Enzymes in Medicine

Enzymes in Medicine are produced by living cells; they are the substances that act as a catalyst in the living organisms, increasing the rate at which reactions take place by lowering the activation energy, without affecting itself in the process. Therefore, they are also called as biological catalysts.

Without them, the reactions in the cells would proceed at a too slower rate to sustain life. They are able to speed up the rate of chemical reactions. All enzymes are proteins in nature and they have therefore a tertiary structure. Each enzyme has a specific shape with an active site, specific to one substrate molecule. When the substrate combines with the active site an enzyme-substrate complex is formed (Figure 1).
Enzyme           +          Substrate         =          Enzyme-Substrate Complex.

Figure 1 Enzyme-Substrate complex.

History

1830

In 1830 Dubrunfaut prepared an extract from malt, which converted starch into sugar.

1833

In 1833, Payen and Persoz precipitated a substance, by alcohol, from such extracts which could be dried and preserved. These had very powerful action on starch and they called them “diastase”.

1860’s

As more bodies of similar properties became known, the diastases were called “ferments” as they resemble the alcoholic fermentation in their activities. When Louise Pasteur showed that the fermentation was due to the presence of a living organism while diastase and “bodies like it” were distinguish as “soluble or unorganized ferments”, in contradiction to living organisms, like yeast, which went by the name “organized ferments”.

1874

In 1874, a Danish chemist Christian Hansen produced the first specimen of rennet by extracting dried calves’ stomachs with saline solution. Apparently this was the first enzyme preparation of relatively high purity used for industrial purposes.

1876

In 1876, William Kuhne proposed the name “enzyme” for the previously known “unorganized ferments”. The word “enzyme” itself means “in yeast” and is derived from the Greek;

en” meaning “in”,

and “zyme” meaning “yeast” or “leave”.

1897

In 1897, it was shown by German a chemist Edward Büchner that cell-free extracts of yeast could ferment sugars to alcohol and carbon dioxide; Büchner denoted his preparation “zymase”. This important achievement was the first indication that enzymes could function independently of the cell.

1902

In 1902, Scottish embryologist John Beard started treating cancer patients with living enzymes extracted from the pancreas.  His book “The Enzyme Treatment of Cancer” was published in 1911.

1932

Ernst Freund, Director of the Cancer Center, Rudolfina-Spitals in Vienna, and his assistant Gisa Kaminer study nutrition against cancer.  When they mixed cancer cells with blood from healthy patients in a test tube, the cancer cells were destroyed.  When they mixed cancer cells with the blood from cancer-sick patients, the cancer cells survived. This led them to believe that the blood of cancer-sick individuals contains an inhibiting element that prevents the immune system’s cells to attack cancer cells.

1938

Max Wolf took Freund and Kaminer’s research further and tried to determine the elements that were contained in the blood of healthy patients but absent in the blood of cancer patients.  He suspected that the element is an enzyme and so he carried out numerous tests.

1941

Adolf Gaschler studied the effect of enzyme therapy on malign tumors and chronic inflammation at the Berliner Charite.  In 1955, he published the results, and explained how trypsin enzyme can be used for treating tumors.

1944

Max Wolf became the Director of the Biological Research Institute of Columbia University, where he continued his research on enzyme in medicine.  Along with scientist Helene Benitez, Max Wolf carried out thousands of tests in order to isolate and purify enzymes extracted from plant and animal organisms.  They developed two exceptionally active enzyme combinations that they called “Wolf-Benitez-Enzyme combinations”.  One combination was for treating inflammations and the other for degenerative diseases.  The name “Wolf-Benitez-Enzyme combinations” was later shortened to “Wobenzym”.

1950

Max Wolf produced his own enzyme combinations in his laboratory but they were not for sale on the market. Using which he treated the American “high society”.

1959

Karl Ransberger, CEO of the Munich enterprise Mucos, an emulsion producer, met Max Wolf in New York and became convinced of the effectiveness of Wolf’s therapy concept.  In the meantime, Wolf contracted an Austrian firm for the production of WoBe-enzymes, to make the products more economical and more available to the population.  The enzyme combination WoBe was registered in Spain in 1959 and in Germany in 1960 as a pharmaceutical product.

1963

The enzyme combination developed by Wolf and Benitez, the WoBe-enzyme combination (later called Wobe Mucos E) was approved as medication in Germany under the direction of Karl Ransberger.  It was used systemically as well as locally and was approved for the treatment of cancer and metastasis prophylaxis.

1965 to Today

Enzymes are proven effective in the treatment of inflammation, edema, rheumatism, herpes zoster, sinusitis and injuries, as well as to assist post-surgery healing. They are also effective in regulating the immune system and blood flow.  Enzymes are proven to be effective and easy to digest.  The enzyme combination WOBE-MUCOS E, researched by Karl Ransberger is used as complementary therapy in cancer treatments and chemo- and radiation therapy, as well as against metastasis prophylaxis.  Enzyme therapy becomes an essential support to cancer treatment. 

WOBE-MUCOS E was taken off the market according to legal formalities in September 2005.  Since Wobe-Mucos E had demonstrated its medicinal value and had not been taken off the shelves for reasons of quality or effectiveness, when it was removed from the market, the enzyme product supplies for the treatment of cancer were greatly missed. Nonetheless, in December 2000, a nutraceutical (nutrition supplement) with similar immune-system supportive characteristics was put on the market; it was called Wobe-Mucos NEM.

A research team at the Institute for Biochemistry at the University of Leipzig, lead by Professor Gerd Birkenmeier, is currently studying the therapeutic and prophylactic use of enzymes in modern medicine.

Need

Enzymes are very important and are needed for the proper functioning of the body. Though enzymes are needed in various fields of life but in the following is the major need of enzymes in the aspect of medicine.

Essential Role in Healthy Digestion

Enzymes are protein-based substances that play an essential role in every function in the human body, including eating, digestion, breathing, kidney and liver function, reproduction and elimination. In the digestive tract enzymes break down foods by breaking apart the bonds that hold nutrients together—nutrients that the body will eventually use for energy.

Several locations in the digestive system secrete enzymes: the mouth, stomach, pancreas and cells of the small intestine. Proteins, fats and carbohydrates are the most basic foods that the body breaks down and absorbs, and the enzymes protease, lipase and amylase, respectively, are made by the body for this purpose. A healthy diet, exercise and proper detoxification will help promote healthy enzyme production in the body.

In addition to the enzymes and secretions made by the body, raw, unprocessed foods also contain enzymes that assist with digestion. However, due to modern food production methods, many foods are depleted of their natural enzymes through cooking and processing.

As a result, many experts encourage the consumption of fresh, whole and unprocessed foods to offset the common effects of the modern diet on digestion.

Cellulase & Phytase

Additionally, there are several enzymes that the human body lacks, such as cellulase, (the enzyme that breaks down cellulose), and phytase, the enzyme that breaks down the phytates and phytic acid we consume in our diet. Because of this deficiency, many people have difficulty breaking down certain foods such as starchy beans, legumes and nuts. Without the essential enzymes needed for proper digestion, the body may not completely break down those foods to absorb their nutrients. As a result, undigested food in the digestive tract can ferment, causing gas, bloating and other digestive difficulties.

Advantages and applications

Enzymes are used in medicine because of their catalytic abilities, which ensure that throughout any reaction they will remain unchanged. They are useful because they are specific, and so avoid side effects when used on a patient. Use of enzymes in medicine is highly ethical, socially desirable and beneficial, economically efficient and represents an advance in modern technological processes.

Analytical tests

Diabetics use strips of paper impregnated with glucose oxidase to monitor their blood sugar. 

Therapeutic enzymes

Enzymes are sometimes used as medicines to replace enzyme deficiencies in patients like is the use of blood clotting factors to treat hemophilia, or the opposite where proteases are used to degrade fibrin; to prevent the formation of dangerous blood clots. Nuclease is a possible therapy for cystic fibrosis, but it is not clear how commercialized and therapeutically successful this has been. 

Drug manufacture

The chemical synthesis of complex drugs is often difficult and companies turn to enzymes to perform chemical conversions.

In a semi-therapeutic way

Enzymes are used to aid digestion, to supplement the natural amylase, lipase and protease produced by the pancreas. People with lactose intolerance lose the enzyme lactase. Lactase supplements help to avoid stomach upsets for these people. 

Wounds cleaning

Proteases are used to clean wounds and therefore accelerate the healing process. 

Diagnostic purpose

The presence of enzymes where they should not be present can also help to diagnose disease. For example, when the liver is diseased or damaged, enzymes leak into the bloodstream. Testing the blood for these enzymes can confirm liver damage.

Enzyme therapy

Enzymes are sometimes used in mainstream medicine. For example, the approved chemotherapy drug asparaginase is an enzyme. Some enzymes are also used for other serious illnesses. Pancreatic enzymes may be given to treat digestive problems resulting from removal of the pancreas or certain diseases of the pancreas.

However, some alternative medicine practitioners claim that digestive enzyme supplements not only relieve digestive problems, such as ulcers and food allergies, but also strengthen the immune system, improve circulation, ease sore throat pain, aid weight loss, and relieve hay fever, ulcers, and rheumatoid arthritis. Proponents also claim that certain enzymes remove a protective coating from cancer cells, allowing white blood cells to identify and attack them (Figure 2).

Enzyme therapy/ Enzymes in medicine.
Figure 2. Enzyme therapy/ Enzymes in medicine.

Synthesis

The starting point for enzyme production is a vial of a selected strain of microorganisms. They will be nurtured and fed until they multiply many thousand times. Then the desired end-product is recovered from the fermentation broth and sold as a standardized product.

A single bacteria or fungus is able to produce only a very small portion of the enzyme, but billions microorganisms, however, can produce large amounts of enzyme. The process of multiplying microorganisms by millions is called fermentation.

One very important aspect of fermentation is sterilization. In order to cultivate a particular production strain, it is first necessary to eliminate all the native microorganisms present in the raw materials and equipment. If proper sterilization is not done, other wild organisms will quickly outnumber the production strain and no production will occur.

The production strain is first cultivated in a small flask containing nutrients. The flask is placed in an incubator, which provides the optimal temperature for the microorganism cells to germinate. Once the flask is ready, the cells are transferred to a seed fermenter, which is a large tank, containing previously sterilized raw materials and water is known as the medium. Seed fermentation allows the cells to reproduce and adapt to the environment and nutrients that will be encountered later on.

After the seed fermentation, the cells are transferred to a larger tank- the main fermenter, where fermentation time, temperature, pH and air are controlled to optimize growth. When this fermentation is complete, the mixture of cells, nutrients and enzymes, called the broth, is ready for filtration and purification (Figure 3).

Filtration and purification, termed as downstream processing, is done after enzyme fermentation. The enzymes are extracted from the fermentation broth by various chemical treatments to ensure efficient extraction, followed by removal of the broth using either centrifugation or filtration. Followed by a series of other filtration processes, the enzymes are finally separated from the water using an evaporation process.

After this the enzymes are formulated and standardized in form of powder, liquid or granules.

Enzyme Synthesis
Figure 3. Enzyme Synthesis

Conclusion

Enzymes today are used for various purposes in medicine. In the 20th century the use of enzymes in pharmaceutical and industry is limited to a low number of very successful applications. However it is the very success of such applications that continues to help pave the way for new developments and it is clear that there is no shortage of ideas. After having an insight to the application of enzymes in the medical and pharmaceutical problems it can be realized that it is an exciting and promising field that is ripe for development in the near future.

References

  • Bayliss W. M., 1919. The nature of enzyme action. London: Longmans, Green and co. 39 Paternoster Row.
  • Cichoke A. J., 1999. The complete book of enzyme therapy. New York: Penguin. ISBN: 0895298171.
  • Cohnheim O., 1910. Enzymes. New York: John Willey and sons.
  • Retrieved at 19th of January 2014, from; http://www.h2g2.com/
  • Samejima H., Kimura K., Ado Y., 1980. Recent development and future directions of enzyme technology in Japan. Biochimie, Volume 62(5-6)., pp; 299–315. doi: 10.1016
  • Shanmugam T., Sathishkumar T., 2009. Enzyme Technology. New Delhi: I. K. International publication house Pvt. Ltd. ISBN: 978-93-80026-05-3.

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