HADHB Gene

The official name of HADHB gene is hydroxyacyl-Coenzyme A dehydrogenase/3-ketoacyl-Coenzyme. The HADHB gene provides instructions for making part of an enzyme complex called mitochondrial trifunctional protein. This enzyme complex functions in mitochondria, the energy-producing centers within cells. It is found in the mitochondrimitochondrial trifunctional proteina of several tissues, particularly the heart, liver, muscles, and the part of the eye that detects light and color (the retina).Mitochondrial trifunctional protein is required to break down (metabolize) a group of fats called long-chain fatty acids. Long-chain fatty acids are found in foods such as milk and certain oils, and they are also stored in the body's fat tissues. Mitochondrial trifunctional protein is essential for converting long-chain fatty acids to the major source of energy used by the heart and muscles. During periods without food (fasting), this energy source is also important for the liver and other tissues.

Function:

As the name suggests, mitochondrial trifunctional protein performs three functions. It has three enzyme activities that are essential for fatty acid oxidation, which is the multistep process that metabolizes fats and converts them to energy. The beta subunit performs one of the enzyme activities, known as long-chain 3-keto-acyl-coenzyme A thiolase. The alpha subunit carries out the other two enzyme activities.

Location:

HADHA gene is present in human chromosome 2 and its coded from region 26321120 to 26366837 base pairs with 20 exons, the cytogenetic location 2p23.

Disease

Mutations in this gene causes mitochondrial trifunctional protein deficiency.

In mitochondrial trifunctional protein deficiency Researchers have identified at least 20 HADHB gene mutations that reduce all three enzyme activities of mitochondrial trifunctional protein. Most mutations change one of the building blocks (amino acids) used to make the protein's beta subunit. A change in amino acids probably alters the subunit's structure, which disrupts all three activities of the enzyme complex. Some mutations produce abnormally small, unstable beta subunits, which leads to a decreased amount of mitochondrial trifunctional protein. With a loss of mitochondrial trifunctional protein activity, long-chain fatty acids cannot be metabolized and processed. As a result, these fatty acids are not converted to energy, which can lead to the characteristic features of this disorder, such as lethargy and low blood sugar. Long-chain fatty acids or partially metabolized fatty acids may build up in tissues and damage the liver, heart, and muscles, causing more serious complications.