Lecture 5:  8-30-06

 

I. Amino Acids (continued)

 

Amino Acids with hydroxyl group: Refer previous lecture notes for structure:

1. Serine.

2. Threonine.

3. Phenylalanine.

4. Tyrosine.

 

IA. General Properties:

 

  1. Serine and Threonine have hydroxyl groups attached to the aliphatic side chains that impart hydrophilic character and make them more reactive than their structural relative’s alanine and valine, whereas

 

  1. Phenylalanine and Tyrosine are aromatic aminoacids have hydrophobic character.

 

3.     However, note that the hydroxyl group of the tyrosine is reactive when compared with the sidechains of other aliphatic amino acids.

 

4.     These OH- groups can be phosphorylated by reactions catalyzed by enzymes called kinases, which involves ATP molecules as a source of phosphate.

 

5.     The Phosphorylation of the hydroxyl group is necessary for a cascade of reactions called as signal transduction.

 

II. Why amino acids are so essential?

 

 

 

 

The following examples would explain how these aminoacids play an crucial role in cellular processes.

 

    1. Cancer is caused due to aberrations in the growth related genes.

 

    1. The aberration results in uncontrollable growth of cells.

 

    1. In normal cases such as in wound healing the cells stop growing when they contact adjacent cells. This phenomenon is called contact inhibition.

 

4.     In cancerous cells the ability to sense the own kind adjacent to it is lost resulting in cancerous growth.

 

  1. This is due to the mutations that occur in the DNA that carries all the information regarding the protein that is responsible for contact inhibition.

 

  1. These mutations can be caused by various factors. One such factor is viruses such as AIDS virus or Human Pappiloma Virus.

 

 

III. Initially Central Dogma was:

 

DNA    RNA    Protein

 

However, in viruses:

RNA    DNA

 

IIIA. How viruses cause cancer and how is serine and tyrosine involved in this?

 

1.   Viral genome is made of RNA.

 

2. The viruses that can make DNA from RNA are called reteroviruses using an enzyme called reverse transcriptase.

 

  1. These viruses carry a typical gene called oncogene that transforms the normal cells into cancerous cells by affecting the contact inhibition of cell growth.

 

  1. Normal cells grow as a monolayer whereas the cancerous cells grow haphazardly and form a lump.

 

  1. In addition the cancerous cells can become mobile in some cases called metastasis resulting in malignancy.

 

  1. All cells communicate with each other by means of many chemicals that are released in the medium that bind to the receptors (proteins that are present on cell membranes) of the other cells and elicit a response. Example: EGFR (Endodermal growth factor receptor), platelet receptor etc.

 

  1. These proteins have specific structure and shape.

 

  1. The cells synthesize growth factors that tell other cells near it to grow by binding to these EGFR, which then signal pathways downstream.

 

  1. The binding of growth factor causes conformational changes in the EGFR, which triggers its kinase activity.

 

  1. Kinases are enzymes that phosphorylate some functional groups of amino acids.

 

Protein-OH + ATP    Protein-OPO3H2 +ADP

 

 

 


 


11.  The functional groups that typically get phosphorylated are the hydroxyl groups of serine, threonine, phenylalanine and tyrosine.

 

12.  The phosphorylation reaction triggers a cascade of reactions involving many proteins that induces cells division.

 

  1. The activation involves conformational changes of the proteins.

 

  1. In the case of cancer, the normal gene involved is mutated in the EGFR cascade and thus is constantly activated to induce cell growth and division.

 

  1. This results in cell growth even in the absence of endodermal growth factor (EGF).

 

IIIB. Which amino acid is mutated in the kinase that causes uncontrollable growth of cells?

In most cases it is the Serine that is mutated into tyrosine.

 

 

IV. Swapping of parts of chromosomes can cause serious abnormalities due to overproduction of protein kinases:

 

 

 


 

 

 

 

IVA. Where is phenylalanine involved?