Stringent response
Encyclopedia
The stringent response is a stress response that occurs in bacteria and plant chloroplasts in reaction to amino-acid starvation , fatty acid limitation , iron limitation , heat shock and other stress conditions. The stringent response is signaled by the alarmone
Alarmone
Alarmone is an intracellular signal molecule that is produced due to harsh environmental factors. They regulate the gene expression at transcription level. Alarmones are produced in high concentrations when harsh environmental factors occur in bacteria and plants, such as lack of amino acids to...

 (p)ppGpp, and modulating transcription of up to 1/3 of all genes in the cell. This in turn causes the cell to divert resources away from growth and division and toward amino acid synthesis in order to promote survival until nutrient conditions improve.

In Escherichia coli (p)ppGpp production is mediated by the ribosomal protein L11 and the ribosome-associated protein RelA with the A-site bound deacylated tRNA being the ultimate inducer . RelA converts GTP
Guanosine triphosphate
Guanosine-5'-triphosphate is a purine nucleoside triphosphate. It can act as a substrate for the synthesis of RNA during the transcription process...

 and ATP
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...

 into pppGpp by adding the pyrophosphate from ATP onto the 3' carbon of the ribose in GTP releasing AMP
Adenosine monophosphate
Adenosine monophosphate , also known as 5'-adenylic acid, is a nucleotide that is used as a monomer in RNA. It is an ester of phosphoric acid and the nucleoside adenosine. AMP consists of a phosphate group, the sugar ribose, and the nucleobase adenine...

. pppGpp is converted to ppGpp by the gpp gene product, releasing Pi
Phosphate
A phosphate, an inorganic chemical, is a salt of phosphoric acid. In organic chemistry, a phosphate, or organophosphate, is an ester of phosphoric acid. Organic phosphates are important in biochemistry and biogeochemistry or ecology. Inorganic phosphates are mined to obtain phosphorus for use in...

. ppGpp is converted to GDP
Guanosine diphosphate
Guanosine diphosphate, abbreviated GDP, is a nucleoside diphosphate. It is an ester of pyrophosphoric acid with the nucleoside guanosine. GDP consists of the pyrophosphate group, the pentose sugar ribose, and the nucleobase guanine....

 by the spoT
SpoT
SpoT is a bacterial protein that hydrolizes alarmones, ppGpp, in the bacterial stringent response. Its hydrolase activity is Mn2+-dependent with a conserved His-Asp motif. In E coli, SpoT protein consistent of 693 amino acids. SpoT is belongs to the RSH protein family.It is bifunctional, has both...

gene product, releasing pyrophosphate (PPi
Pyrophosphate
In chemistry, the anion, the salts, and the esters of pyrophosphoric acid are called pyrophosphates. Any salt or ester containing two phosphate groups is called a diphosphate. As a food additive, diphosphates are known as E450.- Chemistry :...

).
GDP is converted to GTP by the ndk gene product. Nucleoside triphosphate (NTP) provides the Pi, and is converted to Nucleoside diphosphate (NDP).

In other bacteria stringent response is mediated by a variety of RelA/SpoT Homologue (RSH) proteins , with some having only synthetic, or hydrolytic or both (Rel) activities.

During the stringent response, (p)ppGpp accumulation affects the resource-consuming cell process replication
DNA replication
DNA replication is a biological process that occurs in all living organisms and copies their DNA; it is the basis for biological inheritance. The process starts with one double-stranded DNA molecule and produces two identical copies of the molecule...

 and transcription
Transcription (genetics)
Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...

. (p)ppGpp is thought to bind RNA polymerase
RNA polymerase
RNA polymerase is an enzyme that produces RNA. In cells, RNAP is needed for constructing RNA chains from DNA genes as templates, a process called transcription. RNA polymerase enzymes are essential to life and are found in all organisms and many viruses...

 and alter the transcriptional profile, decreasing the synthesis of translational machinery (such as rRNA and tRNA), and increasing the transcription of biosynthetic genes. Additionally, the initiation of new rounds of replication is inhibited and the cell cycle arrests until nutrient conditions improve. Translational GTPases involved in protein biosynthesis are also affected by ppGpp, with Initiation Factor 2 (IF2) being the main target .

Chemical reaction catalyzed by RelA:

ATP + GTP ---> AMP
Adenosine monophosphate
Adenosine monophosphate , also known as 5'-adenylic acid, is a nucleotide that is used as a monomer in RNA. It is an ester of phosphoric acid and the nucleoside adenosine. AMP consists of a phosphate group, the sugar ribose, and the nucleobase adenine...

+ pppGpp

Chemical reaction catalyzed by SpoT:

ppGpp ---> GDP + PPi

Extensive Mendeley collection of scientific papers covering stringent response is available here.
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