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The observation has been made repeatedly that the induced synthesis of many different enzymes can be inhibited by a wide variety of carbo

In previous papers a model (Cohn, 1956, 1958; Cohn and Horibata, 1959a, b) was described which completely rationalized the kinetics of the induction by galactosides and the inhibition by glucose in terms of the properties of the galactoside-permease. However, little information was provided on the mechanism by which glucose acts as an inhibitor of induction. It is known (Cohn and Horibata, 1959a, b; Herzenberg, 1958) that glucose inhibits induced f-galactosidase synthesis in mutants which lack permease, and, conversely, induced permease synthesis is inhibited in mutants which lack f3-galactosidase. Therefore, it is clear that the inhibiting action of glucose is not at the level of the activity of either permease or galactosidase but at some other point in the series of reactions leading to the synthesis of either component. The experiments described here are best understood in terms of the hypothesis that induced enzymes are those whose synthesis can be repressed (Neidhardt and Magasanik, 1956a, b; 1957; Vogel, 1957) by some derivative of the carbon source. The inducer relieves the repression. Certain very inhibitory carbohydrates, such as glucose or mannitol, are metabolized to yield high internal levels of repressor, whereas less inhibitory substances such as succinate and lactate give lower levels of repressor. The repressor-hypothesis with some qualifications will be used as the basis for the description of the data.

The kinetics of induction of the galactozymase of certain yeasts (Spiegelman, 1951) and the permease-3-galactosidase system of Escherichia coli (Monod, 1956) can, under certain conditions, be described as autocatalytic. Essentially two hypotheses have been proposed to account for such findings: (a) that the enzyme-forming system itself is autocatalytically activated (Campbell and Spiegelman, 1956) or self-reproducing (Spiegelman, 1946), or (b) that in some way the enzyme being induced intervenes in its own induction (Monod and Cohn, 1952). To evaluate these hypotheses, it should be recalled that the kinetics of formation of an enzyme by a population of cells describes events at the cellular level only if the response of each individual cell is simultaneous and equal (Benzer, 1953; Monod and Cohn, 1952). Such a response we term homogeneity. The first experimental analysis of this problem we owe to Benzer (1953) who defined the experimental conditions under which the induction of f-galactosidase would proceed in a homogeneous fashion in an E. coli (lac+) population. These were (a) conditions of gratuity, i. e., neither the presence of the enzyme itself nor its inducer influences general cellular metabolism, and (b) a saturating concentration of inducer. Benzer (1953) also showed that heterogeneity is generated under conditions of nongratuity. The question remained however as to what the response would be at nonsaturating concentrations of inducer.

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