Hydroxyacyl-Coenzyme A dehydrogenase

Hydroxyacyl-Coenzyme A dehydrogenase also known as HADH is an is_associated_with::enzyme which in humans is encoded by the HADH is_associated_with::gene.

Structure
The HADH gene is located on the 4th chromosome, with its specific location being identified as 4q22-q26. The gene has 10 is_associated_with::exons. The HADH gene encodes a 34.3 kDa protein that has 314 amino acids and 124 observed is_associated_with::peptides.

Function
This gene is a member of the is_associated_with::3-hydroxyacyl-CoA dehydrogenase gene family. The encoded protein functions in the is_associated_with::mitochondrial matrix to catalyze the oxidation of straight-chain 3-hydroxyacyl-CoAs as part of the is_associated_with::beta-oxidation pathway. Its enzymatic activity is highest with medium-chain-length fatty acids.

Clinical significance
Mutations in this gene cause one form of familial is_associated_with::hyperinsulinemic hypoglycemia. A deficiency is associated with is_associated_with::3-hydroxyacyl-coenzyme A dehydrogenase deficiency. Mutations also cause 3-hydroxyacyl-CoA dehydrogenase deficiency. There are a wide variety of mutations that have been identified to cause this disease. Among them are missense mutations (A40T, P258L, D57G, Y226H) and  nonsense mutations (R236X) in the protein, and is_associated_with::splicing mutations (261+1G>A, 710-2A>G) and some small deletions (587delC) in the is_associated_with::cDNA. One mutation, 636+471G>T in the HADH gene, was shown to create a cryptic splice donor site and an out-of-frame is_associated_with::pseudoexon. Most of the described cases have homozygous mutations. This disease has fairly homogenous clinical presentation across cases. The symptoms first appear in early life, between 1.5 hours post birth and 3 years of age, and the most common symptoms are is_associated_with::hypoglycemia and seizures/convulsions directly related to the hypoglycemia. There are other clinical presentations that have been identified, namely: is_associated_with::myoglobinuria, is_associated_with::dicarboxylic aciduria, feeding difficulties in infancy, muscular is_associated_with::hypotonia, hepatic is_associated_with::steatosis, growth delay, hypertrophic is_associated_with::cardiomyopathy, dilated cardiomyopathy, hepatic is_associated_with::necrosis, and fulminant hepatic failure. The disorder may be diagnosed by either the analysis of the is_associated_with::molecular genetics of the individual, or by detection of abnormal metabolite levels in blood and/or plasma. Individuals with this deficiency have an elevated amount of 3-hydroxyglutarate excreted through the urine; a heightened level of C4-OH acylcarnitine in the blood plasma is also a characteristic of this FAO disorder. Most documented cases thus far have shown that individuals are responsive to is_associated_with::diazoxide treatment, and highlight the need for diagnosis and treatment administration as early as possible in order to correct hypoglycemia and avoid irreversible is_associated_with::brain damage.

Interactions
HADH has been shown to interact with is_associated_with::Vpr, such that HIV-1 Vpr regulates mitochondrial respiration and enhances the activity of hydroxyacyl-CoA dehydrogenase (HADH) through PPARbeta/delta.