Reactome | BCKDK phosphorylates BCKDH

BCKDK phosphorylates BCKDH

Stable Identifier

R-HSA-5693148

Type

Reaction [transition]

Species

Homo sapiens

Compartment

mitochondrial matrix

Synonyms

ATP + L-seryl-(3-methyl-2-oxobutanoate dehydrogenase) => ADP + H(+) + O-phospho-L-seryl-(3-methyl-2-oxobutanoate dehydrogenase)

ReviewStatus

5/5

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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
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
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
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