title: Cellular stress created by intermediary metabolite imbalances.
abstract: Small molecules generally activate or inhibit gene transcription as externally added substrates or as internally accumulated end-products, respectively. Rarely has a connection been made that links an intracellular intermediary metabolite as a signal of gene expression. We report that a perturbation in the critical step of a metabolic pathway--the D-galactose amphibolic pathway--changes the dynamics of the pathways leading to accumulation of the intermediary metabolite UDP-galactose. This accumulation causes cell stress and transduces signals that alter gene expression so as to cope with the stress by restoring balance in the metabolite pool. This underscores the importance of studying the global effects of alterations in the level of intermediary metabolites in causing stress and coping with it by transducing signals to genes to reach a stable state of equilibrium (homeostasis). Such studies are an essential component in the integration of metabolomics, proteomics, and transcriptomics.
authors.affiliation: Laboratory of Molecular Biology, National Cancer Institute, Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, and Genome Analysis Unit, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Sang Jun
authors.initials: SJ
authors.lastname: Lee
authors.forename: Andrei
authors.initials: A
authors.lastname: Trostel
authors.forename: Phuoc
authors.initials: P
authors.lastname: Le
authors.forename: Rajendran
authors.initials: R
authors.lastname: Harinarayanan
authors.forename: Peter C
authors.initials: PC
authors.lastname: Fitzgerald
authors.forename: Sankar
authors.initials: S
authors.lastname: Adhya
mesh_terms: D001483:Base Sequence; D004926:Escherichia coli / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism*; D005690:Galactose / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D009154:Mutation; D009711:Nucleotides / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011743:Pyrimidines / Q000378:metabolism / Q000494:pharmacology; D013312:Stress, Physiological / Q000235:genetics*; D014534:UDPglucose 4-Epimerase / Q000235:genetics
chemical_list: D009711:Nucleotides; D011743:Pyrimidines; D014534:UDPglucose 4-Epimerase; C020551:galactose epimerase; C030986:pyrimidine; D005690:Galactose