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H139Hfs13* PPM1K causes a mild variant of MSUD

Summary

Organism

Homo sapiens (human)

Reactome

R-HSA-9912529

PubChem

R-HSA-9912529

Description

PPM1K is a mitochondrial protein phosphatase that removes the inhibitory phosphorylation from the E1 beta subunit of branched-chain ketoacid dehydrogenase (BCKDH) to restore BCKDH activity (Lu et al, 2007; Lu et al, 2009 a, b; Wynn et al, 2012; Zhou et al, 2012).
BCKDH is responsible for the oxidative decarboxylation of branched-chain amino acid (BCAA) derivatives of leucine, valine and isoleucine, providing acetyl CoA and succinyl CoA intermediates for the Krebs Cycle (reviewed in Strauss et al, 2020; Zhang et al, 2023). Loss-of-function mutations in subunits of BCKDH cause accumulation of toxic BCAAs in the urine, neurological defects and are the cause of Maple Syrup Urine disease (MSUD). More recently, a frameshift mutation in PPM1K was identified as the probable cause of a mild variant of MSUD (Oyarzabal et al, 2012). This frameshift introduces a stop codon at residue 151, destabilizing the protein, and transfection of PPM1K-deficient fibroblast lines with WT PPM1K restores BCKDH activity (Oyarzabal et al, 2012).

Click on a node on the pathway to see its details. Glycoproteins are marked with a glycoprotein icon in their name.

SPV: a JavaScript Signaling Pathway Visualizer, Bioinformatics, 2018

Displaying 1 entry
UniProt ID	Protein Name	Gene Symbol	Pathway Viewer
P09622	Dihydrolipoyl dehydrogenase, mitochondrial	DLD GCSL LAD PHE3	view

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