title: Cellular responses to L-serine in Saccharomyces cerevisiae: roles of general amino acid control, compartmentalization, and aspartate synthesis.
abstract: In addition to its other roles, L-serine functions in one-carbon metabolism and is interconvertable with glycine via serine hydroxymethyltransferases. However, the transcriptional response by Saccharomyces cerevisiae to L-serine addition is markedly different from that to glycine, with L-serine acting as a nutrient source rather than one-carbon units. Following addition of excess L-serine, 743 genes showed significant expression changes. Induced functions included amino acid synthesis, some stress responses, and FeS metabolism, while ribosomal RNA processing, ribosome biogenesis and hexose transport were repressed. A co-regulated network of ten transcription factors could together control more than 90% of the induced and repressed genes forming a general response to changes induced by other amino acids or stresses and including the general amino acid control system usually activated in response to starvation for amino acids. A specific response to L-serine was induction of CHA1 encoding serine (threonine) dehydratase. L-serine addition resulted in a substantial transient increase in L-aspartate, which is, rather than L-glutamate, the major metabolite for short-term storage of ammonia derived from degradation of L-serine. L-aspartate synthesis was exclusively through mitochondrial metabolism of L-serine to pyruvate and ammonia, involving Cha1p, cytoplasmic pyruvate carboxylases Pyc1p and Pyc2p, and the cytoplasmic aspartate aminotransferase Aat2p.
authors.affiliation: Ramaciotti Center for Gene Function Analysis and School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Johnny C-Y
authors.initials: JC
authors.lastname: Lee
authors.forename: Abraham
authors.initials: A
authors.lastname: Tsoi
authors.forename: Geoffrey D
authors.initials: GD
authors.lastname: Kornfeld
authors.forename: Ian W
authors.initials: IW
authors.lastname: Dawes
mesh_terms: D001224:Aspartic Acid / Q000378:metabolism*; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects*; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000378:metabolism*; D012694:Serine / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D001224:Aspartic Acid; D012694:Serine
keywords: general amino acid control; l-aspartate accumulation; l-serine metabolism; stress responses; transcription