Catabolite repression

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The catabolite is a mechanism for gene regulation . It is used to inhibit the production of certain catabolic enzymes in a cell, as long as a generally energetically more favorable substrate - typically a different carbon source - of an alternative catabolic metabolic pathway is available in significant quantities.

principle

In the case of catabolite repression, according to the original assumption, a catabolite of the glucose metabolism causes an inhibition of the gene expression of certain genes relevant for the processing of other carbon compounds, e.g. B. in the Lac operon . However, after naming the observed effect, it was discovered that it is not a glucose catabolite that inhibits gene expression, but rather the second messenger cAMP , which is formed when there is a glucose deficiency and which binds to the catabolite activator protein (CAP, also cAMP response protein , CRP). After cAMP binding, the dimeric CAP protein acts as an activator of gene expression. Glucose leads to a reduced cAMP concentration. Catabolite repression is thus an activation of gene expression in the absence of the substrate. In addition, the lac operon also has the lac repressor , which releases the promoter when allolactose (a metabolite of lactose ) binds .

This mechanism using the example that was shown for the first time glucose , which is why he used to be glucose effect was called. But other carbon sources can also be responsible for catabolite repression.

Lactose operon: cAMP as a hunger signal in bacteria. In order to survive in glucose (Glc) deficiency situations, the bacterium Escherichia coli has a controllable gene unit that enables the uptake and utilization of lactose (Lac) if necessary. This process requires two signals:
1. In the case of Glc deficiency, cAMP activates the CAP protein, which binds directly to the promoter (p) and supports its activation;
2. Allolactose binds to a repressor protein (REP); this then separates from the operator sequence (o) and releases the transcription of the lacZYA gene unit.
When Glc is available, the cAMP level falls through inhibition of adenylyl cyclase (AC).

It was noticed that certain metabolic pathways of a bacterium were inhibited (i.e. the synthesis of certain enzymes failed to occur) when glucose was present in the medium. In the absence or after consumption of the glucose, the previously repressed enzymes were expressed . This becomes particularly clear when Escherichia coli grows in a medium which contains lactose and glucose. At first, the culture grows relatively quickly and consumes the glucose, followed by a short phase without growth (lag phase or latency phase), and then growth continues with consumption of lactose, but more slowly. When E. coli grows on lactose, the lactose operon is induced. Initially, however, this induction was not carried out in favor of utilizing the glucose present in the medium. The short lag phase between complete utilization of glucose and the start of lactose utilization thus describes the period in which the lactose operon was induced and the lactose-utilizing enzymes were formed. Such a growth behavior with two separate exponential phases is also called diauxic growth or diauxia for short .

The mechanism underlying this phenomenon is catabolite repression. Glucose inhibits adenylate cyclase , an enzyme that synthesizes cyclic adenosine monophosphate (cAMP) from ATP . cAMP is a universal intracellular messenger substance or signal molecule (second messenger) and regulates many cellular processes. An important function of cAMP in the context described here is the binding to CAP (catabolite activator protein). In the case of catabolite-repressed genes, the RNA polymerase can only bind to the DNA and initiate transcription if CAP has previously been bound to the DNA. This addition can only take place with prior binding to cAMP. If the intracellular cAMP concentration drops, CAP-dependent genes cannot be transcribed and their products cannot be formed. The lactose operon is subject to this control mechanism, but it is not the only one. Since, on the one hand, many operons are controlled by means of the cAMP level and, on the other hand, operons usually have their own regulators (in the case of the lac operon: allolactose and the lac repressor), this simple regulation system enables cell metabolism to be modulated.

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Individual evidence

  1. ↑ a b c d e Jeremy M. Berg, John L. Tymoczko, Lubert Stryer : Biochemistry. 5th edition. Freeman, New York 2002, ISBN 0-7167-4684-0 , chapter 31.1.6. Available online at the NCBI Bookshelf.