Disease relevance of BCKDK

• Thus two catabolic signals associated with renal failure, GC and acidification, reduce BCKD kinase expression by different mechanisms [1].

High impact information on BCKDK

• ThDP binding that orders the loop prevents phosphorylation of E1b by the BCKD kinase and averts the inactivation of wild-type E1b, but not the above mutants, by this covalent modification [2].
• A cDNA for branched-chain alpha-ketoacid dehydrogenase kinase was cloned from a rat heart cDNA library [3].
• Branched-chain alpha-ketoacid dehydrogenase kinase. Molecular cloning, expression, and sequence similarity with histidine protein kinases [3].
• To design the primers for the polymerase chain reaction, human BCKDK was cloned [4].
• Dexamethasone, a synthetic GC, decreased BCKD kinase protein by 65% (P < 0.05 vs. control), whereas a low pH (i.e., pH 7.0) decreased the amount of kinase by 71% (P < 0.05 vs. control) [1].

Biological context of BCKDK

• Arg288 is required for recognition by BCKDK of the phosphorylation site on the E1alpha subunit of the BCKDH complex [5].
• BCKDK inhibits the dehydrogenase activity of the BCKDH complex by introducing a negative charge into the active-site pocket of the E1 component [5].

Anatomical context of BCKDK

• Here we show that elimination of the branched-chain amino acids from the medium of cultured cells results in a two- to threefold increased production of the branched-chain alpha-ketoacid dehydrogenase kinase with a decrease in the activity state of the branched-chain alpha-ketoacid dehydrogenase complex [6].
• A method has been developed for the activation of the branched-chain alpha-ketoacid dehydrogenase complex by alpha-chloroisocaproate, an inhibitor of branched-chain alpha-ketoacid dehydrogenase kinase in human cultured skin fibroblasts [7].

Associations of BCKDK with chemical compounds

• To investigate this possibility, we examined how dexamethasone and acidification (pH 7.0) influence BCKD kinase expression in LLC-PK(1)-GR101 cells [1].
• These include pyruvate dyhydrogenase kinase, branched-chain alpha-ketoacid dehydrogenase kinase, protein kinase A, protein kinase Cdelta, stress-activated kinase and A-Raf as well as unidentified kinases [8].

Analytical, diagnostic and therapeutic context of BCKDK

• Northern blot analysis indicated the mRNA for the branched-chain alpha-ketoacid dehydrogenase kinase was more abundant in rat heart than in rat liver, as expected from the relative amounts of kinase activity expressed in these tissues [3].

References