ACADM (acyl-Coenzyme A dehydrogenase, C-4 to C-12 straight chain) is a
gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
that provides instructions for making an enzyme called
acyl-coenzyme A dehydrogenase Acyl-CoA dehydrogenases (ACADs) are a class of enzymes that function to catalyze the initial step in each cycle of fatty acid β-oxidation in the mitochondria of cells. Their action results in the introduction of a trans double-bond between C2 (� ...
that is important for breaking down (degrading) a certain group of fats called
medium-chain fatty acid
Medium-chain triglycerides (MCTs) are triglycerides with two or three fatty acids having an aliphatic tail of 6–12 carbon atoms, i.e. medium-chain fatty acids (MCFAs). Rich food sources for commercial extraction of MCTs include palm kernel oil a ...
s.
These
fatty acid
In chemistry, particularly in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, ...
s are found in foods such as
milk
Milk is a white liquid food produced by the mammary glands of mammals. It is the primary source of nutrition for young mammals (including breastfed human infants) before they are able to digest solid food. Immune factors and immune-modulati ...
and certain
oil
An oil is any nonpolar chemical substance that is composed primarily of hydrocarbons and is hydrophobic (does not mix with water) & lipophilic (mixes with other oils). Oils are usually flammable and surface active. Most oils are unsaturate ...
s, 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 liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it ...
.
The ACADM gene is located on the short (p) arm of
chromosome 1
Chromosome 1 is the designation for the largest human chromosome. Humans have two copies of chromosome 1, as they do with all of the autosomes, which are the non- sex chromosomes. Chromosome 1 spans about 249 million nucleotide base pairs, whi ...
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.
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. 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. Furthermore, MCAD participates in fatty acid metabolism and PPAR signaling pathway.
Clinical significance
Medium-chain acyl-coenzyme A dehydrogenase deficiency
Medium-chain acyl-CoA dehydrogenase deficiency (MCAD deficiency or MCADD) is a disorder of fatty acid oxidation that impairs the body's ability to break down medium-chain fatty acids into acetyl-CoA. The disorder is characterized by hypoglycemia ...
can be caused by
mutation
In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, m ...
s in the ACADM gene. More than 54 ACADM gene mutations that cause medium-chain acyl-coenzyme A dehydrogenase deficiency have been identified. Many of these mutations switch an amino acid building block in the ACADM enzyme. The most common
amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha ...
substitution
Substitution may refer to:
Arts and media
*Chord substitution, in music, swapping one chord for a related one within a chord progression
*Substitution (poetry), a variation in poetic scansion
* "Substitution" (song), a 2009 song by Silversun Pic ...
replaces
lysine
Lysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. It contains an α-amino group (which is in the protonated form under biological conditions), an α-carboxylic acid group (which is in the deprotonated &minu ...
with
glutamic acid
Glutamic acid (symbol Glu or E; the ionic form is known as glutamate) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can syn ...
at position 329 in the enzyme's chain of amino acids (also written as Lys329Glu or K329E). 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.
References
Further reading
*
*
External links
GeneReviews/NIH/NCBI/UW entry on Medium-Chain Acyl-Coenzyme A Dehydrogenase DeficiencyGeneCardACADM at The GDB Human Genome Database
*
{{Lipid metabolism enzymes