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Disruption of genes encoding pyruvate dehydrogenase kinases leads to retarded growth on acetate and ethanol in Saccharomyces cerevisiae
Author(s) -
Yde Steensma H.,
Tomaska Lubomir,
Reuven Peter,
Nosek Jozef,
Brandt Raymond
Publication year - 2008
Publication title -
yeast
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.923
H-Index - 102
eISSN - 1097-0061
pISSN - 0749-503X
DOI - 10.1002/yea.1543
Subject(s) - pyruvate dehydrogenase phosphatase , biology , pyruvate dehydrogenase kinase , pyruvate dehydrogenase complex , biochemistry , pyruvate kinase , mutant , phosphoenolpyruvate carboxykinase , oxoglutarate dehydrogenase complex , acetate kinase , pyruvate decarboxylation , alcohol dehydrogenase , branched chain alpha keto acid dehydrogenase complex , dehydrogenase , wild type , gene , microbiology and biotechnology , enzyme , glycolysis , escherichia coli
Two open reading frames, YIL042c ( PKP1 ) and YGL059w, with 25% sequence similarity to human pyruvate dehydrogenase kinases, were shown to have protein kinase activity. Using GFP fusions, it was demonstrated that the proteins localize in discrete submitochondrial regions. Strains with a null mutation in these loci grew poorly on acetate and ethanol as carbon sources. Doubling times increased from ca. 4 h in the wild‐type to > 6 h for the mutants. Growth rates of the mutants could be restored to wild‐type levels by simultaneous disruption of the PDA1 gene, encoding the E1α subunit of the pyruvate dehydrogenase complex. This observation and the pyruvate dehydrogenase activities measured in the mutant strains and the wild‐type grown on glucose or acetate suggest that the slow growth phenotype on C2 carbon sources is caused by a futile cycle in which phosphoenolpyruvate is converted back to acetyl coenzyme A. Copyright © 2007 John Wiley & Sons, Ltd.