BCKDK
BCKDK (branched chain keto acid dehydrogenase kinase) is a mitochondrial serine/threonine-protein kinase that phosphorylates and inactivates the branched-chain alpha-ketoacid dehydrogenase complex. It acts as a regulatory node linking branched-chain amino acid, glucose and lipid metabolism. Browse Assay Genie's current range of BCKDK research reagents below, or read on for the biology behind the target.
BCKDK is a serine/threonine-protein kinase and a component of macronutrient metabolism. It forms a functional kinase and phosphatase pair with PPM1K, and together they act as a metabolic regulatory node that coordinates branched-chain amino acids (BCAAs) with glucose and lipid metabolism. This is done through two distinct phosphoprotein targets: the mitochondrial BCKDHA subunit of the branched-chain alpha-ketoacid dehydrogenase (BCKDH) complex, and the cytosolic ACLY, a lipogenic enzyme of the Krebs cycle.
The BCKDH complex is a multisubunit assembly with three multimeric components, each involved in a different step of BCAA catabolism: E1 (BCKDHA and BCKDHB), an E2 core of DBT monomers, and E3 (DLD monomers). BCKDK associates with the E2 component and phosphorylates BCKDHA on Ser-337. This causes conformational changes that interrupt substrate channelling between E1 and E2 and so inactivates the complex. NCBI describes the complex as an important regulator of the valine, leucine and isoleucine catabolic pathways. BCKDK recognises phosphosites with a canonical SxxE/D motif.
BCKDK also phosphorylates ACLY on Ser-455 in response to changes in cellular carbohydrate abundance, as occurs in the fasting to feeding transition. Refeeding stimulates the transcription factor MLXIPL/ChREBP, raising the BCKDK to PPM1K expression ratio. This increases ACLY phosphorylation and activation, which generates malonyl-CoA and oxaloacetate, the immediate substrates of de novo lipogenesis and glucogenesis. The BCKDK gene belongs to the PDK/BCKDK protein kinase family, and several transcript variants encoding different isoforms have been reported. Mouse and rat both have a Bckdk ortholog.
BCKDK phosphorylates and inactivates the BCKDH complex, making it a key control point in valine, leucine and isoleucine breakdown.
By phosphorylating ACLY, BCKDK links carbohydrate availability to production of malonyl-CoA and oxaloacetate, substrates of de novo lipogenesis and glucogenesis.
The BCKDK to PPM1K expression ratio rises on refeeding under MLXIPL/ChREBP control, a useful readout of nutrient-state signalling.
As a PDK/BCKDK family member in the mitochondrial matrix, BCKDK offers a model for kinase-phosphatase regulation of metabolic complexes.
BCKDK is a mitochondrial serine/threonine kinase that phosphorylates BCKDHA on Ser-337, inactivating the BCKDH complex and halting BCAA catabolism. It also phosphorylates ACLY on Ser-455, linking branched-chain amino acid handling to glucose and lipid metabolism. PPM1K acts as its partner phosphatase.
BCKDK stands for branched chain keto acid dehydrogenase kinase; UniProt lists it as branched-chain alpha-ketoacid dehydrogenase kinase. HGNC records no alternative aliases or previous symbols. NCBI notes that several transcript variants encoding different isoforms have been found for this gene.
Mouse and rat both carry a Bckdk ortholog, so the kinase can be studied in common rodent models. In humans it belongs to the PDK/BCKDK protein kinase family. Check the datasheet of any product for its validated reactivity.
BCKDH complex subunits, the partner phosphatase PPM1K and lipogenic pathway proteins connected to BCKDK.
Gene and protein annotations from HGNC, NCBI Gene and UniProt O14874; product specifications from Assay Genie datasheets.