HADHB

Trifunctional enzyme subunit beta, mitochondrial (TP-beta) also known as 3-ketoacyl-CoA thiolase, acetyl-CoA acyltransferase, or beta-ketothiolase is an is_associated_with::enzyme that in humans is encoded by the HADHB is_associated_with::gene.

HADHB is a subunit of the is_associated_with::mitochondrial trifunctional protein and has is_associated_with::thiolase activity.

Structure
The HADHB gene is located on chromosome 2, with its specific location being 2p23. The gene contains 17 exons. HADHB encodes a 51.2 kDa protein hat is composed of 474 is_associated_with::amino acids; 124 is_associated_with::peptides have been observed through is_associated_with::mass spectrometry data.

Function
This gene encodes the beta subunit of the mitochondrial trifunctional protein, a catalyst of mitochondrial is_associated_with::beta-oxidation of long chain fatty acids. The HADHB protein catalyzes the final step of beta-oxidation, in which 3-ketoacyl CoA is cleaved by the is_associated_with::thiol group of another molecule of is_associated_with::Coenzyme A. The thiol is inserted between C-2 and C-3, which yields an is_associated_with::acetyl CoA molecule and an is_associated_with::acyl CoA molecule, which is two carbons shorter.

The encoded protein can also bind is_associated_with::RNA and decreases the stability of some is_associated_with::mRNAs. The genes of the alpha and beta subunits of the mitochondrial trifunctional protein are located adjacent to each other in the is_associated_with::human genome in a head-to-head orientation.

Clinical significance
Mutations in this gene, along with mutations in is_associated_with::HADHA, result in is_associated_with::trifunctional protein deficiency. Mutations in either gene have similar clinical presentations. Trifunctional protein deficiency is characterized by decreased activity of long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD), long-chain enoyl-CoA hydratase, and long-chain thiolase. This deficiency can be classified into 3 main clinical phenotypes: is_associated_with::neonatal onset of a severe, lethal condition resulting in is_associated_with::sudden infant death syndrome (SIDS), infantile onset of a hepatic Reye-like syndrome, and late-adolescent onset of primarily a skeletal is_associated_with::myopathy. Additionally, some presents showed symptoms associated with myopathy, recurrent and episodic is_associated_with::rhabdomyolysis, and sensorimotor axonal is_associated_with::neuropathy. In some cases, symptoms of the deficiency can present as dilated is_associated_with::cardiomyopathy, congestive is_associated_with::heart failure, and respiratory failure. The deficiency has presented as hydrops fetalis and HELLP syndrome in fetuses. A compound heterozygous mutation of the HADHB gene can causes axonal is_associated_with::Charcot-Marie-tooth disease, which is a neurological disorder, which shows that mutations in this gene can result in deficiencies that present in new forms not currently described.

Interactions
HADHB is a functional molecular target of ERα in the mitochondria, and the interaction may play an important role in the is_associated_with::estrogen-mediated is_associated_with::lipid metabolism in animals and humans. Additionally, HADHB has been shown to bind to the distal 3’ untranslated region of renin mRNA, thereby regulating renin protein expression.