Cholesterol fulfills three important functions in the body:

It is an indispensable component of all cell membranes of animals. These are wrappers that are essential to protect the cell from its external environment (extracellular) and therefore helps keep the internal environment of the cell (intracellular).

It is a precursor of steroid hormones synthesized in the ovaries, testes and adrenal glands. Steroid hormones regulate essential processes in the body, such as growth and development of sexual characteristics.

It is a precursor of bile acids, which are important in digestion and absorption of fats.

Cholesterol Sources

In general, cholesterol comes from two sources: exogenous (dietary) and endogenous (synthesized in the body).

Cholesterol in your daily diet is a substantial source of total cholesterol and may contribute up to 20% to 40% of total cholesterol in the body. The small intestine is the site of cholesterol uptake from the diet. The endogenous synthesis accounts for 60% to 80% of the cholesterol. It is commonly accepted that the liver produced the bulk of endogenous colesterol. However, recent research indicates that much of the cholesterol biosynthesis takes place in non-hepatic tissues. The liver itself represents the majority of the uptake of cholesterol from plasma.

Plasma cholesterol

Plasma cholesterol (ie, blood cholesterol) is derived from both the endogenous and the exogenous cholesterol. The following actions in the body affect the level of cholesterol in the bloodstream:

Cholesterol biosynthesis

The main precursor for the biosynthesis of cholesterol and other lipids such as triglycerides and fatty acids is acetyl-coenzyme A or acetyl-CoA. The conversion of acetyl-CoA to cholesterol takes place in a complex way that requires 30 separate reactions.

While the primary product of this pathway is cholesterol, also important end products are formed. Ubiquinone is part of the electron transport chain of energy metabolism and dolicol is a component of cell membranes. Cholesterol itself is a component of cell membranes and a precursor to steroid hormones (eg cortisol, aldosterone, testosterone and estrogen) and bile acids.

Early and limiting step in the biosynthesis of cholesterol

The first series of reactions in the pathway of biosynthesis of cholesterol from the series of acetyl-CoA to 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) – is common for the synthesis of cholesterol and other lipids . The next step, the conversion of HMG-CoA to mevalonic acid, or mevalonate (MVA), is catalyzed by an enzyme called HMG-CoA reductase. This enzyme is known as the limiting enzyme reaction because this is a bottleneck in the biosynthesis pathway. The conversion of HMG-CoA, the substrate of HMG-CoA reductase, is the so called early and limiting step in the biosynthesis of cholesterol. Para reducir la conversión de HMG-CoA a MVA, debe inhibirse la acción de la HMG-CoA reductasa. To reduce the conversion of HMG-CoA to MVA, the action of HMG-CoA reductase should be inhibited.

Like the early and limiting step in the biosynthesis of cholesterol, the passage of the HMG-CoA reductase has a considerable biological importance. Several physiological signals act at the level of HMG-CoA reductase to reduce or increase the synthesis of cholesterol, depending on the needs of the organism. Por ejemplo, un nivel alto de colesterol libre en los hepatocitos significa que está presente una cantidad suficiente de colesterol; en respuesta, se inhibe la actividad de la HMG-CoA reductasa y se sintetiza menos colesterol. For example, a high level of free cholesterol in the liver means that this is a sufficient amount of cholesterol, in response it inhibits the activity of HMG-CoA reductase and cholesterol synthesis less. This process not only affects the amount of liver cholesterol, but also the amount of cholesterol in blood. In the liver, even small decreases in the production of cholesterol lead to an increase in the production of LDL receptors that remove cholesterol from the blood.

By the action of the enzyme HMG-CoA reductase, HMG-CoA is converted into mevalonic acid (MVA).

Absorción de colesterol Cholesterol absorption

Cholesterol absorption takes place in the small intestine. Cholesterol available for absorption comes from three sources:

Sources

Quantity (%)

1. Cholesterol in bile (biliary cholesterol). 50%

2. Cholesterol in the diet (exogenous). 31%

3. Cholesterol in the scaly epithelial cells of the intestinal wall during normal cell turnover. 19%

Of total cholesterol available for absorption, 50% is absorbed through the intestinal wall and 50% is excreted in feces.

The mechanism by which cholesterol is absorbed from the intestine is complex and only partially understood. Studies suggest that cholesterol is emulsified by bile salts, wrapped in micelles and transferred to the brush border of the small intestine. After entering the enterocytes (cells in the intestinal mucosa). Once inside the cells, cholesterol is esterified (combined with a fatty acid) through the action of the enzyme called acyl-coenzyme A: cholesterol aciltransferasa (ACAT) and assembled into chylomicrons. These chylomicrons are secreted into the lymph and subsequently enter the blood. By inhibiting cholesterol absorption through the intestinal wall, ie by increasing the amount of cholesterol excreted, the amount of cholesterol entering the blood within these chylomicrons will be reduced.

Conclusion

Cholesterol fulfills three important functions in the body: it is an essential component of cell membranes of animals, is a precursor of steroid hormones and is a precursor of bile acids.

Cholesterol is derived from the diet (exogenous) and biosynthesis (endogenous).

Cholesterol in daily diet, bile and epithelial cells are absorbed through the small intestine. By inhibiting cholesterol absorption in the intestine plasma cholesterol can be reduced.

The limiting enzyme in the biosynthesis of cholesterol called HMG-CoA reductase catalyzes the conversion of HMG-CoA to mevalonic acid (mevalonate).

Tags: cholesterol, Nutrition

This entry was posted on Wednesday, August 5th, 2009 at 2:09 pm and is filed under Pharmaceutical. You can follow any responses to this entry through the RSS 2.0 feed. You can leave a response, or trackback from your own site.