BCKDHA Human
Description
Product Specs
Product Science Overview
Branched Chain Keto Acid Dehydrogenase E1 Alpha (BCKDHA) is a crucial enzyme subunit involved in the catabolism of branched-chain amino acids (BCAAs) such as leucine, isoleucine, and valine. These amino acids are essential nutrients obtained from dietary sources like milk, meat, and eggs. The BCKDHA gene provides instructions for producing the alpha subunit of the branched-chain alpha-keto acid dehydrogenase (BCKD) enzyme complex .
The BCKD enzyme complex is a multi-subunit complex located on the mitochondrial inner membrane. It catalyzes the oxidative decarboxylation of branched, short-chain alpha-keto acids, which is an irreversible step in the catabolism of BCAAs . The BCKD complex consists of three catalytic components:
- E1: Alpha-ketoacid dehydrogenase (BCKDHA) with thiamine pyrophosphate (TPP) as a cofactor.
- E2: Dihydrolipoyl transacylase (DBT) with lipoic acid and coenzyme A as cofactors.
- E3: Dihydrolipoamide dehydrogenase (DLD) with FAD and NAD as cofactors .
In humans, the E1 component is composed of two alpha subunits (produced by the BCKDHA gene) and two beta subunits (produced by the BCKDHB gene), forming a tetramer . The E2 component forms the core of the complex, with 24 copies arranged in octahedral symmetry .
The BCKD enzyme complex plays a vital role in energy production by breaking down BCAAs into molecules that can be used for energy. This process occurs in the mitochondria, the energy-producing centers of cells . The breakdown of leucine, isoleucine, and valine produces α-Methylbutyryl-CoA, Isobutyryl-CoA, and Isovaleryl-CoA, respectively .
Mutations in the BCKDHA gene can lead to a metabolic disorder known as Maple Syrup Urine Disease (MSUD). This condition is characterized by the accumulation of BCAAs and their byproducts in the body, which can be toxic to cells and tissues, particularly in the nervous system . Symptoms of MSUD include poor feeding, vomiting, lethargy, abnormal movements, and delayed development. The disease gets its name from the distinctive sweet odor of affected infants’ urine .
Human recombinant BCKDHA is produced using recombinant DNA technology, which involves inserting the BCKDHA gene into a suitable expression system, such as bacteria or yeast, to produce the protein in large quantities. This recombinant protein can be used for research purposes, including studying the enzyme’s structure, function, and role in metabolic disorders.
