Research Article 14: Cyclic Adenosine Monophosphate Diesterase Activity and Catabolite Repression in E. coli

Abstract

Exogenous 3′,5′ cyclic adenosine monophosphate (cyclic AMP) overcomes the inhibition of the synthesis of β-galactosidase and of other enzymes subject to regulation by catabolite repression (Perlman and Pastan, 1968a,b; Ullmann and Monod, 1968). There is evidence that both catabolite repression and its reversal by cyclic AMP affect transcription (Perlman and Pastan, 1968b; Pastan and Periman, 1968; Silverstone, Magasanik, Reznikoff, Miller, and Beckwith, 1969; Contesse, Crépin, and Gros, this volume). Little is known, however, about the mechanism by which an excess of catabolic over biosynthetic reactions leads to the inhibition of the transcription of genes that code for certain catabolic enzymes. Evidently an understanding of the mode of action of cyclic AMP will clarify the phenomenon of catabolite repression.

At least two mechanisms by which cyclic AMP overcomes catabolite repression may be envisaged. It may affect the interaction between RNA polymerase and the promoter (or an as yet unidentified regulatory gene adjacent to the promoter). Alternatively cyclic AMP may act as a "derepressor" by inactivating a hypothetical apo-repressor specific for catabolite repression. A third possibility that cyclic AMP in some manner lowers the rate of energy production and thus affects catabolite repression only indirectly is rendered unlikely by the recent finding (Chambers and Zubay, 1969) that cyclic AMP enhances the synthesis of β-galactosidase in a cell-free system where presumably little energy metabolism occurs. We found that cyclic AMP at a concentration of 5 × 10⁻³M slowed the rate of growth of strains AB 257 and K 12-3000 by 20 to 30 percent...