LIPIDS II
Lipids I Lipid MiniTopics
Review
 Elmhurst College
Steroids Sphingolipids  Chemistry Department
Prostaglandins  Virtual ChemBook


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Prostaglandins

Introduction:

Prostaglandins were first discovered and isolated from human semen in the 1930s by Ulf von Euler of Sweden. Thinking they had come from the prostate gland, he named them prostaglandins. It has since been determined that they exist and are synthesized in virtually every cell of the body.

Prostaglandins, are like hormones in that they act as chemical messengers, but do not move to other sites, but work right within the cells where they are synthesized.

Prostaglandins are unsaturated carboxylic acids, consisting of of a 20 carbon skeleton that also contains a five member ring. They are biochemically synthesized from the fatty acid, arachidonic acid. See the graphic on the left.

The unique shape of the arachidonic acid caused by a series of cis double bonds helps to put it into position to make the five member ring. See the prostaglandin in the next panel.

Arachidonic Acid - Chime in new window

 

 Quiz: How many double bonds are in arachidonic acid?  




Prostaglandin Structure:

Prostaglandins are unsaturated carboxylic acids, consisting of of a 20 carbon skeleton that also contains a five member ring and are based upon the fatty acid, arachidonic acid. There are a variety of structures one, two, or three double bonds. On the five member ring there may also be double bonds, a ketone, or alcohol groups. A typical structure is on the left graphic.

Prostaglandin - Chime in new window

 

Quiz: In PGE2, list all of the functional groups.  
What is difference the C=C double bonds?  

Functions of Prostaglandins:

There are a variety of physiological effects including:

1. Activation of the inflammatory response, production of pain, and fever. When tissues are damaged, white blood cells flood to the site to try to minimize tissue destruction. Prostaglandins are produced as a result.

2. Blood clots form when a blood vessel is damaged. A type of prostaglandin called thromboxane stimulates constriction and clotting of platelets. Conversely, PGI2, is produced to have the opposite effect on the walls of blood vessels where clots should not be forming.

3. Certain prostaglandins are involved with the induction of labor and other reproductive processes. PGE2 causes uterine contractions and has been used to induce labor.

4. Prostaglandins are involved in several other organs such as the gastrointestinal tract (inhibit acid synthesis and increase secretion of protective mucus), increase blood flow in kidneys, and leukotriens promote constriction of bronchi associated with asthma.



Effects of Aspirin and other Pain Killers:

When you see that prostaglandins induce inflammation, pain, and fever, what comes to mind but aspirin. Aspirin blocks an enzyme called cyclooxygenase, COX-1 and COX-2, which is involved with the ring closure and addition of oxygen to arachidonic acid converting to prostaglandins. The acetyl group on aspirin is hydrolzed and then bonded to the alcohol group of serine as an ester. This has the effect of blocking the channel in the enzyme and arachidonic can not enter the active site of the enzyme.

By inhibiting or blocking this enzyme, the synthesis of prostaglandins is blocked, which in turn relives some of the effects of pain and fever.

Aspirin is also thought to inhibit the prostaglandin synthesis involved with unwanted blood clotting in coronary heart disease. At the same time an injury while taking aspirin may cause more extensive bleeding.

See the following chime tutorial for the detailed molecular basis for the inhibition of the COX enzyme by aspirin.

Chime Tutorial on action of COX enzyme with aspirin. Interactive Biochemistry was created by Edward K. O'Neil and Charles M. Grisham at the University of Virginia in Charlottesville,
Virginia.