Regulation of branched-chain amino acid catabolism via BCKDK and PPM1K

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Contributors

Alexander Mazein1

Affiliations
  1. 1Department of Cancer Research, Luxembourg Institute of Health, Strassen, Luxembourg

Reactome-Recon connection

The connection was chosen from the Reactome-Recon lists: proteins of the Recon2 metabolic reconstruction that take part in Reactome signalling processes. The BCKDH complex is in the lists through the Reactome processes BCKDK phosphorylates BCKDH (R-HSA-5693148) and PPM1K dephosphorylates p-BCKDH (R-HSA-5693153).

Description

The branched-chain amino acids leucine, isoleucine and valine share the first two steps of their breakdown in mitochondria: BCAT2 transfers their amino group to α-ketoglutarate, and the branched-chain α-keto acid dehydrogenase complex (BCKDH) converts the resulting keto acids to their acyl-CoA esters, the rate-limiting step. The kinase BCKDK inactivates BCKDH by phosphorylation and the phosphatase PPM1K reactivates it. The keto acids, above all α-ketoisocaproate from leucine, inhibit BCKDK, so an excess of branched-chain amino acids speeds up their own breakdown.

References

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