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Cholesterol Metabolism and Transport and diseases and treatments

Page history last edited by Kristen Koonce 14 years, 11 months ago

 

 

Cholesterol, Metabolism and Transport, and  Diseases and Treatments

 

Kristen and Robin

 

 

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What is cholesterol?

 

Cholesterol is a soft, waxy substance found among the lipids (fats) in the bloodstream and in all your body's cells. It's an important part of a healthy body because it's used to form plasma membranes, it is the structural basis of steroid hormones and vitamin D, and is needed for other body functions.  Of all the cholesterol in the body, only 15% of blood cholesterol comes from food intake while the remaining 85% is made by the liver. 

 

Cholesterol and other fats can't dissolve in the blood. They have to be transported to and from the cells by special carriers called lipoproteins. There are several kinds, but the ones to focus on are low-density lipoprotein (LDL) and high-density lipoprotein (HDL).

 

 

Low Density Lipoprotein 

LDL, generally considered "bad cholesterol," is a protein in the blood that helps to circulate cholesterol to and from the different cells of the body.  Too much LDL becomes dangerous to one's health because increased numbers of LDL can build up in the arteries of the heart and brain, causing the formation of a hard plaque in the blood vessels that can partially or completely block blood flow: a condition known as artherosclerosis.  Therefore, higher than normal levels of LDL increase the risk of heart attack and stroke because the chances are greater that an artery that nourishes the heart or the brain is impacted.  Anything above 100 mg/DL of LDL cholesterol is considered high and creates an increased risk of heart of heart disease. 

How to Lower Cholesterol

 

Eat a Heart Healthy Diet

  • Food products from animals contain cholesterol — including meats, poultry, shellfish, eggs, butter, cheese and whole or 2 percent milk. And any type of food can also contain saturated fats and trans fats, which cause your body to make more cholesterol.
  • The American Heart Association recommends that you keep your intake of total fat to between 25 percent and 35 percent, your saturated fat consumption to less than 7 percent and your intake of trans fat to less than 1 percent of your total daily calories
  • At the same time, limit your intake of cholesterol from food to less than 300 mg per day. People with high LDL (bad) blood cholesterol levels or who are taking cholesterol medication should consume less than 200 mg of cholesterol per day
  • Eat at least 25 to 30 grams of dietary fiber each day — preferably from whole grains, fruits, vegetables and legumes
  • But a heart-healthy diet isn't just about what you shouldn't eat. It also means eating a diet rich in vegetables and fruits, with whole grains, high-fiber foods, lean meats and poultry, fish at least twice a week, and fat-free or 1 percent fat dairy products. Also, the diet should be low in saturated fat, trans fat and cholesterol

 

 

Drug Therapy

  • Although often a more extreme measure to lower LDL cholesterol, many doctors will subscribe medication for patients whose cholesterol levels will not decrease enough even after lifestyle changes such as diet and exercise
  • Statins (also known as HMG CoA reductase inhibitors)

    This class of drugs works in the liver to prevent the formation of cholesterol. Statins are most effective at lowering the LDL (bad) cholesterol, but also have modest effects on lowering triglycerides (blood fats) and raising HDL (good) cholesterol

    • Atorvastatin (Lipitor®)
    • Rosuvastatin Calcium (Crestor®)
  • Selective cholesterol absorption inhibitors

    This relatively new class of cholesterol-lowering medications works by preventing the absorption of cholesterol from the intestine. Selective cholesterol absorption inhibitors are most effective at lowering the LDL (bad) cholesterol, but may also have modest effects on lowering triglycerides (blood fats) and raising HDL (good) cholesterol.

    • ezetimibe (Zetia®)
  • Resins (also known as bile acid sequestrant or bile acid-binding drugs)

    This class of LDL-lowering drugs works in the intestines by promoting increased disposal of cholesterol.

    • Colestipol (Colestid®) 

 

Lifestyle Changes

  • Often recommended before taking more drastic measures such as drug therapy in order to lower blood cholesterol levels
  • Eating a healthier diet rich in protein and fiber and poor in fats (especially trans fat) is usually the easiest way
  • Exercise and living a more active lifestyle is often recommended
    • regular physical activity affects blood cholesterol level by increasing the level of HDL (good) cholesterol.
    • A higher HDL level is linked with a lower risk of heart disease.
    • Physical activity can also help control other risk factors for heart disease: weight, diabetes and high blood pressure.
    • Aerobic exercise (exercise that uses oxygen to provide energy to large muscles) raises your heart and breathing rates, which help your heart to work more efficiently at rest as well as during physical activity.
    • Vigorous, regular physical activity such as brisk walking, jogging and swimming also condition your lungs

 

 

What is Metabolism?

 

 Metabolism is a broad term defining the series of chemical reactions that occur in the body and are vital in maintaining life.  Each reaction is controlled by a specific protein that is linked to a specific body function.  Metabolism involves two processes: the building up of body tissues and energy (anabolism) and the breaking down of body tissues and energy stores to generate more fuel (catabolism).

 

Catabolism

  Catabolism (destructive metabolism) is the series of metabolic pathways that breaks down large molecules (mostly carbohydrates and fats) into smaller molecules in order to release energy.  The energy released by catabolism is then used in anabolism.  Catabolic reactions can be broken down into three phases:

 1) large organic molecules, like proteins, polysaccharides, or lipids, are digested into their smaller components outside the cell 

 2) these smaller molecules are taken up by the cells and converted into even smaller molecules, usually acetyl coenzyme A (CoA), which releases some energy

 3) the acetyl group on CoA is oxidized to water and carbon dioxide in the citric acid cyle and electron transport chain, relaeasing the rest of the energy that is stored

 

Anabolism 

 Anabolism (constructive metabolism) uses energy to support the growth of new cells, the maintenance of body tissues, and the storage for energy for use in the future.  In this process, small molecules are changed into larger molecules, such as carbohydrates, proteins, and fats.  Anabolic reactions can be broken down into three phases as well:

 1) production of precursors, such as amino acids, soprenoids, nucleotides, and monosaccharides 

 2) these precursors are changed into their active forms using ATPs 

 3) these active precursors are assembled into more complex molecules 

 

Though these two processes are used in all metabolic processes, the body has different methods to break down different substances.  Below will be described the processes by which the body breaks down carbohydrates, fats, and proteins.

 

Carbohydrate Metabolism

Carbohydrates are the preferred fuel for cellular energy.  Glucose is the breakdown product of carbohydrate digestion and the major fuel used for the creation of ATP.  In order to create this ATP, glucose is broken down piece by piece, releasing chemical energy as each bond is broken.  To complete this breakdown and to harvest the energy available in carbohydrates three metabolic pathways are used: glycolysis, the Krebs Cycle, and the Electron Transport Chain.

 

  "Carbohydrate metabolism begins with glycolysis, which releases energy from glucose or glycogen to form two molecules of pyruvate, which enter the Krebs cycle (or citric acid cycle), an oxygen-requiring process, through which they are completely oxidized. Before the Krebs cycle can begin, pyruvate loses a carbon dioxide group to form acetyl coenzyme A (acetyl-CoA). This reaction is irreversible and has important metabolic consequences. The conversion of pyruvate to acetyl-CoA requires the B vitamins.

 

 The hydrogen in carbohydrate is carried to the electron transport chain, where the energy is conserved in ATP molecules. Metabolism of one molecule of glucose yields thirty-one molecules of ATP. The energy released from ATP through hydrolysis (a chemical reaction with water) can then be used for biological work." 

 

Patel, Gita. "Metabolism." Nutrition and Wellbeing A-Z. 04/13/2009. http://www.faqs.org/nutrition/Met-Obe/Metabolism.html.

 

 

Protein Metabolism

Proteins make up the majority of all cellular structures within the body.  When ingested, proteins are broken down into amino acids which are then taken up by the liver.  The excess amino acids that are not used by the liver then begin to circulate to the body cells where they are used to build proteins.  In order to use these amino acids, the cells must actively transport these amino acids through their membrane and at times will even transport amino acids that they are not currently in need of so they can store them for future use.  This seemingly unnecessary intake of amino acids is a preventative major warranted by the fact that in order for protein synthesis to occur, every amino acid must be present; therefore, cells store these amino acids to guarantee that they will be available in the future. Only if there is an excess of proteins in the body or a deficiency of carbohydrates and fats will the body use amino acids to produce ATP as is explained in the excerpt below:

"If amino acids are in excess of the body's biological requirements, they are metabolized to glycogen or fat and subsequently used for energy metabolism. If amino acids are to be used for energy their carbon skeletons are converted to acetyl CoA, which enters the Krebs cycle for oxidation, producing ATP. The final products of protein catabolism include carbon dioxide, water, ATP, urea, and ammonia."

Patel, Gita. "Metabolism." Nutrition and Wellbeing A-Z. 04/13/2009. <http://www.faqs.org/nutrition/Met-Obe/Metabolism.html>.

 

 

 

Fat Metabolism

The Liver deals with most of the fat metabolism by processing some fats to produce ATP or using some fats to synthesize lipoproteins, thromboplastin, and cholesterol.  Whatever fat is not metabolized by the liver is then released into the blood stream in the form of small break down fat deposits for the use of the body cells in building their membranes or creating steroids.  Another use of this fat is to harvest the large amounts of ATP that is available in stored fats.  This amount equates to the catabolism of 1 g of fat yielding twice as much ATP as 1 g of protein or carbohydrate.  In order to harvest the stored energy in fat, the following metabolic pathways are used: lipolysis, betaoxidation, ketosis, and lipogenesis.

 

"Lipolysis (fat breakdown) and beta-oxidation occurs in the mitochondria. It is a cyclical process in which two carbons are removed from the fatty acid per cycle in the form of acetyl CoA, which proceeds through the Krebs cycle to produce ATP, CO2, and water.

Ketosis occurs when the rate of formation of ketones by the liver is greater than the ability of tissues to oxidize them. It occurs during prolonged starvation and when large amounts of fat are eaten in the absence of carbohydrate."

Patel, Gita. "Metabolism." Nutrition and Wellbeing A-Z. 04/13/2009. <http://www.faqs.org/nutrition/Met-Obe/Metabolism.html>. 

 

 

Metabolism

 

*if you are having trouble reading this diagram, go to this site http://www.faqs.org/nutrition/Met-Obe/Metabolism.html for the original version

 

 The Liver in Metabolism

The liver functions as the body's main metabolic organ, processing all nutrients that enter the body to remove substances such as amino acids, fatty acids, and glucose from the body and to detoxify and remove bacteria from harmful substances in the blood stream.  Three metabolic processes performed by the liver are: glycogenesis, glycogenolysis, and gluconeogenesis.

 

 

Glycogenesis

Glycogenesis is the process by which the glucose molecules in the blood combine to form large polysaccharide molecules called glycogen.

 

Glycogenolysis

Later on, after the body cells have removed sufficient glucose to support their needs and blood glucose levels have begun to drop, the process of glycogenolysis occurs.  In glycogenolysis, the liver cells break down the stored glycogen and release glucose into the blood stream to combat the dropping blood glucose levels.

 

Gluconeogenesis

The liver also has the ability to create glucose from substances such as fats and proteins in a process called gluconeogenesis.

 

Visit http://www.elmhurst.edu/~chm/vchembook/604glycogenesis.html for a good explanation of the different steps and conversions involved in these three processes and some diagrams of how these processes work. 

 

 

 Metabolism Problems

 

In a broad sense, a metabolic disorder is any disease that is caused by an abnormal chemical reaction in the body's cells. Most disorders of metabolism involve either abnormal levels of enzymes or hormones or problems with the functioning of those enzymes or hormones. When the metabolism of body chemicals is blocked or defective, it can cause a buildup of toxic substances in the body or a deficiency of substances needed for normal body function, either of which can lead to serious symptoms.

Some metabolic diseases are inherited. These conditions are called inborn errors of metabolism. When babies are born, they're tested for many of these metabolic diseases in a newborn screening test. Many of these inborn errors of metabolism can lead to serious complications or even death if they're not controlled with diet or medication from an early age. 

 

 Examples of metabolic disorders and conditions include:

 

 

G6PD deficiency. Glucose-6-phosphate dehydrogenase, or G6PD, is just one of the many enzymes that play a role in cell metabolism. G6PD is produced by red blood cells and helps the body metabolize carbohydrates. Without enough normal G6PD to help red blood cells handle certain harmful substances, red blood cells can be damaged or destroyed, leading to a condition known as hemolytic anemia. In a process called hemolysis, red blood cells are destroyed prematurely, and the bone marrow (the soft, spongy part of the bone that produces new blood cells) may not be able to keep up with the body's need to produce more new red blood cells. Kids with G6PD deficiency may be pale and tired and have a rapid heartbdeficiency.

 Treatment: G6PD deficiency is usually treated by discontinuing any drugs or medications that may have caused the deficiency. The hemolytic anemia must be treated as well; therefore, blood transfusions may be necessary in very sever cases.

 Galactosemia. Babies born with this inborn error of metabolism do not have enough of the enzyme that breaks down the sugar in milk called galactose. This enzyme is produced in the liver. If the liver doesn't produce enough of this enzyme, galactose builds up in the blood and can cause serious health problems. Symptoms usually occur within the first days of life and include vomiting, swollen liver, and jaundice. If galactosemia is not diagnosed and treated quickly, it can cause liver, eye, kidney, and brain damage.

 

 Treatment: Treatment for galactosemia is the elimination of galactose and lactose from the diet throughout life.  A person with galactosemia will never be able to properly digest foods containing galactose.  There is no chemical or drug substitute for the missing enzyme at this time.  An infant diagnosed with galactosemia will simply be changed to a soy-based formula that does not contain galactose.  Galactosemia is often confused with lactose intolerance, but please keep in mind that galactosemia is a disease.  A person with galactosemia will not "grow out of" it.

 

Hyperthyroidism. Hyperthyroidism is caused by an overactive thyroid gland. The thyroid releases too much of the hormone thyroxine, which increases the person's basal metabolic rate (BMR). It causes symptoms such as weight loss, increased heart rate and blood pressure, protruding eyes, and a swelling in the neck from an enlarged thyroid (goiter).

 

 Treatment: There are three ways in which hyperthyroidism can be treated.  The most common methods of treatment are antithyroid medications and radioactive iodine, though in some severe cases surgery may be required as the third treatment.  In many cases, antithyroid medication is used as initial treatment to make a patient feel better and then further action can be decided on from there based on the severity of the symptoms.

 

 

Hypothyroidism. Hypothyroidism is caused by an absent or underactive thyroid gland and it results from a developmental problem or a destructive disease of the thyroid. The thyroid releases too little of the hormone thyroxine, so a person's basal metabolic rate (BMR) is low. In infants and young children who don't get treatment, this condition can result in stunted growth and mental retardation. Hypothyroidism slows body processes and causes fatigue, slow heart rate, excessive weight gain, and constipation.

 

 Treatment: Hypothyroidism can be easily treated using thyroid hormone medicine.  Generally, symptoms will begin to improve within the first week and will dissappear completely within a few months.

 

 

Phenylketonuria. Also known as PKU, this condition occurs in infants due to a defect in the enzyme that breaks down the amino acid phenylalanine. This amino acid is necessary for normal growth in infants and children and for normal protein production. However, if too much of it builds up in the body, brain tissue is affected and mental retardation occurs. Early diagnosis and dietary restriction of the amino acid can prevent or lessen the severity of these complications. 

 

Treatment: Phenylketonuria is treated by using diet therapy to help prevent retardation.  Generally, people who suffer from PKU must follow a strict phenylalanine-low diet. Since phenylalanine occurs in almost all natural proteins, maintaining proper nutrition is difficult on a phenylalanine-low diet. Dietary use of special phenylalanine-free preparations is therefore essential. These include Lofenalac (for a low phenylalanine diet) and Phenyl-Free, both from Mead Johnson. Low protein foods such as fruits, vegetables, and some cereals are also allowed.

 

 

Type 1 diabetes mellitus. Type 1 diabetes, once known as juvenile diabetes or insulin-dependent diabetes, is a chronic condition in which the pancreas produces little or no insulin, a hormone needed to convert sugar (glucose) into energy. Although type 1 diabetes can develop at any age, it typically appears during childhood or adolescence.

Treatment: Type 1 diabetes is treated through a combination of taking and monitoring insulin as well as lifestyle changes that include monitoring weight, eating a healthy diet, and minimzing alcohol intake. It is very important to understand how foods and beverages intaken into the body can affect the blood sugar level.  Treatment of diabetes almost always involves the daily injection of insulin, usually a combination of short-acting insulin [for example, lispro (Humalog) or aspart (NovoLog)] and a longer acting insulin [for example,  NPH, Lente, glargine (Lantus), detemir, or ultralente]

 Type 2 diabetes. Type 2 diabetes happens when the body can't respond normally to insulin. The symptoms of this disorder are similar to those of type 1 diabetes. Many kids who develop type 2 diabetes are overweight, and this is thought to play a role in their decreased responsiveness to insulin. Some can be treated successfully with dietary changes, exercise, and oral medication, but insulin injections are necessary in other cases. Controlling blood sugar levels reduces the risk of developing the same kinds of long-term health problems that occur with type 1 diabetes.

 

Treatment: Treatment for type 2 diabetes is a lifelong commitment of blood sugar monitoring, healthy eating, regular exercise and, sometimes, diabetes medications or insulin therapy. The goal is to keep blood sugar levels as close to normal as possible to delay or prevent complications. In fact, tight control of blood sugar levels can reduce the risk of diabetes-related heart attacks and strokes by more than 50 percent

 

 

 High Cholesterol: Diseases Linked to High Cholesterol

High cholesterol increases the risk of other conditions, depending on which blood vessels are narrowed or blocked. These diseases include: coronary heart disease, stroke and peripheral vascular disease. High cholesterol has also been linked to diabetes and high blood pressure. To prevent or manage these conditions, take steps to lower your cholesterol if it is elevated.

 

 

 

 

Coronary Heart Disease

 

The main risk associated with high cholesterol is coronary heart disease (CHD). Your blood cholesterol level has a lot to do with your chances of getting heart disease. If cholesterol is too high, it builds up in the walls of your arteries. Over time, this buildup (called plaque) causes hardening of the arteries (atherosclerosis). Atherosclerosis causes arteries to become narrowed, slowing blood flow to the heart. Reduced blood flow to the heart can result in angina (chest pain) or in a heart attack in cases when a blood vessel is blocked completely.

Treatment: The most effective way to prevent coronary heart disease is through lifestyle changes that help to lower cholesterol and prevent plaque build up in the arteries that could lead to heart attack.  Eating a low fat, heart healthy diet, exercising regularly, lowering cholesterol, and quitting smoking, and taking low dose aspirin are effective ways to prevent and lower the risk of coronary heart disease.  In more severe cases, treatment may be recommended in the form of aspirin, which lowers bloods tendency to clot, beta blockers, which decrease heart rate and blood pressure, calcium channel blockers, which dilate the coronary arteries, statins, which reduce the amount of lipids in the blood, or in cases where medication is not effective enough, invasive surgeries, such as angioplasties or stents, may be used to clear the blocked arteries.

 

 

 

 

Stroke

 

Stroke can result if the blood supply to part of the brain is reduced. A stroke occurs when a blood vessel that carries oxygen and nutrients to the brain becomes blocked or bursts. Blood vessels may become blocked as a result of plaque build up from too much cholesterol. When stroke occurs, part of the brain cannot get the blood and oxygen it needs, so it starts to die.

Treatment: Initial treatment for a stroke varies depending on whether it's caused by a blood clot (ischemic) or bleeding in the brain (hemorrhagic).  If a stroke is ischemic, initial treatment focuses on restoring blood flow to the brain by using clot dissolving medications or aspiring to help the blood flow more easily.  In contrast, if a stroke is hemorrhagic, initial treatment usually consists of controlling bleeding, reducing pressure in the brain, and stabilizing vital signs.  If the stroke is due to an aneurysm, surgery will be done to stop bleeding from the blood vessel.  After emergency treatment has been completed and the patient is stable, daily measures will be taken to reduce the risk of another stroke by reducing risk factors such as high blood pressure, atrial fibrillation, high cholesterol, and diabetes.  Doctors will commonly recommend taking aspirin on a daily basis and sometimes recommend other medications such as anticoagulants or blood pressure medicines, such as beta blockers and calcium channel blockers.

 

 High Blood Pressure

High blood pressure (also called hypertension) and high cholesterol also are linked. When the arteries become hardened and narrowed with cholesterol plaque and calcium (atherosclerosis), the heart has to strain much harder to pump blood through them. As a result, blood pressure becomes abnormally high. High blood pressure is also linked to heart disease.

 

Treatment: If blood pressure exceeds 140/90 mm Hg, it is usually treated through lifestyle changes and medication.  Lifestyle changes include maintaining a healthy weight, eating a low fat, heart healthy diet, limiting alcohol intake, quitting smoking, and exercising regularly. If these lifestyle changes are not sufficient in lowering blood pressure, doctors will perscribe medications such as diuretics, which help to flush out extra water and sodium from the body;beta blockers, which causing the heart to beat more slowly and with less force;angiotensin converting enzyme inhibitors, which prevents the porduction of angiotensin II hormon that causes blood vessels to narrow;angiotensin antagonists, which shield blood vessels from angiotensin II;calcium channel blockers, which keeps calcium from entering the blood vessels near the heart; alpha blockers, which reduce nerve impulses and allow blood to flow more freely; nervous system inhibitors, which relax blood vessels by controlling nerve impulses; and vasodilators, which directly open blood vessels by relaxing the blood vessel walls.

 

  

Comments (1)

csnanatomy said

at 2:49 pm on Apr 2, 2009

It is now recommended that LDL cholesterol be less than 100. Is diet effective for many people for lowering LDL cholesterol?

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