BCKDK phosphorylates BCKDH

Stable Identifier
Reaction [transition]
Homo sapiens
Locations in the PathwayBrowser
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

Mitochondrial 3-methyl-2-oxobutanoate dehydrogenase (lipoamide) kinase (BCKDK) catalyses the phosphorylation and inactivation of the branched-chain alpha-ketoacid dehydrogenase (BCKDH) complex, the key regulatory enzyme of the valine, leucine and isoleucine catabolic pathways (Li et al. 2004, Wynn et al. 2004). BCKDH occupies a strategic point in the branched-chain amino acid (BCAA) catabolic pathway, and careful regulation of its activity is essential for correct BCAA metabolism. The overall activity of the BCKDH complex is controlled by the phosphorylation (inactivation)/dephosphorylation (activation) cycle.
Defects in BCKDK can cause branched-chain ketoacid dehydrogenase kinase deficiency (BCKDKD; MIM:614923), a metabolic disorder characterised by autism, epilepsy, intellectual disability, and reduced BCAAs (Novarino et al. 2012, Garcia-Cazorla et al. 2014).

Literature References
PubMed ID Title Journal Year
24449431 Two novel mutations in the BCKDK (branched-chain keto-acid dehydrogenase kinase) gene are responsible for a neurobehavioral deficit in two pediatric unrelated patients

Garcia-Cazorla, A, Oyarzabal, A, Fort, J, Robles, C, Castejón, E, Ruiz-Sala, P, Bodoy, S, Merinero, B, Lopez-Sala, A, Dopazo, J, Nunes, V, Ugarte, M, Artuch, R, Palacin, M, Rodríguez-Pombo, P, Alcaide, P, Navarrete, R, Sanz, P, Font-Llitjós, M, Vilaseca, MA, Ormaizabal, A, Pristoupilova, A, Agulló, SB

Hum. Mutat. 2014
15166214 Cross-talk between thiamin diphosphate binding and phosphorylation loop conformation in human branched-chain alpha-keto acid decarboxylase/dehydrogenase

Li, J, Wynn, RM, Machius, M, Chuang, JL, Karthikeyan, S, Tomchick, DR, Chuang, DT

J. Biol. Chem. 2004
15576032 Molecular mechanism for regulation of the human mitochondrial branched-chain alpha-ketoacid dehydrogenase complex by phosphorylation

Wynn, RM, Kato, M, Machius, M, Chuang, JL, Li, J, Tomchick, DR, Chuang, DT

Structure 2004
22956686 Mutations in BCKD-kinase lead to a potentially treatable form of autism with epilepsy

Novarino, G, El-Fishawy, P, Kayserili, H, Meguid, NA, Scott, EM, Schroth, J, Silhavy, JL, Kara, M, Khalil, RO, Ben-Omran, T, Ercan-Sencicek, AG, Hashish, AF, Sanders, SJ, Gupta, AR, Hashem, HS, Matern, D, Gabriel, S, Sweetman, L, Rahimi, Y, Harris, RA, State, MW, Gleeson, JG

Science 2012
Participant Of
Event Information
Catalyst Activity
Catalyst Activity
[3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)] kinase activity of BCKDK [mitochondrial matrix]
Physical Entity
Orthologous Events
Cite Us!