Paigen, Kenneth (Roswell Park Memorial Institute, Buffalo, N.Y.). Role of the galactose pathway in the regulation of β-galactosidase. J. Bacteriol. 92:1394–1403. 1966.—Galactose and its metabolites, galactose-1-phosphate, uridine diphosphogalactose, and uridine diphosphoglucose, as well as metabolites derived from uridine diphosphoglucose, were tested for their role in the regulation of β-galactosidase. In cultures of wild-type Escherichia coli strains K-12 and B, exogenous galactose was no more effective as a repressor than were other carbon sources. Exogenous galactose also did not repress β-galactosidase when added to mutants which can accumulate intracellular galactose or galactose-1-phosphate, indicating that these compounds do not repress. In such strains, repression of β-galactosidase formation did occur if galactose was added in the presence of another metabolizable carbon source. This repression is presumably a consequence of the growth inhibition which follows the accumulation of these compounds, and the general catabolite repression which develops during growth inhibition. Exogenous galactose did repress β-galactosidase in a mutant which accumulates uridine diphosphogalactose. This appears to result from a combination of several factors. These include a general inhibition of protein synthesis through depletion of the uridine triphosphate pool, catabolite inhibition as a consequence of growth inhibition, as well as a specific inhibition of β-galactosidase formation. Glucose repression of β-galactosidase was normal in a mutant strain blocked in the formation of uridine diphosphoglucose from uridine triphosphate and glucose-1-phosphate, indicating that neither uridine diphosphoglucose nor any compound uniquely derived from it functions as the hypothetical catabolite repressor. It is concluded that at least two separate mechanisms exist for the endogenous repression of β-galactosidase in E. coli. One is exerted by uridine diphosphogalactose or its metabolic product; the other, by the generalized catabolite repressor which is still formed in strains unable to make uridine diphosphogalactose or uridine diphosphoglucose.