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

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.