Guanosine pentaphosphate

(p)ppGpp, guanosine pentaphosphate or teraphosphate is an alarmone which is involved in the stringent response in bacteria, causing the inhibition of RNA synthesis when there is a shortage of amino acids present. This causes translation to decrease and the amino acids present are therefore conserved. (p)ppGpp is an effector molecule which is produced as a result of amino acid starvation within a bacterial cell.

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(p)ppGpp is created via pppGppp synthase, also known as "Rel A", and is converted from pppGpp to ppGpp via pppGpp phosphohydrolase. Rel A is associated with about every one in two hundred ribosomes and it becomes activated when an uncharged Transfer RNA (tRNA) molecule enters the A site of the ribosome, due to the shortage of amino acid required by the tRNA. If a mutant bacterium is relA^- it is said to be relaxed and no regulation of RNA production due to amino acid absence is seen.

Targets of (p)ppGpp include rRNA operons, of which there are 7, all of which have 2 promoters. when (p)ppGpp associates with the promoter it stops the RNA polymerase enzyme from being able to bind and initiate transcription. It is thought that (p)ppGpp may affect the stability of the open complex of the RNA polymerase and DNA or it may affect promoter clearance. Its presence also leads to an increase in pausing during elongation and it competes with nucleoside triphosphate substrates.

When the amino acid balance in the cell is restored, (p)ppGpp is hydrolysed by SpoT.