ACADM

ACADM (acyl-Coenzyme A dehydrogenase, C-4 to C-12 straight chain) is a is_associated_with::gene that provides instructions for making an enzyme called is_associated_with::acyl-coenzyme A dehydrogenase that is important for breaking down (degrading) a certain group of fats called is_associated_with::medium-chain fatty acids.

These is_associated_with::fatty acids are found in foods such as is_associated_with::milk and certain is_associated_with::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 is_associated_with::mitochondria of several types of tissues, particularly the is_associated_with::liver.

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

Structure
The protein encoded by the ACADM gene is 50.8 kDa in size, and composed of 454 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. LCAD 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.

Clinical significance
is_associated_with::Medium-chain acyl-coenzyme A dehydrogenase deficiency can be caused by is_associated_with::mutations in the ACADM gene. More than 30 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 is_associated_with::amino acid substitution replaces is_associated_with::lysine with is_associated_with::glutamic acid 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.