Chemotherapy and drug design - Essay Example

Chemotherapy and drug design Introduction Iron is the most common micronutrient in many organisms and serves in many vital functions in the body. It occurs in very small quantities in the human body and even lesser amounts are used by it. On average, an adult has almost 4 grams of iron. The distinctive feature of iron from other minerals and elements in the human body is that, there is no formal way of excretion of excess iron from the body. Although it occurs in small quantities in the human body, it plays critical roles in our health.

It has to be in the right quantity in the human body, because its increase or decrease can cause serious health implications (Ferreira, Moura and Franco, 1999). In biological systems, it occurs in three oxidation states which are; the ferrous state (Fe 2+), ferric state (Fe 3+) and Ferryl form (Fe 4+).The ferryl species are created during catalytic cycle of various enzymes such as cytochrome P450, monooxygenase and ribonucleotide reductase. There is no evidence that ferryl form participates in iron storage or transport (Iron Homeostasis, Heme and porphyrin synthesis and metabolism, n.d). The redox potential of Fe 3+ /Fe 2+ is important in many biological processes such as DNA synthesis, respiration and oxygen transport.

The value of iron relies on its incorporation in mettaloenzymes such as mononuclear, dinuclear, polynuclear complex and porphyrin. Iron has a higher affinity for electronegative atoms such as sulfur, nitrogen and oxygen and due to this reason, these electronegative atoms occurs at the centre of macromolecule (Iron Homeostasis, Heme and porphyrin synthesis and metabolism, n.d).Under acidic conditions, iron occurs in Fe 2+ state while in neutral or alkaline conditions, Fe 3+ occurs. In Fe 3+, iron forms large complexes with water, peroxidates and anions.

Such complexes have low solubility and when they aggregate they cause pathological effects. Moreover, iron can bind to various macromolecules and consequently interfere with their structure and function. The body has many iron binding proteins which protects it against the harmful effects of iron. Iron is consumed in the diet either in the form of heme iron or free iron. In the intestines, it is reduced to ferrous state from ferric form. It is then transported into the cells via a divalent metal transporter (DMT1).

Uptake of iron hem in the intestines occurs through the interaction of heme carrier protein and the dietary heme. Heme oxygenate catalyzes the release of iron from the heme. Within the intestinal enterocytes, iron is stored in the state bound to ferritin. Transporter protein ferroportion which is also called (IREG 1) catalyzes the transport of iron across basolateral membrane of intestinal enterocytes to the circulation. Hephaestin is a copper containing ferroxidase enzyme which is associated with ferroportion and it oxidizes ferrous iron to ferric form.

Ferric iron is bound to transferrin and is stored in the hepatocytes. Liver is the main organ of iron storage while the bone marrow is the main organ for iron utilization ie heme synthesis (Iron Homeostasis, Heme and porphyrin synthesis and metabolism, n.d).Iron deficiency is more likely to occur in women than in men because of menstruation, pregnancy and lactation. This is why women are normally recommended iron rich diet to compensate for the loss. A high quantity of iron than the normal levels leads to hemochromatosis while its deficiency causes anemia.

Men are also vulnerable to these health conditions due to iron but these instances are relatively less in number as compared to women (Crichton and Boelaert, 2001).Iron; its role in the bodyLike all matter in the world, the human body is also made of various elements and chemical substances combined together to form a single combined unit that works in coordination with each other. The human body contains iron as an essential element that helps many chemical processes to take place in it. Iron is the central atom in heme group that are a part of hemoprotiens.

These hemoprotiens have three vital functions to perform in the blood, first as oxygen carriers, secondly to act as activators of molecular oxygen and thirdly as proteins that transfer electrons throughout the body. As oxygen carriers, one of the most vital functions iron performs as a part of hemoprotiens is that it takes oxygen molecules throughout the body through the lungs via hemoglobin, myoglobin and neuroglobin. Hemoglobin is a vital element of red blood cells that gives blood its red pigment.

Myoglobin is an iron containing and oxygen binding protein that found as an essential element of tissues and muscles. Neuroglobin proteins take the oxygen to the brain and throughout the nervous system (Crichton, 2009). Apart from being a metalloprotein, iron is required in production of many enzymes in the human body including Hydroxylases, a-Ketoacid-dependent Enzymes, Isopenicillin N Synthase and diiron Proteins. Iron is a vital part of the DNA synthesis process and cell division in the body.

It also assists to reduce the effect of free radicals in the body. Due to its importance in the body, our bodies have a mechanism that recycles it for reuse. The bacteria inside the human body also require iron for their metabolic processes. In case of bacterial infection in the human body, the iron inside the human body is withheld by transferrin, which improves the immunity of the human body against health depreciation.Types of iron that a body takes and its absorptionMost of the iron that is required by the human body is recycled from the reticuloendothelial system and reused in the body.

Not all of the iron that is consumed in the diet is absorbed by the body. Only a small percentage of the consumed amount is absorbed depending on the body requirements. Iron deficiency occurs when there is a higher demand for iron in the body which the diet cannot meet, through blood loss, nutritional deficiencies and inflammations of intestinal lining which can cause reduced release of iron from enterocytes. Iron can be obtained from food sources, animal meat and plants. The iron form animal meat is called the heme iron and the iron that is attained from the plants is the non-heme iron or ferrous and ferric iron.

It depends on the diet the person is taking that determines what percentage of different types of iron is being taken by the human body. In a normal omnivore diet, most part of the iron that is taken in is from plants that are the ferric and ferrous iron and heme iron is relatively less in quantity. However, out of the two types of iron that is available in the food, the body prefers to consume heme iron to the non-heme iron because of the readiness of heme-iron to be absorbed in the human body (Crichton and Boelaert, 2001).

The rate of absorption of iron in the human body also changes with the requirement of iron in the body and the food intake. The foods containing higher amounts of phytates, phosphates, fiber and oxalates reduces the absorption of iron form plant oriented meals. Soil clay, tannins, iron overload in the body and antacid medication also inhibit the absorption of iron in the body. To increase the amount of iron absorption from plants, vitamin C is added to the meals. Vitamin C changes the electron charge on ferric and ferrous iron coming from plant and thus increases its absorption in the human body.

Citrus fruits, red and green pepper, sugars, alcohol, green leafy vegetables help to increase iron absorption. Taking of tea and coffee after meals has been shown to reduce the absorption of iron (Templeton, 2002). The major contributor of iron for the human body is the fleshy foods that we consume such as kidney beans, dried fruits, wholegrain cereals, leafy vegetables and dairy products. For infants, breast milk provides them with the iron requirements. If the mother cannot breast feed her baby, goat milk is recommended as it is close to mother’s milk infant formula.

Cow’s milk is not recommended as it can lead to serious complication to the babies if they are fed before they attain the age of one year. When iron rich products are cooked, most of the iron is lost due to chemical reaction that take place as a result of high temperatures. Iron cooking-wares that are able to preserve the quantity of iron in the food have been developed, but in some cases may also lead to iron toxicity.Blood transfusion can also be used to replenish iron deficiency in the body.

In certain medical conditions when the blood lacks necessary iron because the body is not able to absorb enough iron, the doctors recommend blood transfusion. Iron supplements are also used to provide iron in the body but they should not be over-consumed to avoid iron intoxication.Iron metabolism, transport, and excretion in the human bodyHomeostasis is known as the equilibrium position of the human body. The human body is an amazing system of inter related parts that tries to maintain a balance in each and every aspect.

The homeostatic state of the body is maintained by the metabolism and catabolism processes that takes place in the body. The main role in the maintenance of this homeostasis is played by the absorption, metabolism and excretion stages in the body (Crichton, 2009). Iron is one of the fundamental elements that are present in the human body and nearly 60% of all iron is present in the hemoglobin. Apart from recycling the iron that is already present in the body, the main source of iron is the diet intake.

In the stomach, the iron is kept soluble with the help of gastric acid, intestinal mucous and other components like ascorbic acid. The absorption of iron primarily takes place in the duodenum and upper jejunum. The iron then passes though the mucus cells and enters the body circulation system. The mucus cell act as the gateways to the body and iron molecules are transferred to the transferrin molecules that are responsible for the transportation of iron molecules inside the body. Transferrins are glycoprotein which are produced by the liver and secreted into the plasma to carry iron.

A single transferrin molecule can carry two molecules of iron. At any normal biological condition, only 30% of the transferrin molecules have iron on them. This leaves extra space for iron to be carried when required by the body. Transferrin takes some of the iron to bone marrow and other blood forming tissues to help in the production of blood through a process called erythrogenesis, while the remaining iron is changed into ions and is transported to the liver. In the liver, iron is stored by ferritin in the hepatocytes.

Hepatocytes are a type of liver cells that make almost 70% of the cytoplasmic mass of the liver. Ferritin is a type of protein that controls the flow and storage of iron in the liver (Ferreira, Moura and Franco, 1999).As most of the iron that is consumed by the human body is not all absorbed, the iron that is already in the body is reused for the function of the body that makes a complete iron cycle. The iron is again transferred to transferrin during the catabolism in the human body, which again transports the iron to the required locations.

Through this, way the body keeps a balance of iron that is required. Evolution is an ongoing process and it is firmly believed that what man is today is entirely unlike what he was a million years ago. He has evolved into perfect masterpiece of nature that has adopted changes over time. Still, when it comes to iron, there is nothing precious than this mineral to human body. It can also be said that because of its preciousness to the human body, even after years of evolution, the body has no physiological means to excrete excessive iron from the body.

It will still be wrong to say that the body does not lose iron in any way. Almost 1mg of iron is lost every day through sloughing of the skin and other mucosal cells, biological actions like urination and sweating and also through bleeding. The loss of iron increases in women during menstruation cycle, pregnancy and breastfeeding the child (Templeton, 2002). The effects of lower iron level in the bodyIron deficiency makes one of the most common problems in women especially in adolescent girls.

The deficiency of iron can cause serious implication for the body and can even lead to death. Anemia is a common problem that is related to iron deficiency in the human body. When iron is less than the required level in the body, the body is not able to produce enough blood and therefore it cannot meet the needs of the body such as ensuring good flow of oxygen to the body tissues and muscles (Earl, Woteki and Calloway, 1993).Reduction of iron in the body leads to anemia. Iron constitutes an integral part of the red blood cells that carries oxygen and other important nutrients to different parts of the body.

The body uses iron that is obtained through diet and recycling. Although the body can maintain a level of homeostasis when there is an urgent need of iron, this does not happen all the times as at times it is not able to maintain the required level of iron. There are a number of reasons that can lead to reduction of iron from the body and lead to iron deficiency anemia (Lauffer, 1992).One of the most common causes of iron deficiency is the excessive loss of blood. Iron is an important part of blood and with the loss of blood from the body; iron is lost with it.

Women have regular menstruation cycles and pregnancy durations. During these durations, the iron level falls dramatically in the body and if iron rich diet or iron supplements are not taken, this can lead to anemia. If the body needs more iron and the diet that is being taken is rich in iron, the body starts absorbing more iron than it regularly does but if the diet a person is taking is less in iron or contains mostly non-heme iron, serious medical implications may arise for the body. Another cause of iron deficiency in the body is due to impaired metabolic functions of the body.

If the body is not able to absorb enough iron that is required either due to inflammation of intestinal lining, this can lead to iron deficiency. Going strictly vegetarian can also lead to reduction of iron level from the body. Plants contain ferric and ferrous iron ions that are not readily absorbed by the body during digestion process. The body prefers to absorb heme iron that is achieved from the flesh of animals because of its readiness to perform vital functions in the body. If vitamin C is added to the diet containing non-heme iron, the body starts absorbing this iron together with heme iron.

Iron deficiency anemia needs to be analyzed first with blood tests before the person is declared anemic. However, there are a few symptoms that indicate the presence of anemia. The symptoms of anemia are mild in the start and develop severer over time. Some of the initial symptoms of blood deficiency anemia include feeling irritated even over non-issues, lack of concentration, feeling tired and unnecessary fatigue in the body and regular headaches. If iron deficiency anemia carries on with time, it can lead to the whites of the eye getting bluish, pale skin, breathlessness and feeling of suffocation, severe headaches, brittle nails, feeling of heart racing and hair loss.

People with other medical conditions may also have bloody stools, heavy menstruation in women and regular weight loss (Lauffer, 1992). Complete blood cell count test is carried out as a primary test in case iron deficiency anemia is diagnosed by the doctor from the patient’s symptoms, The complete blood cell count test gives the exact red blood cell count, white blood cells count, platelets count, hematocrit, hemoglobin and differential blood count. There are other tests that can be carried out to check iron levels in the body.

Such tests are serum ferritin and serum iron tests, iron binding capacity and bone marrow test. The treatment of iron deficiency anemia usually takes 2-3 months for initial revival of health but the proper treatment can go up to the duration of 6-8 months. After the cause of iron deficiency anemia is discovered, the doctors normally prescribe iron supplements and advise iron rich nutrition. Iron supplements contain ferrous sulfate and they help in building up iron stocks in the body which is mostly stored in the bone marrow and the liver.

Iron supplements are either oral or intravenous and they are prescribed depending on the condition of the patient. Iron deficiency anemia in the initial stages can be rectified with just change in the dietary patterns. Meat (especially liver), egg yolk, soybeans, dried lentils, peas and whole gain bread are rich in iron and can easily solve iron deficiency. These foods can also be taken along side with iron supplements in case of severe anemia. The effects of higher iron level in the human bodyLike the reduction of iron from the body, excess iron in the body can damage liver, heart, and other metabolically active organs or tissues.

These damages range from liver cirrhosis culminating to death. Excess presence of iron in the body is called hemochromatosis. There are two major reasons of hemochromatosis or iron over load to occur in the body. It can be hereditary or occur due to dietary intake that is rich in iron contents. Hemochromatosis is very common in European Caucasians and North American people and mostly in men as compared to women. In almost every 250-300 individuals in these regions, there is one carrier of hemochromatosis problem.

This also leads to genetically transfer of the disorder into the off springs. Hemochromatosis is also a common problem with people having blood related disorders like thalassemia that requires the patient to undergo blood transfusion often. Hemochromatosis also occurs among people having sideroblastic anemia, hemolytic anemia and chronic alcohol problems (Lauffer, 1992). People with hemochromatosis absorb three to four folds more iron than a normal person. The excess iron accumulates in the body eventually causing a serious health effects.

It can harm any body organ to the extent of causing organ failure and consequently death of the person if it not treated. A normal person has almost 4-6 grams of iron in the body, however a person with hemochromatosis can have 15 to 50 grams or even more iron in their bodies. Because the blood can not consume the excess iron, the iron that is not used is stored in various organs. Excess iron reacts with other free radicals and harms the organs where they are stored. The primary organ that bears the harm is the liver because it acts as the major store house of excessive iron.

In the initial stages, the liver enlarges due to over stuffing and inflammation. In later stages, liver scarring and hemorrhaging occurs. In even severe cases, this can lead to hepatitis A and C, liver cirrhosis and even cancer. Other organs such as pancrease and the heart are also affected due to hemochromatosis. Excess iron in the body has also been shown to cause memory loss, unexpected mood swings and loss of sexual desire and even loss of hair. There are several warning symptoms which can indicate danger of iron toxicity.

Some of the common symptoms include unnecessary fatigue, loss of energy, loss of body hair and sexual desire. The patient with high iron levels will develop a darker skin tone and will complain of mild to severe abdominal pain. Other symptoms are loss of weight and abrupt sense of weakness in the body (Rockey, 2002) There are several blood and other organ related tests that can be used to determine the severity of hemochromatosis in the human body. Four of the most basic tests are serum ferritin, serum iron, pre-liver biopsy test and the test to check the percentage of transferrin saturation in the body.

There are some other tests as well which help determine the health of the organs of the body. If this iron disorder does not occur due to blood transfusion or other related physical disorders, then the doctors can recommend a genetic test to determine the genetic basis of the disease (Rockey, 2002). Hemochromatosis is a serious blood disorder and early diagnosis is important for the survival of the patient. One of the primary steps towards the treatment of this health condition is taking iron free diets.

This method has been one of the most successful treatments for this disorder. Blood transfusion has also been effective in managing this condition.When the blood is removed from the body, the body produces more blood which absorbs the iron from iron stores and therefore helping in reduction of iron from the body. In any blood removal session, almost 500MLs of blood is removed from the body. Families with a history of hemochromatosis such as Caucasian and Americas should go through blood tests to test iron levels and start early treatment if this health condition is discovered (Lee, n.d).ConclusionIron is one of the most amazing elements that are present in the human body.

On average adult body requires almost 4 grams of iron which can vary according to body needs. Without iron, the blood cannot carry oxygen throughout the body leading to gradual death. However, it is very important that iron be in the right quantity in the body because excess or less quantity of iron can create serious health implications for the body. ReferencesCrichton, R.R and Boelaert, J.R. (2001). Inorganic Biochemistry of Iron Metabolism. New York : E. Horwood,Ferreira G.C., Moura, J.G and Franco, R. (1999). Iron Metabolism; Inorganic Biochemistry and Regulatory Mechanisms, Weinheim; New York: Wiley-VCH.

Iron Homeostasis, Heme and porphyrin synthesis and metabolism, Available at: http://thermedical biochemistrypage.org/heme-porpyrin.html/. Accessed on 10 Jan. 2012.Lauffer, R.B. (1992). Iron and Human Disease. CRC PressMedeiros Robert E. C. Wildman. (2011) Advanced Human Nutrition. Jones & Bartlett Publishers.MedicineNet, Dennis Lee, MD, Hereditary Hemochromatosis (Iron Overload).Available at: http://www.medicinenet.com/iron_overload/. Accessed 25 Oct. 2011.National Center for Biotechnology Information, U.S. National Library of Medicine, April 12, 2010.

Available at:http://www.ncbi.nlm.nih. gov/pubmedhealth/PMH0001368 /. Accessed on 25 Oct. 2011.Přemysl Poňka Herbert M. Schulman Robert C. Woodworth (1990). Iron Transport and Storage. CRC PressReddy, K.H. (2007). Bioinorganic Chemistry. New Age InternationalRobert O Earl; Catherine E Woteki; Doris Howes Calloway. (1993) Iron deficiency anemia: recommended guidelines for the prevention, detection, and management among U.S. children and women of childbearing age. Washington, DC : National Academy PressRobert R.

Crichton (2009) Iron Metabolism. Chichester, UK : John Wiley & SonsRockey, D.C. (2002). Hemochromatosis, Seminars in gastrointestinal disease, v.13, issue2. Philadelphia, PA: W.B. SaundersTempleton, D.M. (2002), Molecular and Cellular Iron Transport. New York: Marcel Dekker