Highlights Biotechnology and Human Health

1. Biotechnology plays an important role in human health today and that role will only increase in the future. In order to understand how biotechnology can play this role, it is important to understand some important physiological processes where problems arise.

2. Heart attacks have two common causes involving blockages - some caused by cholesterol-containing complexes and some caused by blood clots. We will consider blood clotting here.

3. Blood clotting is an essential process for organisms to survive. Without clotting, a single cut would kill an organism because it would cause it to lose all of its blood.

4. For blood clotting to be effective, it must be a) fast and b) efficient.

5. Blood clotting works because the blood carries the precursor proteins necessary for the clotting process in high abundance.

6. Blood clotting occurs because of the conversion of the inactive protein called fibrinogen to the active clot forming protein called fibrin. Fibrin is able to self-assemble itself into a 'web' of fibers so tight that it is impermeable to liquid. Hence, blood blood is stopped by the formation of the clot.

7. Activation of fibrinogen is catalyzed by the enzyme called thrombin. Thrombin exists normally in the blood as an inactive precursor called prothrombin. Two different "cascading" pathways resulting from cuts or injuries lead to conversion of the inactive prothrombin to the active thrombin.

8. Pathways of cascades, such as those that activate prothrombin to thrombin, work because they are very fast and increase the "signal" enormously. Activation of the first enzyme in the cascade leads to activation of dozens more, which lead to hundreds more at the next step, which lead to thousands more at the next stage.

9. Hemophilia arises from deficiency of enzymes in the cascade that activates prothrombin to thrombin. In theory, deficiency of any of the enzymes in the cascade can lead to an inability to form clots, but in reality, two proteins are most commonly missing in hemophilia.

10. A disease relating to the metabolism of porphyrin rings found in hemoglobin is called porphyria and has been speculated to be the source of legends of vampires and werewolves. You can read about it HERE (near the bottom of the page).

11. Production of recombinant versions of the missing proteins for hemophiliacs gives a simpler, safer, and less expensive source of these essential enzymes, eliminating the need to expose sufferers to blood-borne diseases.

12. Some compounds that reduce the ability of blood to clot are important. Heparin is a natural compound produced by the body that reduces blood clotting.

13. Cumarin (also called coumadin or warfarin) is referred to as a "blood thinner". It works by inhibitng action of Vitamin K. Vitamin K plays an important role in helping prothrombin to become activated. By inhibiting Vitamin K, cumarin reduces the ability of blood to clot. People who are given cumarin are those who are susceptible to excessive blood clotting. It is important to "balance" the proper amount of cumarin they take so as to prevent them from hemorrhaging. This latter phenomenon can lead to stroke and is the mechanism that Warfarin employs when it is used as a rat poison.

14. Aspirin acts also as a blood thinner, but by a different mechanism. Aspririn inhibits production of a class of compounds known as prostaglandins and these compounds help to make blood platelets "stickier." The stickiness of blood platelets is a factor in blood clotting. Inhibition of prostaglandin synthesis by aspirin is also why some people experience stomach problems. Prostaglandins are necessary for maintenance and growth of tissue lining the intestines.

15. Another anti-coagulant is hirudin. This compound is found in the saliva of leeches and they use it to keep blood from clotting while they are sucking blood from a victim.

16. Another factor related to reducing blood clotting is desmoteplase and is found in vampire bats. It is a version of t-PA and it acts to activate plasminogen to plasmin and thus help to disssolve clots that form when the bat bites a victim.

17. Removal of clots is also important in the body. Clots are dissolved by action of an enzyme called plasmin. Plasmin is found in abundance in the bloodstream in an inactive form called plasminogen. Conversion of plasminogen to plasmin is catalyzed by an enzyme called t-PA. t-PA was the first recombinant human protein approved for use by the FDA.

18. t-PA is used commonly to remove clots in the heart and is sometimes given to patients who have had a stroke. Administration of t-PA within a couple of hours of a stroke can lessen its severity.