All cells require lipids (fats) to synthesize membranes and provide energy. Lipids are transported in the blood as lipoproteins. These small particles consist of a core of triglycerides and cholesteryl esters, surrounded by a coat of phospholipids, cholesterol and proteins termed apolipoproteins or apoproteins. Apoproteins stabilize the lipoprotein particles and help target specific types of lipoproteins to various tissues. Hyperlipidaemias are abnormalities of lipoprotein levels which promote the development of atherosclerosis (see Chapter 37) and coronary heart disease (CHD; see Chapters 40–42).

Lipoproteins and Lipid Transport

Figure 36 illustrates pathways of lipid transport in the body. The exogenous pathway (left side of Figure 36) delivers ingested lipids to the body tissues and liver. Ingested triglycerides and cholesterol are transported by the protein Niemann–Pick C1-like 1 (NPC1L1) into the mucosal cells lining the intestinal lumen, which combine them with apoprotein apo B-48, forming nascent chylomicrons which are secreted into the lymph, pass into the bloodstream, and combine with apo E and apo C-II to become chylomicrons. These bind to the capillary endothelium in muscle and adipose tissue, where apo CII activates the endothelium-bound enzyme lipoprotein lipase (LPL) which hydrolyses the triglycerides to fatty acids which enter the tissues. The liver takes up the residual chylomicron remnants. These are broken down to yield cholesterol, which the liver also synthesizes. The rate-limiting enzyme in hepatic cholesterol synthesis is hydroxy-methylglutaryl coenzyme A reductase (HMG-CoA reductase). The liver uses cholesterol to make bile acids. These pass into the intestine and act to solubilize dietary cholesterol so it can be absorbed via NPC1L1. Bile acids are almost entirely reabsorbed and returned to the liver, although about 0.5 g/day is lost in the faeces, providing a path by which the body excretes cholesterol.

The endogenous pathway cycles lipids between the liver and peripheral tissues. The liver forms and secretes nascent very low density lipoproteins (VLDLs), consisting mainly of triglycerides with some cholesterol and apo B-100, into the lacteal vessels. These acquire apo E and apo C-II from HDL in the plasma to become VLDL. As with chylomicrons, apo C-II activates LPL causing VLDL triglyceride hydrolysis and provision of fatty acids to body tissues. As it is progressively drained of triglycerides, VLDL becomes intermediate density lipoprotein (IDL) and then low-density lipoprotein (LDL), losing all of its apoproteins (to HDL) except for apo B-100 in the process. Most of the LDL, which contains mainly cholesteryl esters (CE), is taken up by the liver; the rest serves to distribute cholesterol to the peripheral tissues. Cells regulate their cholesterol uptake by expressing more LDL receptors (which bind to apo B-100) when their cholesterol requirement increases.

Cholesterol is removed from tissues by high-density lipoprotein (HDL). HDL is initially assembled in the plasma from lipids and apoproteins (mainly apo A1,

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