3-hydroxyacyl-CoA dehydrogenase deficiency At least three mutations in the HADH gene have been found to cause 3-hydroxyacyl-CoA dehydrogenase deficiency. These mutations change single protein building blocks (amino acids) used to make the 3-hydroxyacyl-CoA dehydrogenase enzyme. These changes probably alter the 3-dimensional shape of the enzyme, which impairs its normal function. With a shortage (deficiency) of functional 3-hydroxyacyl-CoA dehydrogenase, medium-chain and short-chain fatty acids are not metabolized properly. As a result, these fatty acids are not converted to energy, which can lead to signs and symptoms of 3-hydroxyacyl-CoA dehydrogenase deficiency such as lack of energy (lethargy) and low blood sugar (hypoglycemia). Medium-chain and short-chain fatty acids that are not broken down can build up in tissues and damage the liver, heart, and muscles, causing serious complications. congenital hyperinsulinism Genetics Home Reference provides information about congenital hyperinsulinism. other disorders Mutations in the HADH gene have been reported in a small number of people with familial hyperinsulinism. This disorder is characterized by abnormally high levels of insulin (hyperinsulinism) and unusually low blood sugar (hypoglycemia). Researchers have identified at least five HADH gene mutations that cause familial hyperinsulinism. These mutations severely reduce 3-hydroxyacyl-CoA dehydrogenase activity, either by impairing the enzyme's function or by decreasing the amount of this enzyme in cells. Researchers believe that inadequate 3-hydroxyacyl-CoA dehydrogenase activity in the pancreas leads to excessive insulin secretion and hypoglycemia in people with familial hyperinsulinism. It is unclear why the HADH gene mutations that cause familial hyperinsulinism seem to affect only the pancreas.

     The HADH gene provides instructions for making an enzyme called 3-hydroxyacyl-CoA dehydrogenase that is important for converting certain fats to energy. This enzyme is involved in a process called fatty acid oxidation, in which several enzymes work in a step-wise fashion to break down (metabolize) fats and convert them to energy. The role of 3-hydroxyacyl-CoA dehydrogenase is to metabolize groups of fats called medium-chain fatty acids and short-chain fatty acids. These fatty acids are found in foods such as milk and certain oils and are produced when larger fatty acids are metabolized. 3-hydroxyacyl-CoA dehydrogenase functions in mitochondria, the energy-producing centers within cells. This enzyme is especially important for the normal functioning of the heart, liver, kidneys, muscles, and pancreas. The pancreas makes enzymes that help digest food, and it also produces insulin, which controls how much sugar is passed from the blood into cells for conversion to energy. 3-hydroxyacyl-CoA dehydrogenase is essential in the process that converts medium-chain and short-chain fatty acids to ketones, the major source of energy used by the heart and muscles. During prolonged periods without food (fasting) or when energy demands are increased, ketones are also important for the liver and other tissues.

The following transcription factors affect gene expression:

• PPAR-gamma1
• HNF-1A
• PPAR-gamma2
• HNF-1
• C/EBPalpha
• HNF-4alpha1
• HNF-4alpha2

Tissue specificity:

Expressed in liver, kidney, pancreas, heart and skeletal muscle.

Molecular Function:

• 3-Hydroxyacyl-Coa Dehydrogenase Activity
• Acetyl-Coa C-Acetyltransferase Activity
• Enoyl-Coa Hydratase Activity
• Fatty-Acyl-Coa Binding
• Long-Chain-3-Hydroxyacyl-Coa Dehydrogenase Activity
• Long-Chain-Enoyl-Coa Hydratase Activity
• Nad Binding
• Nad+ Binding

Biological Processes:

• Cardiolipin Acyl-Chain Remodeling
• Fatty Acid Beta-Oxidation
• Response To Insulin
• Negative Regulation Of Insulin Secretion