Showing papers by "Bas Teusink published in 2001"
TL;DR: It is demonstrated how the intracellular concentrations of metabolites can reveal phenotypes for proteins active in metabolic regulation, and this approach to functional analysis, using comparative metabolomics, is called FANCY—an abbreviation for functional analysis by co-responses in yeast.
Abstract: A large proportion of the 6,000 genes present in the genome of Saccharomyces cerevisiae, and of those sequenced in other organisms, encode proteins of unknown function. Many of these genes are "silent," that is, they show no overt phenotype, in terms of growth rate or other fluxes, when they are deleted from the genome. We demonstrate how the intracellular concentrations of metabolites can reveal phenotypes for proteins active in metabolic regulation. Quantification of the change of several metabolite concentrations relative to the concentration change of one selected metabolite can reveal the site of action, in the metabolic network, of a silent gene. In the same way, comprehensive analyses of metabolite concentrations in mutants, providing "metabolic snapshots," can reveal functions when snapshots from strains deleted for unstudied genes are compared to those deleted for known genes. This approach to functional analysis, using comparative metabolomics, we call FANCY—an abbreviation for functional analysis by co-responses in yeast.
1,014 citations
TL;DR: It is shown that yeast sugar transport has substantial but not complete control of the frequency of glycolytic oscillations, and most but not all control resides in glucose transport, which means there should at least be one step other than transport with substantial control.
89 citations
TL;DR: The effect of apoE on hepatic VLDL production is independent of the presence of the LDLr, and the composition of nascent V LDL was similar for both strains.
21 citations
TL;DR: The results show that APOE3Leiden does not prevent development of a fatty liver and does not normalize VLDL-TG secretion in mice with an apoE-deficient background, and it is concluded that apOE-mediated stimulation of V LDL secretion is isoform specific.
Abstract: Apolipoprotein E (apoE)-deficient mice develop hepatic steaatosis and show impaired very low density lipoprotein (VLDL)-triglyceride (TG) secretion. These effects are normalized on the introduction of the human APOE3 gene. To assess whether this apoE effect is isoform specific, we studied hepatic lipid metabolism in mice expressing either APOE3 or the mutant APOE3Leiden on apoe-/- or apoe+/- backgrounds. The transgenes were expressed mainly in periportal hepatocytes, as revealed by in situ hybridization. Mice expressing APOE3Leiden, on the apoe-/and apoe+/- backgrounds, had fatty livers, which were absent in APOE3/apoe-/- mice. APOE3Leiden/apoe-/mice showed a strongly reduced VLDL-TG secretion compared with APOE3/apoe-/- mice (48± 14 versus 82± 10 μmol/kg per hour, respectively). The presence of a single mouse apoe allele increased VLDL-TG secretion in APOE3Leiden/apoe +/- mice (121±43 μmol/kg per hour) compared with APOE3Leiden/apoe-/- mice. These results show that APOE3Leiden does not prevent development of a fatty liver and does not normalize VLDL-TG secretion in mice with an apoE-deficient background. The presence of a single mouse apoe allele is sufficient to normalize the APOE3Leiden-associated reduction of VLDL-TG secretion but does not prevent steatosis. We conclude that apoE-mediated stimulation of VLDL secretion is isoform specific. Chemicals/CAS: apolipoprotein E3 (Leidein); Apolipoprotein E3; Apolipoproteins B; Apolipoproteins E; Lipoproteins, VLDL; Protein Isoforms; RNA, Messenger; Triglycerides; very low density lipoprotein triglyceride
21 citations