Biosintesis De Colesterol y Esteroides (Ingles)

Biosynthesis of Cholesterol and Steroids
INTRODUCTION |

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Cholesterol is one molecule with many functions. It is a lipid that is an essential component of mammalian cell membranes. It is also the most abundant sterol. Cholesterol is the precursor of three important classes of biologically active compounds: the bile acids, the steroid hormones, and vitamin D. Cholesterol metabolism isimportant in the etiology of cardiovascular disease, and it is a major component of gall stones. |

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The typical daily Western diet contains approximately 500 mg (1.2 mmol) of cholesterol daily, mainly in meat, eggs, and dairy products (see Chapter 21). Under normal circumstances, 30-60% of this is absorbed from the gut. |

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After absorption, cholesterol is transported to theliver and to peripheral tissues in the form of chylomicrons. The liver repackages it into another lipoprotein, VLDL (see Chapter 17 and Table 17.3). VLDL subsequently transforms into VLDL remnants (or IDL) and then into LDL. VLDL remnants and LDL can deliver cholesterol to tissues by binding to the apoB/E receptor (LDL receptor). |

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The sterol ring of cholesterol cannot be degraded in thehuman body. Therefore it is excreted either in the free form as the biliary cholesterol, or in the form of bile acids. Most of the bile acids are however returned to the liver after reabsorption in the terminal ileum. This is known as the enterohepatic circulation. |

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Human beings synthesize 1g cholesterol each day, mainly in the liver. The rate of its endogenous synthesis isdetermined by dietary intake. For this reason both dietary intake and biosynthesis are important in determining its plasma concentration. |
CHOLESTEROL STRUCTURE |

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The structure of cholesterol is shown in Figure 16.1. It has a molecular weight of 386 Da and contains 27 carbon atoms, of which 17 are incorporated into four fused rings (the perhydrocyclopentano-phenanthrene nucleus), two are inangular methyl groups attached at the junctions of rings AB and CD and eight are in the peripheral side chain. Cholesterol is almost entirely composed of carbon and hydrogen atoms; there is a solitary hydroxyl group attached to carbon atom 3. It is also almost completely saturated, having just one double bond between carbon atoms 5 and 6. In three-dimensional terms the ring structure ofcholesterol is approximately planar. |
THE FREE AND ESTERIFIED CHOLESTEROL |

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Its structure gives cholesterol a low solubility in water. Only about 30% of circulating cholesterol occurs in the free form, the majority is esterified through the hydroxyl group to a wide range of long-chain fatty acids including oleic and linoleic acids. Cholesterol esters are even less soluble in water than freecholesterol and so it is perhaps surprising to discover cholesterol circulating in plasma in concentrations of about 5 mmol/L (200 mg/dL). The apparent paradox is explained by the presence of a range of lipoproteins which incorporate and thereby solubilize the cholesterol molecule (see Chapter 17). Within these lipoproteins, the hydrophobic cholesterol esters are located in the core of themolecule, with free cholesterol in the outside layer. |
The dietary cholesterol brought to the liver is mostly in the form of free cholesterol. On the other hand, the cholesterol present in VLDL and LDL is mostly in the form of cholesteryl esters. Esters are also the tissue storage form of cholesterol (they are stored in lipid droplets). In the plasma, cholesterol is esterified by the enzymecholesterol-lecithin acyltransferase (Chapter 17) and in the cells by the acyl-CoA: cholesterol acyltransferase (ACAT, now renamed SOAT) by reacting with fatty acyl-CoA. There are two isoforms of the ACAT present in the endoplasmic reticulum. Sixty to eighty percent of cholesteryl esters present in plasma are taken up by the liver.
CHOLESTEROL BIOSYNTHESIS |

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Acetyl-coenzyme A is the...