title: Volatile anesthetics affect nutrient availability in yeast.
abstract: Volatile anesthetics affect all cells and tissues tested, but their mechanisms and sites of action remain unknown. To gain insight into the cellular activities of anesthetics, we have isolated genes that, when overexpressed, render Saccharomyces cerevisiae resistant to the volatile anesthetic isoflurane. One of these genes, WAK3/TAT1, encodes a permease that transports amino acids including leucine and tryptophan, for which our wild-type strain is auxotrophic. This suggests that availability of amino acids may play a key role in anesthetic response. Multiple lines of evidence support this proposal: (i) Deletion or overexpression of permeases that transport leucine and/or tryptophan alters anesthetic response; (ii) prototrophic strains are anesthetic resistant; (iii) altered concentrations of leucine and tryptophan in the medium affect anesthetic response; and (iv) uptake of leucine and tryptophan is inhibited during anesthetic exposure. Not all amino acids are critical for this response since we find that overexpression of the lysine permease does not affect anesthetic sensitivity. These findings are consistent with models in which anesthetics have a physiologically important effect on availability of specific amino acids by altering function of their permeases. In addition, we show that there is a relationship between nutrient availability and ubiquitin metabolism in this response.
authors.affiliation: Department of Biochemistry and Molecular Biology, The Milton S. Hershey Medical Center, The Pennsylvania State University, Hershey, Pennsylvania 17033, USA.
authors.forename: Laura K
authors.initials: LK
authors.lastname: Palmer
authors.forename: Darren
authors.initials: D
authors.lastname: Wolfe
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Keeley
authors.forename: Ralph L
authors.initials: RL
authors.lastname: Keil
mesh_terms: D026905:Amino Acid Transport Systems / Q000235:genetics / Q000502:physiology*; D026923:Amino Acid Transport Systems, Basic / Q000235:genetics / Q000378:metabolism; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D025141:Drug Resistance, Fungal / Q000235:genetics; D007530:Isoflurane / Q000494:pharmacology*; D007930:Leucine / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017422:Sequence Analysis, DNA; D014364:Tryptophan / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D026905:Amino Acid Transport Systems; D026923:Amino Acid Transport Systems, Basic; D018685:Anesthetics, Inhalation; C430023:LYP1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C470089:TAT1 protein, S cerevisiae; D025801:Ubiquitin; D014364:Tryptophan; D007530:Isoflurane; D007930:Leucine