Wilu's paper: chapter 2, cholesterol

CHAPTER 2 CHOLESTEROL 2.1 Definition Cholesterol is a sterol (a combination steroid and steroid), a lipid found in the cell membranes of all body tissues, and is transported in the blood plasma of all animals. Trace amounts of cholesterol are also found in plant membranes.The name originates from the Greek chole- (bile) and stereos (solid), and the chemical suffix -ol for an alcohol, as researchers first identified cholesterol in solid form in gallstones in 1784. Cholesterol is a soft, fat-like, waxy substance found in the bloodstream and in all your body's cells. It's normal to have cholesterol. Cholesterol is an important part of a healthy body because it's used for producing cell membranes and some hormones, and serves other needed bodily functions. But too much cholesterol in the blood is a major risk for coronary heart disease (which leads to heart attack) and for stroke. Cholesterol also aids in the manufacture of bile (which is stored in the gallbladder and helps digest fats), and is also important for the metabolism of fat soluble vitamins, including vitamins A,D,E and K. It is the major precursor for the synthesis of vitamin D and of the various steroid hormones (which include cortisol and aldosterone in the adrenal glands, and the sex hormones progesterone, the various estrogens, testosterones, and derivates). There are different kinds of cholesterol. The liver converts unburned food metabolites into very low density lipoproteins (VLDL) and secretes them into plasma where they are converted to low-density lipoprotein (LDL) particles and non-esterified fatty acids, which can affect other body cells. In healthy individuals, the relatively few LDL particles are large. In contrast, large numbers of small dense LDL (sdLDL) particles are strongly associated with the presence of atheromatous disease within the arteries. For this reason, LDL is referred to as "bad cholesterol". High-density lipoprotein (HDL) particles transport cholesterol back to the liver for excretion, but vary considerably in their effectiveness for doing this. Having large numbers of large HDL particles correlates with better health outcomes, and hence it is commonly called "good cholesterol". In contrast, having small amounts of large HDL particles is independently associated with atheromatous disease progression within the arteries. 2.2 Synthesize of cholesterol Most of the cholesterol is synthesized by the body and some has dietary origin. Although formerly believed, the cholesterol level in blood is not raised by increasing the amount of cholesterol in the diet. Cholesterol is more abundant in tissues which either synthesize more or have more abundant densely-packed membranes, for example, the liver, spinal cord, brain, and atheromata (arterial plaques). Cholesterol plays a central role in many biochemical processes, but is best known for the association of cardiovascular disease with various lipoprotein cholesterol transport patterns and high levels of cholesterol in the blood. Cholesterol is insoluble in blood, but is transported in the circulatory system bound to one of the varieties of lipoprotein, spherical particles which have an exterior composed mainly of water-soluble proteins. Cholesterol is required in the membrane of mammalian cells for normal cellular function, and is either synthesized in the endoplasmic reticulum, or derived from the diet, in which case it is delivered by the bloodstream in low-density lipoproteins. These are taken into the cell by receptor-mediated endocytosis in clathrin-coated pits, and then hydrolysed in lysosomes. Cholesterol is primarily synthesized from acetyl coA through the HMG-CoA reductase pathway in many cells and tissues. About 20-25% of total daily production (~1 g/day) occurs in the liver; other sites of higher synthesis rates include the intestines, adrenal glands and reproductive organs. For a person fo about 150 pounds (68kg), typical daily dietary intake is 200 to 300 mg. Of the cholesterol input to the intestines via bile production, 92-97% is reabsorbed in the intestines and recycled via enterohepatic circulation. Biosynthesis of cholesterol is directly regulated by the cholesterol levels present, though the homeostatic mechanisms involved are only partly understood. A higher intake from food leads to a net decrease in endogenous production, while lower intake from food has the opposite effect. The main regulatory mechanism is the sensing of intracellular cholesterol in the endoplasmic reticulum by the protein SREBP (Sterol Regulatory Element Binding Protein 1 and 2). In the presence of cholesterol, SREBP is bound to two other proteins: SCAP (SREBP-cleavage activating protein) and Insig1. When cholesterol levels fall, Insig-1 dissociates from the SREBP-SCAP complex, allowing the complex to migrate to the Golgi apparatus, where SREBP is cleaved by S1P and S2P (site 1/2 protease), two enzymes that are activated by SCAP when cholesterol levels are low. The cleaved SREBP then migrates to the nucleus and acts as a transcription factor to bind to the SRE (sterol regulatory element) of a number of genes to stimulate their transcription. Among the genes transcribed are the LDL receptor and HMG-CoA reductase. The former scavenges circulating LDL from the bloodstream, whereas HMG-CoA reductase leads to an increase of endogenous production of cholesterol. 2.3 The Risk Factors You're more likely to have high cholesterol if you're inactive, obese or eat unhealthy foods. Although high cholesterol can lead to heart disease on its own, other factors compound the risk: · Smoking. Cigarette smoking damages the walls of your blood vessels, making them likely to accumulate fatty deposits. Smoking may also lower your level of HDL cholesterol. · High blood pressure. Increased pressure on your artery walls damages your arteries, which can speed the accumulation of fatty deposits. · Diabetes. High blood sugar contributes to high LDL cholesterol and low HDL cholesterol. High blood sugar also damages the lining of your arteries. · Family history of heart disease. If a parent or sibling developed heart disease before age 55, high cholesterol levels place you at a greater than average risk of developing heart disease. 2.4 Screening and Diagnosis Cholesterol screening and diagnosis maybe done either by testing the entire adult population or by making use of routine contacts in primary health care (opportunistic screening). The main screening test for blood cholesterol is the measurement of total blood cholesterol in blood samples obtained by either venepuncture or finger prick. Measurements in cholesterol screening may not accurately reflect the true cholesterol level due to measurement error (bias and imprecision) and natural biological variation in cholesterol levels within an individual. These sources of error can result in misclassification and lead to incorrect diagnosis and the possibility of unnecessary treatment. However, bias can be reduced in laboratory equipment by regular calibration againts a standard, and precision increased by using good equipment and repeat analyses. 2.5 Preventions To keep our cholesterol under control, we must do the following : - Schedule a screening - Eat foods low in cholesterol and saturated fat - Maintain a healthy weight - Exercise regularly - Follow the healthcare professional's advice

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