CHOLESTEROL

Introduction: Cholesterol is the principal animal sterol and as it is a constituent of cell membrane, it has been found in all animal tissues. In simple terms we can call Cholesterol is a kind of fat molecule or Lipid. Fats consumed by human being from animal sources come in a form of triglycerides called saturated fats. Getting too much of this sort of fat into our systems creates cholesterol deposits. The synthesizing organs in human for Cholesterol are Liver & Intestine. Cholesterol is the precursor of five major classes of steroid hormones i.e. Progesterone, Testosterone, Oestrone, Cortisol & Aldosterone and Bile salts; hence it's very much crucial for normal body functioning. Physically it is described as a kind of waxy fat material. But, apart from the useful amount of Cholesterol, both the low level and high level are associated with greater risks to metabolic disorders and may lead to certain chronic disorders also. The way down to end of this article we'll get a better idea about the structure, function and diseases associated to Cholesterol. Structure: Cholesterol is a 27-C molecule having the chemical formula of C27H45OH and the IUPAC name is (3 )-cholest-5-en-3-ol . As the structural figure describes it's composed of 3 regions; A hydroxyl group (Red box), 4-hydrocarbon rings (Green Box) and a hydrocarbon tail (Blue box).

The Hydroxyl group is polar, which makes this molecule soluble in water and this OH is responsible for making Cholesterol into alcohol group. The 4-hydrocarbon rings are responsible for the synthesis of steroid hormones. The last region of hydrocarbon tail is also composed of C & H. Both the hydrocarbon regions simultaneously are non polar, means are soluble in fatty and oil substances but insoluble in water. As Cholesterol contains both a water soluble & fat soluble region it's called amphipathic. The fused ring system of cholesterol makes it more rigid than other membrane lipids. The combination of hydroxyl group and steroid rings classifies Cholesterol as Sterol. However it is not enough soluble to water to dissolve in Blood, hence it travels in blood along with fat & fat soluble nutrients. When formed, these cholesterols attach themselves to two types of carrier proteins called HDL (High Density Lipoprotein) and LDL (Low Density Lipoprotein). In addition to the synthesis of Cholesterol, it can be derived from the diet or can be synthesized in Liver. Animals can synthesize cholesterol in a series of elegant reactions where all the 27 C atoms are derived from Acetyl CoA. The acetate units are first converted into C5 isoprene units which are condensed to form a linear precursor to the cyclic cholesterol called the C30 compound Squalene. Squalene is then converted into Squalene epoxide which cyclizes to form Ianosterol and finally cholesterol is formed from Ianosterol after removal of three methyl groups, reduction of one double bond by NADPH and migration of the remaining double bond. The rate of synthesis of Cholesterol is dependent on the cellular level of cholesterol. Function: Earlier we have discussed cholesterol as a Lipid molecule, hence the main function of cholesterol is building and maintaining of cell membrane. It serves as a kind of building block for body tissues without its support, mammalian life would not be possible. It is essential for the determination of molecules for cell membrane permeability. It also prevents crystallization of hydrocarbons in the membrane. Over a range of physiological

temperature, it modulates the membrane fluidity of cell membranes. The steroid rings and hydrocarbon chain interact with the nonpolar fatty acid chain of other lipids and are embedded in the membrane while the hydroxyl group interact to the polar heads of the membrane lipids. This specific interaction leads to close membrane packing in a result it reduces membrane fluidity. Cholesterol is absent in prokaryotes but is found almost in all animal membranes. Almost 25% of the membrane lipids in certain nerve cells are cholesterol but it's essentially absent from some intracellular membranes. Within cells it acts as the precursor molecule in several biochemical pathways including in the liver, the manufacture of steroids or cortisone like hormones, vitamin D and several sex hormones and assists the liver in the manufacture of bile acids, which is essential for digestion and absorption of fat-soluble vitamins. Cholesterol helps in formation of myelin sheath. It's a neuron consisting of fat-containing cells which works as insulator for the axon during electrical activity. By aiding route to electrical impulses it ensures proper functioning of our brain. Absence of cholesterol may lead to loss of memory or improper functioning. In concern to the movement of cholesterol in blood stream, as we discussed earlier it moves along with HDL and LDL. Cholesterol attached to LDL proteins (Cholesterol-LDL complex) has a negative function within the body. These cholesterol molecules attach themselves to the walls of the blood vessels and arteries, resulting narrowness inside the vessels and arteries. This narrowing of the arterial pathways can cause a heart attack. Cholesterol attached to HDL (Cholesterol-HDL complex) has a beneficial function within the body. HDL cholesterol molecules are able to attach themselves to harmful LDL molecules and carry them off to the liver where they are broken down and excreted from the body. Bile salts are the major excretory form of cholesterol. These compounds (Bile) are formed in the

liver by converting cholesterol into activated intermediate cholyl CoA and then combining this compound with either glycine, to form glycocholate, or taurine, to form taurocholate. The detergent like bile salts are secreted into the intestine where they help in digestion and uptake of dietary lipids. Another function of cholesterol is the synthesis of Vitamin D. Vitamin D is synthesized via cholesterol in a series of reactions, one of which requires the action of Sun light to break the bond between two carbon atoms. Deficiency of vitamin D causes rickets in children and osteomalacia in adults. Few more functions of cholesterol we can highlight here not going to details: It helps in building strong bones and strengthens muscles resulting in healthy life. Cholesterol is said to form a protective coating to the body and arteries so that we remain away from infectious diseases. y Researchers believe that cholesterol is the best solution that regulates body sugar along with repairing damaged tissues as it has a crucial role in the formation of insulin. y Cholesterol facilitates production of hormones which assist with healing your body from injuries or infections. y A finding published in the American Journal of Medicine over twenty years ago showed that too low cholesterol levels increase the risks for an early death. y y Cholesterol is considered as a source of energy. Maintenance of our body temperature is also facilitated by cholesterol.

y y

Diseases associated with Cholesterol: When the term Cholesterol comes to our mind another thing comes along with it; Heart diseases, as this disorder is directly associated with high cholesterol level. Nevertheless both the high and low level of cholesterol apart from the normal level are linked to some typical disorders. In this section we'll discuss a few.

Starting the discussion with high cholesterol level in body which is referred to High LDL cholesterol level is directly associated with Heart disorders. The higher the level of LDL cholesterol in our blood, the GREATER our chance is of getting heart disease. The major disorder of heart is the Coronary Heart Disease or Coronary Artery Disease. CHD is a condition in which plaque builds up inside the coronary arteries. Plaque is made up of cholesterol, fat, calcium, and other substances found in the blood. When plaque builds up in the arteries, the condition is called atherosclerosis. In later stages these plaque become harder and the narrowing of arteries start resulting in limiting the flow of Oxygen rich blood to heart muscles. Gradually the rupture of plaque causes blood clot which eventually leads to mostly or completely block of blood flow through a coronary artery. This in a very later stage raises the chance of occurrence of angina or heart attack. This typical condition of abnormal high cholesterol-LDL level is called Hypercholesterolemia. Peripheral arterial disease is a chronic condition caused by atherosclerosis that most commonly affects the limbs of the body. For a fact, our body produces enough cholesterol sufficient for our internal needs, the extra cholesterol is the direct result of what we intake in the form of food. High cholesterol also has been linked to peripheral vascular disease, which refers to diseases of blood vessels outside the heart and brain. In this condition, fatty deposits build up along artery walls and affect blood circulation, mainly in arteries leading to the legs and feet. The association of Diabetes and high LDL cholesterol levels lead to heart and artery diseases. Sugar-coated LDL (Glucose attaches to lipoproteins) remains in the bloodstream longer and may lead to the formation of plaque. People with diabetes tend to have low HDL and high LDL levels, both of which boost the risk of heart and artery disease. The link between High Blood Pressure and high LDL level is well known. As a result of the plaque formation the arteries become hardened and narrowed. This insists the heart 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. Stroke causes when 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 as a result of plaque formation. When stroke occurs, part of the brain cannot get the blood and oxygen it needs, so it starts to die. Liver dysfunction is also associated with cholesterol level but in a reverse way. The changes in LDL/HDL level are mainly a result of Liver dysfunction. Hypocholesterolemia is the condition which describes abnormally low levels of cholesterol in the blood. A defect in the body's production of cholesterol can lead to adverse consequences, which are being experimented. A few highlighted disorders are: Low cholesterol level might lead to loss of memory or improper functioning. As we discussed earlier in the function section, how cholesterol has a crucial role in maintaining the nervous system function. So the low level of cholesterol will lead to the damage of axon during electrical activity, which might lead to mental disorder or improper function of brain and nervous system. One of the studies has found; in men, low levels of low density lipoprotein (LDL) cholesterol were associated with an increased risk of depression and in women, low levels of high density lipoprotein (HDL) cholesterol were associated with an increased risk of depression. Cholesterol levels may influence serotonin activity in the brain. Serotonin is the neurotransmitter associated with mood, and low serotonin is associated with depression and violent and anti-social behaviour. Some other disorders like hyperthyroidism, adrenal insufficiency, liver diseases, malabsorption, malnutrition, manganese deficiency, leukaemia etc. are associated with Cholesterol whereas directly or indirectly in accordance to the level.

In the elderly, studies over several decades have pointed to increased risk of death in the population with the lowest cholesterol which is a sign of increasing morbidity. Conclusion: Cholesterol has been portrayed by some as tantamount to a poison. In fact, cholesterol is a versatile compound that is vital (in small amounts) to the functioning of the human body. Only animals produce it; no plant product contains cholesterol unless an animal- based product, such as lard, has been added to it in processing. The problem with cholesterol arises when the body has too much of it, or has deposits of it in the wrong places. Cholesterol metabolism is based on the fact that oil and water dont mix. It's recommended by most of the physicians for regular checkups of cholesterol level and maintaining the usual normal level. Various scoring systems are available to help estimate an individual's overall cholesterol level which are simple to use and can help clinicians make treatment decisions on the basis of the diagnosed cholesterol level avoiding risk.

REFERENCES BOOKS 1. The Role of Cholesterol, Jonathan Isaacsohn. 2. Instant notes of Biochemistry, B.D. Hames & N. M. Hooper 3. Basic concepts in Biochemistry, Hivam F. Gilbert 4. Study Guide Biology by Robert G. Turner. 5. Enger-Ross : Concepts in Biology. 6. Encyclopaedia of Life sciences. y y Cholesterol and Vascular Disease, SH Wild & CD Byrne. Cholesterol-lowering Agents and their Use, Christopher J Packard, Allan Gaw & James Shepherd. 7. Medicinal Natural Products, Paul M. Dewick. 8. Biology: Macmillan Science Library. 9. Biochemistry by Lubert Stryer. WEBSITES 1. www.webmd.com 2. www.cholesterol.about.com 3. www.wikibooks.org 4. www.wikipedia.org 5. www.choleaterol-and-health.com 6. www.ehow.com