What is Erythropoietin?
Erythropoietin (EPO) is a glycoprotein hormone that controls erythopoiesis, the production of red blood cells. It also has other known biological functions; erythropoietin plays an important role in the brain's response to neuronal injury.EPO is also involved in the wound healing process. It is a cytokine for red blood cell precursors in the bone marrow._
It is produced by interstitial fibroblasts in the kidney in close association with peritubular capillary and tubular epithelial cells. It is also produced in perisinusoidal Ito cells in the liver. Erythropoietin is produced at a lesser extent by the liver. Approximately about 10% of erythropoietin is produced in the liver and the other 90% in the kidneys. The erythropoietin gene has been found on human chromosome 7 (in band 7q21). The different DNA around erythropoietin gene act to control the production of erythropoietin from the liver and of the kidney.
Kidney cells that make erythropoietin is specialized so that they are sensitive to the oxygen levels in the blood that flows through the kidneys. These cells make and release erythropoietin when oxygen levels are too low. Low oxygen levels in the kidney may indicate anemia, a number of red blood cells are reduced, or molecules of hemoglobin that carries oxygen throughout the body.
It is produced by interstitial fibroblasts in the kidney in close association with peritubular capillary and tubular epithelial cells. It is also produced in perisinusoidal Ito cells in the liver. Erythropoietin is produced at a lesser extent by the liver. Approximately about 10% of erythropoietin is produced in the liver and the other 90% in the kidneys. The erythropoietin gene has been found on human chromosome 7 (in band 7q21). The different DNA around erythropoietin gene act to control the production of erythropoietin from the liver and of the kidney.
Kidney cells that make erythropoietin is specialized so that they are sensitive to the oxygen levels in the blood that flows through the kidneys. These cells make and release erythropoietin when oxygen levels are too low. Low oxygen levels in the kidney may indicate anemia, a number of red blood cells are reduced, or molecules of hemoglobin that carries oxygen throughout the body.
Erythropoietin as the drug
_ Using recombinant DNA technology, erythropoietin has been produced
synthetically to use as a treatment for certain types of
anemia. Erythropoietin can be used to fix anemia by stimulating
red blood cell production in bone marrow.The
medicine is known as epoetin alfa (Epogen, Procrit). It can be given as
an injection intravenously (in the vein) or subcutaneously (under the skin).
Epoetin alfa (Epogen, Procrit)] is used in many installation-fitting clinic. The most common use is in people with anemia associated with abnormal function of the kidney. When the kidneys are not functioning properly, they produce less than normal amounts of erythropoietin, which can lead to the production of red blood cells being low, or anemia. Therefore, by replacing erythropoietin with an injection of synthetic erythropoietin, anemia associated with kidney disease may be treated. Today, Epogen or Procrit is a standard part of therapy in patients with kidney disease who require dialysis to both treat and prevent anemia.Other uses of erythropoietin may include treatment of anemia associated with AZT treatment (used to treat AIDS) and cancer-related anemia. EPO has been shown to also help certain neurological diseases, like schizophrenia. Research has also suggested that EPO improves the survival rate for children suffering from cerebral malaria; which is caused by malaria parasite's blocking blood vessels in the brain. Epo has also been used by athletes, most notoriously in the Tour De France bicycle racers, to increase their endurance. In addition, recent studies have suggested that overuse of the drug can harm patients. Sales of this drug, as a result, have declined over the last few years.
Epoetin alfa (Epogen, Procrit)] is used in many installation-fitting clinic. The most common use is in people with anemia associated with abnormal function of the kidney. When the kidneys are not functioning properly, they produce less than normal amounts of erythropoietin, which can lead to the production of red blood cells being low, or anemia. Therefore, by replacing erythropoietin with an injection of synthetic erythropoietin, anemia associated with kidney disease may be treated. Today, Epogen or Procrit is a standard part of therapy in patients with kidney disease who require dialysis to both treat and prevent anemia.Other uses of erythropoietin may include treatment of anemia associated with AZT treatment (used to treat AIDS) and cancer-related anemia. EPO has been shown to also help certain neurological diseases, like schizophrenia. Research has also suggested that EPO improves the survival rate for children suffering from cerebral malaria; which is caused by malaria parasite's blocking blood vessels in the brain. Epo has also been used by athletes, most notoriously in the Tour De France bicycle racers, to increase their endurance. In addition, recent studies have suggested that overuse of the drug can harm patients. Sales of this drug, as a result, have declined over the last few years.
Discovery of Erythropoietin
_ In the late 1970s, Dr. Goldwasser, working at the University of Chicago, isolated and purified erythropoietin aka Epo. He then shared his findings with a young biotechnology company,
which figured out how to produce larger amounts of the protein using
genetic engineering.
That company, Amgen,
became the world’s biggest biotechnology company on the basis of Epo.
Sales of erythropoietin under names like Epogen, Procrit and Aranesp amounted
to billions of dollars a year for Amgen, as well as Johnson & Johnson and Roche.
Most people undergoing kidney dialysis now receive Epo, helping to relieve them of severe anemia, which can sap them of energy. Many cancer patients also get the drug to combat anemia caused by chemotherapy.
While Epo created huge profits for drug companies, Dr. Goldwasser won neither fame nor fortune. Although he notified his university about his accomplishment, it never patented Epo, and Dr. Goldwasser did not follow up. Years after this he told a university publicist “One percent of one percent of the drug’s annual revenues would have funded my lab quite handsomely.”
As far back as 1906, two French researchers had postulated the existence of a substance that prompts the production of red blood cells, which carry oxygen to the body’s tissues. But if that substance did exist, it was in such minuscule quantities that no one could find it.
Dr. Goldwasser began to look for it in 1955 at the urging of his mentor, the noted hematologist Leon O. Jacobson. Originally he had thought it would take only several months to accomplish this, but instead it took 20 years. In 1957, Dr. Goldwasser and colleagues found out that Epo was made in the kidneys by systematically removing different organs from rats to see if they became anemic. That helped explain why patients with kidney failure became anemic. He figured that animals with anemia would produce more Epo, making finding the protein much easier to find. Dr. Goldwasser then spent years visiting a slaughterhouse outside Chicago, there he would inject sheep with a chemical that would make them anemic. Afterwards he would collect the blood and try to separate out the various components to find erythropoietin.
It ended up easier to find Epo in urine than in blood. In 1973, when his search seemed to be going nowhere, Dr. Goldwasser received a letter from Takaji Miyake of Kumamoto University in Japan. Takaji Miyake had been collecting urine from people with a disease called aplastic anemia. At the end of 1975, Dr. Miyake and Dr. Goldwasser met at Palmer House hotel in Chicago. Dr. Miyake gave Dr. Golwasser a foot-square package wrapped in brightly colored silk, inside was the dried concentrate of 2,550 liters, or about 674 gallons, of urine. From that material Dr. Goldwasser and his assistant Charles Kung and Dr. Miyake were able to purify 8 milligrams, about 3 ten-thousandths of an ounce, of Epo. Just enough to fill a small vial. They then published a paper in 1977. This difficult process of extraction was not practical for producing enough Epo to use as a drug, but the age of gene splicing was dawning. Getting some of the protein’s composition from Dr. Golwasser, Fu-Kuen Lin, a scientist at Amgen, was eventually able to clone the human gene for Epo. The gene was spliced into hamster cells, which churned out enough Epo to sell as a drug.
This drug was first tested by patients undergoing dialysis, who suffered debilitating anemia. The only treatment at that time, before Epo, was frequent blood transfusions. Dr. John W. Adamson conducted the first trial around 1985 while at the University of Washington. Patients who before had so little energy they could barely walk were now fully functional, Dr. Adamson said. Nowadays, thanks to Epo, patients with such a horrible anemic dialysis have dissapeared accoridng to Dr. Adamson, who is now at the University of California, San Diego.
Most people undergoing kidney dialysis now receive Epo, helping to relieve them of severe anemia, which can sap them of energy. Many cancer patients also get the drug to combat anemia caused by chemotherapy.
While Epo created huge profits for drug companies, Dr. Goldwasser won neither fame nor fortune. Although he notified his university about his accomplishment, it never patented Epo, and Dr. Goldwasser did not follow up. Years after this he told a university publicist “One percent of one percent of the drug’s annual revenues would have funded my lab quite handsomely.”
As far back as 1906, two French researchers had postulated the existence of a substance that prompts the production of red blood cells, which carry oxygen to the body’s tissues. But if that substance did exist, it was in such minuscule quantities that no one could find it.
Dr. Goldwasser began to look for it in 1955 at the urging of his mentor, the noted hematologist Leon O. Jacobson. Originally he had thought it would take only several months to accomplish this, but instead it took 20 years. In 1957, Dr. Goldwasser and colleagues found out that Epo was made in the kidneys by systematically removing different organs from rats to see if they became anemic. That helped explain why patients with kidney failure became anemic. He figured that animals with anemia would produce more Epo, making finding the protein much easier to find. Dr. Goldwasser then spent years visiting a slaughterhouse outside Chicago, there he would inject sheep with a chemical that would make them anemic. Afterwards he would collect the blood and try to separate out the various components to find erythropoietin.
It ended up easier to find Epo in urine than in blood. In 1973, when his search seemed to be going nowhere, Dr. Goldwasser received a letter from Takaji Miyake of Kumamoto University in Japan. Takaji Miyake had been collecting urine from people with a disease called aplastic anemia. At the end of 1975, Dr. Miyake and Dr. Goldwasser met at Palmer House hotel in Chicago. Dr. Miyake gave Dr. Golwasser a foot-square package wrapped in brightly colored silk, inside was the dried concentrate of 2,550 liters, or about 674 gallons, of urine. From that material Dr. Goldwasser and his assistant Charles Kung and Dr. Miyake were able to purify 8 milligrams, about 3 ten-thousandths of an ounce, of Epo. Just enough to fill a small vial. They then published a paper in 1977. This difficult process of extraction was not practical for producing enough Epo to use as a drug, but the age of gene splicing was dawning. Getting some of the protein’s composition from Dr. Golwasser, Fu-Kuen Lin, a scientist at Amgen, was eventually able to clone the human gene for Epo. The gene was spliced into hamster cells, which churned out enough Epo to sell as a drug.
This drug was first tested by patients undergoing dialysis, who suffered debilitating anemia. The only treatment at that time, before Epo, was frequent blood transfusions. Dr. John W. Adamson conducted the first trial around 1985 while at the University of Washington. Patients who before had so little energy they could barely walk were now fully functional, Dr. Adamson said. Nowadays, thanks to Epo, patients with such a horrible anemic dialysis have dissapeared accoridng to Dr. Adamson, who is now at the University of California, San Diego.
Chemistry Quick Facts
The chemical formula of Erythropoietin is C815H1317N233O241S5
Melting point of 53 ˚C
Molecular weight 18396 g/mol__
Melting point of 53 ˚C
Molecular weight 18396 g/mol__
Chemical Structure
_Erythrpoietin is made up of a four-membered alpha-helical bundle with connecting loops
Although its nucleotide and amino acid sequences are known by scientists, its tertiary structure remains elusive. Antipeptide antibody and mutagenesis studies have increased the ability to be able to study structure/function and certain spatial relationships.
Although its nucleotide and amino acid sequences are known by scientists, its tertiary structure remains elusive. Antipeptide antibody and mutagenesis studies have increased the ability to be able to study structure/function and certain spatial relationships.
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