Human Biochemistry, Volume 1 - Murray R. 1993

Bioenergetics and Carbohydrate and Lipid Metabolism
Transport and Storage of Lipids
Plasma Lipoprotein Metabolism - Formation of Chylomicrons and Very Low-Density Lipoproteins (VLDL)

By definition, chylomicrons are located in the chyle, which is formed exclusively within The Lymphatic system of the intestinal villi. Chyle also contains smaller and denser particles that share the same physical characteristics as VLDL. However, the apolipoprotein composition of these particles resembles that of chylomicrons rather than VLDL, and therefore they should be classified as small chylomicrons. Chylomicrons are formed even during fasting, accounting for The transport of 50% of Lymph triacylglycerols and Cholesterol; the Lipids required for their synthesis are derived primarily from Bile and intestinal secretions. At the same time, the number of chylomicrons increases during the absorption of dietary triacylglycerols following a meal. The majority of plasma VLDL are synthesized in The Liver and are responsible for transporting triacylglycerols from the liver to other Tissues.

The mechanisms of chylomicron formation in intestinal Cells and VLDL production in hepatic parenchymal cells share many common features (Fig. 26.3). Apolipoprotein B is synthesized by Ribosomes in the rough Endoplasmic reticulum and incorporated into Lipoproteins within the smooth endoplasmic reticulum, which serves as the primary site of triacylglycerol synthesis. The lipoproteins then pass through the Golgi apparatus, where carbohydrate residues are believed to be attached to the lipoprotein molecule. Chylomicrons and VLDL are released from intestinal and hepatic cells through the fusion of secretory vesicles with The Cell membrane (reverse pinocytosis). From intestinal cells, chylomicrons enter the intercellular spaces and subsequently the Lymphatic vessels of the intestinal villi—the lacteals—to be transported via the lymph. VLDL are secreted by hepatic parenchymal cells first into the space of Disse and then through fenestrations between endothelial cells into the hepatic sinusoidal capillaries. The similarity between the formation mechanisms of chylomicrons and VLDL is remarkable; aside from mammary gland cells, only intestinal and hepatic cells are capable of secreting emulsified lipids. The fact that lipoproteins the size of chylomicrons and VLDL cannot cross the endothelial cells of Blood Vessels unless hydrolyzed is presumably why dietary fats pass from the intestine into the bloodstream via the lymphatic pathway (the Thoracic duct) rather than through the PORTAL VEIN SYSTEM.

Chylomicrons and VLDL isolated from blood contain apolipoproteins C and E, whereas newly secreted (nascent) lipoproteins contain very low amounts of these apolipoproteins or lack them entirely. It appears that apolipoproteins C and E are transferred from HDL to chylomicrons and VLDL after the latter enter the bloodstream (Figs. 26.4 and 26.5). The factors regulating VLDL secretion by hepatic cells are discussed in greater detail below.

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Fig. 26.3. Formation and secretion of (A) chylomicrons by an intestinal cell and (B) very-low-density lipoproteins by a hepatic cell. RER — rough endoplasmic reticulum; SER — smooth endoplasmic reticulum; G — Golgi apparatus; N — Nucleus; Ch — chylomicron; VLDL — very-low-density lipoprotein; En — endothelium; DS — space of Disse filled with Blood Plasma. The diagram schematically illustrates The sequence of processes that can be observed using an Electron microscope.

Fig. 26.4. Metabolic fate of chylomicrons. Apo-A — apolipoprotein A; Apo-B — apolipoprotein B; Apo-C — apolipoprotein C; Apo-E — apolipoprotein E; HDL — high-density lipoprotein; TG — triacylglycerol; Ch — cholesterol and its esters; PL — phospholipid. Only the predominant lipids are indicated.

Fig. 26.5. Metabolic fate of very-low-density lipoproteins (VLDL) and The formation of low-density lipoproteins (LDL). Apo-A — apolipoprotein A; Apo-B — apolipoprotein B; Apo-C — apolipoprotein C; Apo-E — apolipoprotein E; HDL — high-density lipoprotein; TG — triacylglycerol; IDL — intermediate-density lipoprotein; Ch — cholesterol and its esters; PL — phospholipid. Only the predominant lipids are indicated. There is ongoing debate regarding the pathway by which IDL enter hepatic cells: via apolipoprotein E receptors or LDL receptors.

Apolipoprotein B is an essential component in the formation of chylomicrons and VLDL. In the rare disorder abetalipoproteinemia, apolipoprotein B is not synthesized and, consequently, lipoproteins containing this apolipoprotein fail to form; As a result, lipid droplets accumulate within intestinal and hepatic cells.