Stringent response

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The stringent response (German sometimes also "stringent answer" or "stringent control") is an adaptation of the metabolism of prokaryotes to an undersupply of nutrients such as carbon or amino acids . It manifests itself through an increased stress resistance of the cell, a strongly slowed growth and a clearly reduced metabolism; the cell goes into a kind of hibernation, so to speak.

Signal path

If there is a lack of nutrients, guanosine triphosphate (GTP) and adenosine triphosphate (ATP) form the signaling molecules guanosine tetraphosphate (ppGpp) and guanosine pentaphosphate (pppGpp). These molecules act as "alarmones" and influence up to a third of all genes in the cell via a global regulatory network.

In Escherichia coli , this reaction is catalyzed by the two enzymes RelA / L11A (ppGpp synthase I) and SpoT (ppGpp synthase II). There are at least two ways to trigger the stringent response:

  • If there is a lack of amino acids, tRNAs remain unloaded in the affected cell . In addition to terminating translation, these lead to an activation of RelA on the ribosome , which leads to the formation of ppGpp and pppGpp.
  • The formation of pppGpp can also be triggered by SpoT due to carbon deficiency , although the exact mechanism is still unknown.

Effects

In stringent response, ppGpp and pppGpp directly inhibit a number of metabolic processes, including the synthesis of RNAs and protein biosynthesis via the inhibition of RNA polymerases . In addition, a number of biosynthetic and catabolic operons are activated in order to be able to use other nutrient sources.

Furthermore, the synthesis of phospholipids and nucleotides as well as cell division are inhibited via various signal transduction pathways . On the other hand, the transcription accuracy is increased, the synthesis of proteins to combat stress, including chaperones, is increased and protein breakdown is promoted.

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