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Target intelligence / Profile preview
Branched-chain α-keto acid dehydrogenase kinase (BCKDK)
- Target
- BCKDK
- Molecular classification
- Enzyme, Protein kinase
01
Overview
Branched-chain α-keto acid dehydrogenase kinase (BCKDK) is a mitochondrial protein kinase that regulates the activity of the branched-chain α-keto acid dehydrogenase complex (BCKDH) by phosphorylating and inactivating it. This regulation is essential for the maintenance of branched-chain amino acid (BCAA: leucine, isoleucine, valine) homeostasis. Mutations or abnormal activity of BCKDK contribute to metabolic diseases due to impaired BCAA catabolism. BCKDK itself is a therapeutic target in multiple metabolic disorders, and its activity can be modulated by small-molecule allosteric inhibitors that lower BCAA levels and reactivate BCKDH.
- Other names
- Branched-chain ketoacid dehydrogenase kinaseBCKD kinaseBDKBCKDK
02
Mechanism of action
Inhibitors of BCKDK prevent the phosphorylation and inactivation of the BCKDH complex, thereby increasing catabolism of branched-chain amino acids
03
Biological functions
Regulation of branched-chain amino acid catabolismMaintenance of branched-chain amino acid homeostasisInhibition of the branched-chain α-keto acid dehydrogenase complex
04
Disease associations
Metabolic disease (e.g., maple syrup urine disease)Heart failureObesityType 2 diabetes
05
Safety considerations
Risk of excessive BCAA catabolism leading to hypoglycemia or metabolic imbalancePotential neurological effects if BCAA levels become too low, as BCAAs are critical for brain function
06
Interacting drugs
(S)-α-chlorophenylpropionic acid [(S)-CPP]
3 more in the full profile.
07
Biomarkers
Plasma branched-chain amino acid levelsPhosphorylation state of BCKDH E1α subunit
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