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Index >> Metabolic Regulation >> Catabolite Repression

Catabolite Repression

Catabolite Repression - When E.Coli is grown in a medium containing two carbon compounds such as glucose and lactose, growth is characterized by two exponential phases separated by a distinct lag phase (diauxic growth). In this case, glucose is first utilized and, during the second growth period lactose is utilized.

The enzymes necessary for metabolising lactose, such as β-galactosidase etc., are not synthesized until the glucose concentration in the medium is reduced although the inducer (lactose) is present.

Thus, the induction of β-glactosidase is prevented by the presence of glucose in the growth medium. This kind of control mechanism by glucose was called as glucose effect. It is now known that all rapidly metabolizable energy sources repress the formation of the enzymes necessary for the utilization of carbon sources that are slowly utilized and this phenomenon is now also known as catabolite repression

The mechanism by which catabolite repression functions is now fairly well understood. It is believed that the extent of catabolite repression depends upon the concentration of c.AMP (3'-5 cyclic adenosine monophosphate) inside the cells. An allosteric pro­tein called the catabolite activator protein (CAP), a dimer molecule of 44,000 daltons molecular weight is responsible for the regulation of enzymes under this type of control.

Cyclic AMP which is synthesized from ATP is the effector. When cells are grown on rapidly metabolizable carbon substrates such as glucose, the intracellular concentration of c-AMP is low and ,vice versa. The high concentration of glucose prevents the functioning of adenly cyclase, the enzyme involved in the conversion of AMP to c-AMP. Binding of c-AMP to CAP causes it to undergo a transition which allows it to bind to the DNA in the promotor region and thereby permits transcription. Thus both CAP protein and a high concentration of c­AMP are essential to allow the synthesis of enzymes that are subject to catabolite repression.

cAMP does not directly promote m-RNA synthesis but controls by binding to the CAP and by doing so, increases the rate of transcription of the adjacent operons. CAP therefore, is a positive control element for all glucose sensitive operons. The binding of neither CAP nor a specific repressor has any influence on the rate of m-RNA chain growth.

Instead, the CAP acts positively and the repressor, negatively by controlling the rate at which RNA polymerase molecules attach to promotors (Regions of DNA involved in the initiation of transcription).

Binding of the repressor to the operator prevents the RNA polymerase from binding to the promotor region. The lactose operon is a good example of a regulatory system that is both under positive and negative control, The positive control is exerted through the CAP protein while the negative control is functional through the repressor protein.

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