Liver cholesterol synthesised

Cholesterol is an extremely important biological molecule that modulates the fluidity of animal cell membranes and is the precursor of steroid hormones (such as progesterone, testosterone, oestradiol and cortisol) and bile acids. Cholesterol is either derived from the diet or synthesised de novo. Regardless of the source, cholesterol is transported through the circulation in lipoprotein particles, as are cholesterol esters, the cellular storage form of cholesterol. The amount of cholesterol synthesised daily in the liver of a normal person is usually double that obtained from dietary sources. Other sites of cholesterol synthesis include the intestine, and the degree of production is highly responsive to cellular levels of cholesterol. Over 1.2 g of cholesterol is lost in the faeces daily in the form of free sterol or as bile acids. 

About 1 g of cholesterol is ingested by adults each day in developed countries. A similar amount enters the lumen via the bile, synthesised from acetyl-CoA in the liver, is also released from sloughed epithelial cells. Absorption of cholesterol also occurs from the mixed micelles. Within the enterocyte, it is esterified and the cholesterol ester is incorporated into the chylomicrons. 

C24 bile acids are synthesised in the liver from cholesterol. The bacterial enzyme 7-a dehydroxylase converts CDCA into LCA and converts CA into DCA. UDCA a tertiary bile acid is also shown. 

The transport of lipids and cholesterol is accomplished by packaging them into lipoprotein complexes this is undertaken by both hepatocytes and enterocytes. Dietary triacylglycerols and cholesterol are packaged by enterocytes into chylomicrons, whereas de novo synthesised triacylglycerols in the liver are packaged in very low-density lipoproteins (VLDLs). 

Solubilisation (or emnlsification) of dietary lipids is accomplished by means of bile salts, which are synthesised from cholesterol in the liver and then stored in the gallbladder they are emptied into the gnt following the ingestion of fat. Emulsification of dietary fats renders them accessible... 

HDLs are synthesised de novo in the liver and small intestine, as primarily protein-rich particles. Newly formed HDLs are essentially devoid of cholesterol and cholesteryl esters. The primary apoproteins of HDLs are apo-A-I, apo-C-I, apo-C-II and apo-E. One major function of HDLs is to act as circulating stores of apo-C-I, apo-C-II and apo-E. 

HDLs gradually accumulate cholesteryl esters, converting nascent HDLs to HDL2 and HDL3. Any free cholesterol present in chylomicron remnants and VLDL remnants (IDLs) can be esterifled through the action of the HDL-associated enzyme, lecithin cholesterol acyltransferase (LCAT). LCAT is synthesised in the liver and so named because it transfers a fatty acid from the C-2 position of lecithin to the C-3-OH of cholesterol, generating a cholesteryl ester and lysolecithin. The activity of LCAT requires interaction with apo-A-I, which is found on the surface of HDLs. 

Figure 5.6 General scheme of lipoprotein metabolism. Triacylglycerols and cholesterol are exported from the liver in VLDLs, containing apolipoprotein B-lOO they further acquire apo-C-I, II, III and apo-E from circulating HDL. Apo-C-II activates lipoprotein lipase to remove fatty acids from VLDLs. As triacylglycerols are removed, VLDLs transform to IDEs and finally LDLs. LDLs are the main vehicle for transfer of cholesterol to the tissues uptake of LDL occurs primarily in the liver through LDL-receptor-mediated endocytosis, which requires the presence of apo-B-100. HDLs are synthesised essentially devoid of cholesterol or triacylglycerol and provide a circulating source of apo-C-I, II and apo-E. HDLs gradually accumulate cholesteryl esters, eventually returning these to the liver, mediated by an apo-A-I receptor this is referred to as reverse cholesterol transport. ...

HDL is synthesised and secreted from the liver and gut and aids the removal of cholesterol from peripheral tissues. It opposes the effects of LDL and protects against coronary heart disease. HDL is the substrate for LCAT, which converts the cholesterol in circulating plasma lipoproteins to cholesterol esters, which are then transferred to other lipoprotein particles. This is termed reverse cholesterol transport. Table... 

Mitochondria cannot synthesise GSH (see below). Thus, the mitochondrial GSH pool comes from cytosol GSH through a mitochondrial carrier. This GSH transporter identified in rat liver mitochondria is different from the canalicular and the sinusoidal carriers [68]. Chronic ethanol feeding impairs the mitochondrial GSH transport leading to mitochondrial GSH depletion [69]. An increase in microviscosity of mitochondrial membranes due to high cholesterol content appears to account for this impairment in GSH transport [70]. 

As reported in the Figure 29, fat is absorbed and packaged as chylomicrons (CM), and lipoprotein lipase (LPL) releases TG to yield the CM remnants. Very low density lipoproteins (VLDL) synthesised by the liver are broken down by LPL to yield intermediate density lipoprotein (DDL) and ultimately low-density lipoprotein (LDL). High-density lipoprotein clears cholesterol from the cell through lecithin-cholesterol acyltransferase (LCAT). 

Cholesterol is synthesised from glucose by the liver (Chapter 38). Some of the cholesterol is esterifled with fatty acids in a reaction catalysed by acyl CoA-cholesterol-acyl transferase (ACAT) to form cholesteryl ester (Fig. 39.2). This is hydrophobic and with its hydro-phobic associate, the triacylglycerols, is stored in the core of the nascent VLDL particles. The nascent VLDLs leave the Ever via the hepatic vein and progress to the periphery. In the peripheral capillaries, lipoprotein lipase removes much of the triacylglycerol content by... 

The bile acids are synthesised from cholesterol and this constitutes the major end point of cholesterol metabolism. Under physiological conditions the acids exist as salts. They are produced in the liver, stored in the gall bladder and secreted into the upper small intestine. They are important in several ways ... 

Cholic add is synthesised and esterified in the liver. Its precursors are obscure, and probably form part of the system whereby cholesterol is manufactured in the organism. 

The liver possesses the power of synthesising both cholesterol and cholic acid, and thus controls the amount of these substances present in the bile. Under normal conditions the amount of cholic acid produced synthetically is probably small, because the bile salts are almost completely reabsorbed from the intestine and return to the liver. 

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