13 - Intro to Lipid Protein Phosphorylation Flashcards
Where is phosphorus found in biological systems?
In biological systems phosphorus is found as a free phosphate ion in solution and is called inorganic phosphate
What form are phosphates most commonly found in?
However, phosphates are most commonly found in the form of adenosine phosphates (AMP, ADP, and ATP) and can be released by hydrolysis
o E.g., ATP to ADP, and ADP to AMP
What do phosphoanhydride bonds contain?
Phosphoanhydride bonds in ADP and ATP contain high amounts of energy which give them their vital role in all living organisms
In regards to phosphate, what is a pivotal strategy in the regulation of cellular processes?
The addition and removal of phosphate from proteins in all cells in a pivotal strategy in the regulation of cellular processes
Why is reversible phosphorylation important?
Reversible phosphorylation of proteins is an important regulatory mechanism that occurs in both prokaryotic and eukaryotic organisms
o Approximately 10% of the proteins in the cell cytosol are phosphorylated
Phosphorylation and dephosphorylation reactions
The reaction involved ATP as the phosphoryl donor in the phosphorylation reaction and hydrolysis of the phosphoryl group in the dephosphorylation reaction
o Phosphorylation: E + ATP -> E-P + ADP (E is enzyme)
o Dephosphorylation: E-P + H2O -> E + Pi
o NET: ATP + H2O -> ADP + Pi
Hydrolysis of ATP energy
- The net result of these reactions can be viewed as the hydrolysis of ATP, which has a deltaG of -12kCal/mol under cellular conditions and is therefore, energetically favourable
Where does protein phosphorylation usually occur?
Protein phosphorylation usually occurs on serine, threonine, and tyrosine residues in eukaryotic proteins
o In addition, phosphorylation occurs on the basic amino acid residues histidine, arginine or lysine in prokaryotic proteins
How does a hydrophobic portion of a protein become polar and hydrophobic?
The addition of a phosphate (PO4) molecule to an R group of an amino acid residue can turn a hydrophobic portion of a protein into a polar and extremely hydrophilic portion of a molecule
- This can introduce and conformational change in the structure of the protein
o This is important because the change can lead to triggering on enzyme activity so it is able to do its catalytic job
What do phosphorylated amino acids do?
Phosphorylated amino acids can also serve as docking sites for module signal transduction proteins (SH2, SH3, and PTB domains)
o These proteins dock with the phosphorylated amino acids which build complexes of multi protein which sere for signal transduction
How can a protein be phosphorylated?
If we have a protein with an amino acid side chain it can be phosphorylated removing a hydrogen, and leading to the covalent addition of phosphate which is negatively charged
o The X is an oxygen, nitrogen, or sulphate residue on an amino acid side chain in a protein
o To make the phosphorylation more readily, to make it more eas to take place, we can couple the hydrolysis of ATP,
Kinases catalyses the hydrolysis, helping the transfer of phosphate onto the target protein
o We have to then switch off the signal once its generated, this involves phosphatases which takes water and allows the hydrolysis of the phosphate which moves the protein into its original state
o This is a molecular switch
What do the amino acids serine, threonine, and tyrosine have?
these amino acids have a hydroxyl group which the kinases can act upon, allowing the addition of a phosphate group
Enzymes that act on amino acids and phosphor-amino acids
o Serine/threonine kinase can act upon the serine and threonine
o Serine/threonine phosphatase acts upon the phophoserine and phosphothreonine removing the phosphate and returning it to its resting state
o Tyrosine kinase acts upon tyrosine, and tyrosine phosphotyrosine acts on phosphotyrosine
o The tyrosine kinase and serine/threonine kinase recognises the amino acids surrounding these specific amino acids, almost acting like a postcode for the enzyme
What kind of change does protein phosphorylation cause?
Protein phosphorylation can cause conformational change, for example activation or inactivation of an enzyme
- it can lead to complex formation (serving as docking sites)
- it can trigger the ubiquitin-proteasome pathway leading to degradation, and in terms of regulation, there is a class of proteins called 14-3-3 proteins which recognise phosphoserine and threonine residues, and these proteins then dock and interact with them which inactivates the proteins (sequestration)
