Regulation of phosphoglycerate dehydrogenase levels and effect on serine synthesis in Escherichia coli K-12.
The level of phosphoglycerate dehydrogenase, the first enzyme in the biosynthetic pathway to serine and glycine, has been studied in Escherichia coli grown under different conditions. The enzyme level was not reduced by growth in a medium which contained the end products of the pathway, nor was it elevated when the growth rates was limited by the supply of serine. Elevation of phosphoglycerate dehydrogenase did not occur when charging of tRNA ser was inhibited by serine hydroxamate. However, phosphoglycerate dehydrogenase levels were subject to regulation. Elevated levels of enzyme activity were observed in merodiploids containing multiple copies of the serA gene, and lowered enzyme levels were found in cells grown on carbon sources other than glucose or when certain amino acids were present in the growth medium. The combined effect of these nutritional changes (carbon source and amino acids) reduced the level of phosphoglycerate dehydrogenase to 10 to 12% of that found in wild-type cells and to about 5% of the level in the merodiploids. By using antibody prepared against purified phosphoglycerate dehydrogenase we established that the decrease in enzyme activity reflected decreased amounts of enzyme protein. Constant intracellular concentrations of 3-phosphoglycerate and serine were found in cells with marked differences in phosphoglycerate dehydrogenase activity, indicating that end product inhibition of phosphoglycerate dehydrogenase activity, rather than the amount of the biosynthetic enzymes, is the major factor in regulating the intracellular concentration of serine.
D000596:Amino Acids / Q000494:pharmacology; D002237:Carbohydrate Dehydrogenases / Q000378:metabolism*; D004926:Escherichia coli / Q000201:enzymology* / Q000235:genetics; D005796:Genes; D005988:Glyceric Acids / Q000378:metabolism; D005998:Glycine / Q000378:metabolism; D007700:Kinetics; D007773:Lactates / Q000494:pharmacology; D050543:Phosphoglycerate Dehydrogenase; D012694:Serine / Q000096:biosynthesis*
D000596:Amino Acids; D005988:Glyceric Acids; D007773:Lactates; D012694:Serine; D002237:Carbohydrate Dehydrogenases; D050543:Phosphoglycerate Dehydrogenase; D005998:Glycine