Galactose metabolism in yeast-structure and regulation of the leloir pathway enzymes and the genes encoding them.
The enzymes of the Leloir pathway catalyze the conversion of galactose to a more metabolically useful version, glucose-6-phosphate. This pathway is required as galactose itself cannot be used for glycolysis directly. In most organisms, including the yeast Saccharomyces cerevisiae, five enzymes are required to catalyze this conversion: a galactose mutarotase, a galactokinase, a galactose-1-phosphate uridyltransferase, a UDP-galactose-4-epimerase, and a phosphoglucomutase. In yeast, the genes encoding these enzymes are tightly controlled at the level of transcription and are only transcribed under specific sets of conditions. In the presence of glucose, the genes encoding the Leloir pathway enzymes (often called the GAL genes) are repressed through the action of a transcriptional repressor Mig1p. In the presence of galactose, but in the absence of glucose, the concerted actions of three other proteins Gal4p, Gal80p, and Gal3p, and two small molecules (galactose and ATP) enable the rapid and high-level activation of the GAL genes. The precise molecular mechanism of the GAL genetic switch is controversial. Recent work on solving the three-dimensional structures of the various GAL enzymes proteins and the GAL transcriptional switch proteins affords a unique opportunity to delve into the precise, and potentially unambiguous, molecular mechanism of a highly exploited transcriptional circuit. Understanding the details of the transcriptional and metabolic events that occur in this pathway can be used as a paradigm for understanding the integration of metabolism and transcriptional control more generally, and will assist our understanding of fundamental biochemical processes and how these might be exploited.
Sellick
Christopher A
CA
Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.
Campbell
Robert N
RN
Reece
Richard J
RJ
D005656:Fungal Proteins / Q000096:biosynthesis*; D005690:Galactose / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D015966:Gene Expression Regulation, Fungal / Q000502:physiology*; D004718:Saccharomycetales / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*
D005656:Fungal Proteins; D005690:Galactose