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Brain pyruvate and 2‐oxoglutarate dehydrogenase complexes are mitochondrial targets of the CoA ester of the Refsum disease marker phytanic acid
Author(s) -
Bunik Victoria I.,
Raddatz Günter,
Wanders Ronald J.A.,
Reiser Georg
Publication year - 2006
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2006.05.040
Subject(s) - phytanic acid , biochemistry , pyruvate dehydrogenase complex , dehydrogenase , oxoglutarate dehydrogenase complex , chemistry , branched chain alpha keto acid dehydrogenase complex , palmitic acid , enzyme , peroxisome , fatty acid , gene
Pyruvate and 2‐oxoglutarate dehydrogenase complexes are strongly inhibited by phytanoyl‐CoA (IC 50 ≈ 10 −6 –10 −7 M). Palmitoyl‐CoA is 10‐fold less potent. Phytanic or palmitic acids have no inhibitory effect up to 0.3 mM. At the substrate saturation, the acyl‐CoA's affect the first and second enzymatic components of the 2‐oxoglutarate dehydrogenase complex, while the third component is inhibited only at a low saturation with its substrate dihydrolipoamide. Thus, key regulatory branch points of mitochondrial metabolism are targets of a cellular derivative of phytanic acid. Decreased activity of the complexes might therefore contribute to neurological symptoms upon accumulation of phytanic acid in Refsum disease.