1. Cholesterol and C.V.D.

2. Learning outcome Most cholesterol is synthesised by the liver from saturated fats in the diet. Cholesterol is a component of cell membranes and a precursor for steroid synthesis. High-density lipoprotein (HDL) transports excess cholesterol from the body cells to the liver for elimination. This prevents accumulation of cholesterol in the blood. Low-density lipoprotein (LDL) transports cholesterol to body cells. Most cells have LDL receptors that take LDL into the cell where it releases cholesterol. Once a cell has sufficient cholesterol a negative feedback system inhibits the synthesis of new LDL receptors and LDL circulates in the blood where it may deposit cholesterol in the arteries forming atheromas. A higher ratio of HDL to LDL will result in lower blood cholesterol and a reduced chance of atherosclerosis.

3. Regular physical activity tends to raise HDL levels, dietary changes aim to reduce the levels of total fat in the diet and to replace saturated with unsaturated fats. Drugs such as statins reduce blood cholesterol by inhibiting the synthesis of cholesterol by liver cells. Familial hypercholesterolaemia (FH) due to an autosomal dominant gene predisposes individuals to developing high levels of cholesterol. FH genes cause a reduction in the number of LDL receptors or an altered receptor structure. Genetic testing can determine if the FH gene has been inherited and it can be treated with lifestyle modification and drugs.

4. Cholesterol is an important substance – It is a precursor for the synthesis of steroids such as sex hormones It is a basic component of cell membranes Lipoproteins are present in the plasma and transport lipids around the body Low-density lipoproteins These are produced by the liver and they transport cholesterol to body cells

5. Most cells make LDL receptors which become inserted in the cell membrane LDL carrying cholesterol (LDL-cholesterol) becomes attached to a receptor The cell then engulfs the LDL-cholesterol The cholesterol is released for use by the cell When the cell has enough cholesterol for its needs, the synthesis of new LDL receptors is inhbited

6. People who eat a diet rich in saturated fat, and People with an inherited condition called Familial Hypercholesterolaemia have LDL-cholesterol circulating in their bloodstream Cholesterol can become deposited in an atheroma in an artery wall LDL – cholesterol molecules are sometimes called ‘bad cholesterol’ (Another molecule, High-density lipoprotein- cholesterol is sometimes called ‘good cholesterol’)

7. High-density lipoprotein Some excess cholesterol is taken from body cells to the liver by high-density lipoproteins This usually prevents a high level of cholesterol accumulating in the bloodstream HDL-cholesterol is not taken into artery walls, therefore does not contribute to atherosclerosis These benefits depend on a ‘Healthy Balance’ between the LDL-cholesterol molecules and the HDL- cholesterol molecules

8. A high ratio of HDL to LDL results in a decrease in blood cholesterol and a reduced chance of atherosclerosis and cardiovascular disease A lower ratio of HDL to LDL results in an increase in blood cholesterol and an increased chance of atherosclerosis and cardiovascular disease HDL levels may be raised by eating less fat Statins – Drugs such as statins reduce cholesterol levels in the blood They inhibit an enzyme essential for the synthesis of cholesterol by liver cells

9. Familial Hypercholesterolaemia Molecules of LDL-cholesterol bind to LDL receptors on cell membranes Sufferers of FH have a mutated gene that causes a decrease in the number of LDL receptors in the cell membrane Molecules of LDL-cholesterol are unable to unload the cholesterol in cells Sufferers have very high LDL-cholesterol in their bloodstream If left untreated, large quantities of cholesterol are deposited in the walls of arteries Statins work by inhibiting the enzyme needed for the synthesis of cholesterol by liver cells

10. Now try these questions.... 1. Why is cholesterol an important substance? 2. What are low density lipoproteins? 3. Why is LDL- cholesterol called ‘bad cholesterol’? 4. What is the function of high density lipoproteins? 5. What is the function of drugs such as ‘Statins’?

11. 1. Why is cholesterol an important substance? It is a precursor for the synthesis of steroids such as sex hormones It is a basic component of cell membranes Lipoproteins are present in the plasma and transport lipids around the body 2. What are low density lipoproteins? These are produced by the liver and they transport cholesterol to body cells 3. Why is LDL- cholesterol called ‘bad cholesterol’? This type can become deposited in an atheroma in an artery wall

12. 4. What is the function of high density lipoproteins? Some excess cholesterol is taken from body cells to the liver by high-density lipoproteins This usually prevents a high level of cholesterol accumulating in the bloodstream HDL-cholesterol is not taken into artery walls, therefore does not contribute to atherosclerosis 5. What is the function of drugs such as ‘Statins’? Drugs such as statins reduce cholesterol levels in the blood They inhibit an enzyme essential for the synthesis of cholesterol by liver cells, Statins work by inhibiting the enzyme needed for the synthesis of cholesterol by liver cells