Guanosine pentaphosphate

Guanosine pentaphosphate (also known as pppGpp) is a guanosine derivative that is involved in the stringent response, a regulatory response to amino acid starvation in bacteria. It is a nucleotide composed of guanosine and five phosphate groups.

Structure

Guanosine pentaphosphate is a guanosine triphosphate (GTP) derivative with two additional phosphate groups. The guanosine molecule is attached to a chain of five phosphate groups, hence the name "pentaphosphate". The structure of pppGpp is similar to that of other guanosine phosphates, with the addition of the two extra phosphate groups.

Function

Guanosine pentaphosphate plays a crucial role in the stringent response, a regulatory mechanism in bacteria that responds to amino acid starvation. When amino acids are scarce, the production of pppGpp increases. This molecule then binds to the RNA polymerase, inhibiting the transcription of rRNA and tRNA genes, which are involved in protein synthesis. This allows the bacteria to conserve resources until conditions improve.

In addition to its role in the stringent response, pppGpp also regulates other cellular processes. For example, it has been shown to inhibit the activity of GTPase enzymes, which are involved in signal transduction and protein synthesis.

Biosynthesis

The biosynthesis of guanosine pentaphosphate is catalyzed by the enzyme RelA. When amino acids are scarce, uncharged tRNA molecules accumulate in the cell. These uncharged tRNAs bind to the ribosome, triggering the activation of RelA. This enzyme then catalyzes the conversion of GTP to pppGpp.

Role in disease

Alterations in the levels of pppGpp have been associated with various diseases. For example, high levels of this molecule have been found in patients with tuberculosis, suggesting a role in the pathogenesis of this disease. Furthermore, some bacteria use the stringent response to survive in hostile environments, such as those encountered within the human body during infection.

See also

• Guanosine
• Stringent response
• RelA
• GTPase