Cholesterol

What is cholesterol?

(1) Structure of Cholesterol

Cholesterol has a total of 27 carbon (C) atoms. Cholesterol is a sterol as it has a hydroxyl (-OH) group at carbon #3 (C3) - only this hydroxyl group is hydrophilic in cholesterol. Cholesterol is a stable molecule as it has a rigid hydrophobic steroid nucleus (rings A, B, C and D) which is not easily degraded by human enzymes. It is  has an aliphatic hydrophobic tail with eight carbons (8C). It has a carbon-carbon double bond between carbon #5 and carbon #6 (C5=C6). It has 5 methyl (-CH3) groups at C18, C19, C21, C26 and C27. 

(2) Function of Cholesterol

Cholesterol is produced by the liver and is found in all body tissues. It helps to organize cell membranes and control their permeability, and therefore avoid cancer formation. Cholesterol derivatives in the skin are converted to vitamin D when the skin is exposed to sunlight. Vitamin D₃ mediates intestinal calcium absorption and bone calcium metabolism. Cholesterol is a precursor to many physiologically important steroids, such as bile acids & salts and steroid hormones. Examples of steroid hormones are testosterone, progesterone, and cortisol.

(3) Cholesterol Synthesis

Cholesterol synthesis occurs in the liver. Cholesterol synthesis initially involves the conversion of acetate to mevalonic acid. The rate-limiting step is catalysed by enzyme beta-hydroxy-beta-methyl glutaryl coenzyme A reductase (HMGCoA reductase). HMGCoA reductase is the rate-limiting enzyme in cholesterol synthesis. The activity of HMGCoA reductase is controlled by negative feedback by the intracellular cholesterol concentration (cholesterol pool). 

(4) Storage of Cholesterol

About two-thirds of the plasma cholesterol is esterified with fatty acids to form cholesteryl esters (CE). Cholesteryl esters are storage forms of cholesterol. The active form of cholesterol is free cholesterol (FC).

(5) Determination of Plasma Cholesterol

Assays in routine use measure the plasma total cholesterol concentrations and do not distinguish between the unesterified and esterified forms. To obtain a measurement for CE separate from FC, HPLC will need to be used. HPLC is high-performance liquid chromatography - it separates the 2 forms of cholesterol (FC, CE) and they can then be determined separately.

When performing cholesterol screening, clinical cholesterol assays measure the Total Cholesterol (TC). Total Cholesterol is the sum of all the cholesterol in all the lipoproteins present in blood.

Unlike that of triglyceride, plasma concentration of cholesterol does not rise after a fatty meal. This means, the subject or patient (or you) does not have to fast 12 hours before a cholesterol test.

(6) High Plasma Cholesterol and Heart Disease

A high level of cholesterol in the blood is considered to be a risk factor for cardiovascular diseases. High blood serum cholesterol levels are associated with increased risk of cardiovascular diseases.

Cholesterol and lipoprotein levels can be normalized through exercise and dietary changes. Dietary changes include reduced Calorie diets that eliminate hydrogenated fats and add sources of polyunsaturated fatty acids (PUFA) such as grape seed oil. 

Blood cholesterol levels can be lowered by reducing the sources of dietary cholesterol, increasing the amount of fiber in the diet, and by consuming oils high in polyunsaturated fatty acids while reducing the intake of saturated fats.

Research on dietary fats by Hegsted and others has shown that myristic acid (C14:0), and palmitic acid (C16:0) increase cholesterol levels, whereas polyunsaturated fats such as linoleic acid (C18:2) reduce cholesterol levels. 

(7) Reduced Absorption of Cholesterol

Sterols of vegetable origin are called "phytosterols". They have the same basic structure as cholesterol, but differ in the side chains attached to carbon 17. Phytosterols, such as stigmasterol from soybean oil, are of current interest because they lower blood cholesterol levels. Sterols that are fully saturated (no double bonds) are called "stanols". For example, stigmastanol has the same structure as stigmasterol, but without the double bonds. When fatty acids react with the hydroxyl at carbon 3 they form "sterol esters".

References:
Clinical Chemistry in Diagnosis and Treatment. Sixth edition, 1994. Philip D Mayne. page 225
http://www.scientificpsychic.com/fitness/fattyacids2.html