Pathway
Branched-chain ketoacid dehydrogenase kinase deficiency
Branched-chain ketoacid dehydrogenase kinase deficiency (BCKDKD) is a neurological disorder that arises due to mutations in branched-chain ketoacid dehydrogenase kinase (BCKDK). BCKDK is a negative regulator of the branched-chain ketoacid dehydrogenase complex (BCKDH), the enzyme responsible for oxidative decarboxylation of branched-chain amino acid derivatives. BCKDK-dependent phosphorylation of serine residues in the E1 alpha subunit of the enzyme BCKDHA inactivates the BCKDH.
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Inactivating mutations of BCKDK are associated with impaired intellectual development, microencephaly and autism. Consistent with the role of BCKDK in inhibiting BCKDH activity, inactivating mutations in BCKDK result in higher levels of BCKDH activity and reduced BCAAs in plasma, tissues and urine in mouse models, patients and cell lines. Symptoms of BCKDK deficiency are alleviated in mouse models by dietary supplementation with a BCAA-enriched diet.
What the reference databases state
Statements
5 statements
5 statements · 1 reference database · Subject: Branched-chain ketoacid dehydrogenase kinase deficiency · Sources: Reactome
- BCKDHA participates in Branched-chain ketoacid dehydrogenase kinase deficiencyProteinReactome R-HSA-9912481Inferred only
- BCKDHB participates in Branched-chain ketoacid dehydrogenase kinase deficiencyProteinReactome R-HSA-9912481Inferred only
- BCKDK participates in Branched-chain ketoacid dehydrogenase kinase deficiencyProteinReactome R-HSA-9912481Inferred only
- DBT participates in Branched-chain ketoacid dehydrogenase kinase deficiencyProteinReactome R-HSA-9912481Inferred only
- DLD participates in Branched-chain ketoacid dehydrogenase kinase deficiencyProteinReactome R-HSA-9912481Inferred only