Linked Life Data

20964315

Source:http://linkedlifedata.com/resource/pubmed/id/20964315

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2010-12-3
pubmed:abstractText
Metabolomics is a powerful method of examining the intricate connections between mutations, metabolism, and disease. Metabolic footprinting examines the extracellular metabolome or exometabolome. We employed NMR-based metabolic footprinting and multivariate statistical analysis to examine a yeast model of mitochondrial dysfunction. Succinate dehydrogenase (SDH) is a component of both the tricarboxylic acid cycle and the mitochondrial respiratory chain. Mutations in the human SDH are linked to a variety of cancers or neurodegenerative disorders, highlighting the genotype/phenotype complexity associated with SDH dysfunction. To gain insight into the underlying global metabolic consequences of SDH dysfunction, we examined the metabolic footprints of SDH3 and SDH4 mutants. We identified and quantified 36 metabolites in the exometabolome. Our results indicate that SDH mutations cause significant alterations to several areas of yeast metabolism. Multivariate statistical analysis allowed us to discriminate between the different metabotypes of individual mutants, including mutants that were phenotypically indistinguishable. Metabotypes were highly correlated to mutant growth yields, suggesting that the characterization of metabotypes offers a rapid means of investigating the phenotype of a new mutation. Our study provides novel insight into the metabolic effects of SDH dysfunction and highlights the effectiveness of metabolic footprinting for examining complex disorders, such as mitochondrial diseases.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1535-3907
pubmed:author
pubmed:issnType
Electronic
pubmed:day
3
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6729-39
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Mutations in the Saccharomyces cerevisiae succinate dehydrogenase result in distinct metabolic phenotypes revealed through (1)H NMR-based metabolic footprinting.
pubmed:affiliation
Department of Biochemistry, School of Molecular & Systems Medicine, University of Alberta, Edmonton, Alberta, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't