bckd-1A Antibody

Structure and Function of the BCKDHA Protein

The BCKDHA protein forms part of the E1 component (α₂β₂ heterotetramer) of the BCKD complex, which includes:

• E1 (BCKDHA/BCKDHB): Catalyzes α-ketoacid decarboxylation.

• E2 (DBT): Contains lipoic acid and facilitates acyl transfer.

• E3 (DLD): Oxidizes dihydrolipoamide to regenerate lipoic acid.

BCKDHA interacts with the E1β subunit (BCKDHB) to form the E1 component, which binds thiamine pyrophosphate (TPP) as a cofactor .

Applications of the BCKDHA Antibody

The BCKDHA antibody is utilized in diverse research and diagnostic methods:

Role in Maple Syrup Urine Disease (MSUD)

Mutations in BCKDHA (e.g., Tyr438Asn) disrupt BCKD function, leading to BCAA accumulation. Antibodies like ab126173 (Abcam) validate BCKDHA knockout models, showing absent E1α signals in Western blots .

Regulation by PP2Cm and BCKA Substrates

• PP2Cm: A mitochondrial phosphatase that dephosphorylates E1α (Ser293), activating BCKD. BCKDHA antibodies confirm PP2Cm-mediated dephosphorylation in response to BCKA substrates .

• BCKA Substrates: BCKDHA antibodies demonstrate rapid dissociation of BCKD kinase (BCKDK) from the BCKD complex under high BCKA conditions, enabling enzyme activation .

Tumor Metabolism and Immunomodulation

In glioblastoma (GBM), BCKA metabolites (e.g., α-ketoisovalerate) are transported via MCT1 into tumor-associated macrophages, reducing phagocytic activity. BCKDHA antibodies may aid in studying BCKD expression in GBM .

Phosphorylation-Dependent Regulation

BCKD is regulated by BCKDK (kinase) and PP2Cm (phosphatase). BCKDHA antibodies reveal that BCKA substrates rapidly dissociate BCKDK from the complex, while PP2Cm persists, enabling sustained dephosphorylation .