-chain fatty acids are also produced when larger fatty acids are degraded.

The acyl-coenzyme A dehydrogenase for medium-chain fatty acids (ACADM) enzyme is essential for converting these particular fatty acids to energy, especially during periods without food (fasting). The ACADM enzyme functions in mitochondria, the energy-producing centers within cells. It is found in the mitochondria of several types of tissues, particularly the liver.

The ACADM gene is located on the short (p) arm of chromosome 1 at position 31, from base pair 75,902,302 to base pair 75,941,203.

Structure

The protein encoded by the ACADM gene is ~47 kDa in size, and composed of 421 amino acids.^[5]

Function

The LCAD enzyme catalyzes most of fatty acid beta-oxidation by forming a C2-C3 trans-double bond in the fatty acid. MCAD works on long-chain fatty acids, typically between C4 and C12-acylCoA.^[6] Fatty acid oxidation has proven to spare glucose in fasting conditions, and is also required for amino acid metabolism, which is essential for the maintenance of adequate glucose production.^[7] Furthermore, MCAD participates in fatty acid metabolism and PPAR signaling pathway.^[8]

Clinical significance

Medium-chain acyl-coenzyme A dehydrogenase deficiency can be caused by mutations in the ACADM gene. More than 54 ACADM gene mutations that cause medium-chain acyl-coenzyme A dehydrogenase deficiency have been identified.^[9] Many of these mutations switch an amino acid building block in the ACADM enzyme. The most common amino acid substitution replaces lysine with glutamic acid at position 329 in the enzyme's chain of amino acids (also written as Lys329Glu or K329E).^[10] This mutation and other amino acid substitutions alter the enzyme's structure, reducing or abolishing its activity. Other mutations delete or duplicate part of the ACADM gene, which leads to an unstable enzyme that cannot function.

With a shortage (deficiency) of functional ACADM enzyme, medium-chain fatty acids cannot be degraded and processed. As a result, these fats are not converted into energy, which can lead to characteristic symptoms of this disorder, such as lack of energy (lethargy) and low blood sugar. Levels of medium-chain fatty acids or partially degraded fatty acids may build up in tissues and can damage the liver and brain, causing more serious complications.^[11]

References

Further reading

External links

• GeneReviews/NIH/NCBI/UW entry on Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency
• GeneCard
• ACADM at The GDB Human Genome Database
• Human ACADM genome location and ACADM gene details page in the UCSC Genome Browser.