Cellular responses to L-serine in S accharomyces cerevisiae: roles of general amino acid control, compartmentalization, and aspartate synthesis

• Published in: FEMS yeast research 2013-11, Vol.13 (7), p.618-634
• Main Authors: Lee, Johnny C-Y, Tsoi, Abraham, Kornfeld, Geoffrey D, Dawes, Ian W
• Format: Article
• Language: English
• Subjects: Amino acids
• ISSN: 1567-1356; 1567-1364
• DOI: 10.1111/1567-1364.12063

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 S accharomyces 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 F e S 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 C ha1p, cytoplasmic pyruvate carboxylases P yc1p and P yc2p, and the cytoplasmic aspartate aminotransferase A at2p.