Chylomicrons

These lipoproteins are named as chylomicrons since they are drained into chyles in the lymphatic system and their size is about one micron in diameter.

Figure 1: Schematic diagram of chylomicron.

Synthesis - They are synthesized in the epithelial cells (enterocytes) of small intestines. The lipid components are synthesized from the absorbed dietary fatty acids and glycerol. The apolipoproteins (apoB48 and apoA)   are synthesized in the rough endoplasmic reticulum by the ribosomes. The lipids are assembled with apolipoproteins in the glogi apparatus and then packed into the secretory vesicles and they are secreted by exocytosis into the intercellular space. The chylomicrons in these forms are known as nascent chylomicrons. They are then are drained into lacteals, and through the thoracic duct enter into venous circulation where they receive apoC and apoE from HDL to become the mature chylomicrons.

Figure 2: The formation and secretion of chylomicrons by an intestinal cell. (C, chylomicrons; E, endothelium; G, Golgi apparatus; N, nucleus; RER, rough endoplasmic reticulum; SER, smooth endoplasmic reticulum; Apolipoprotein B, synthesized in the RER, is incorporated into particles with triacylglycerol, cholesterol, and phospholipids in the SER. After the addition of carbohydrate residues in G, they are released from the cell by reverse pinocytosis. Chylomicrons pass into the lymphatic system.

Structure - These lipoproteins consist of about 2% proteins, i.e., apoB48, apoA. apoC and apoE and about 98% lipids, mainly triglycerides.

Fate - The mature chylomicrons in the peripheral tissues such as adipose tissue, skeletal and cardiac muscles are acted upon by the plasma enzyme lipoprotein lipase (LPL) that are activated by apoC II, present anchored with the heparin sulfate to the capillary endothelium of these tissues.

Figure 3: Binding of a chylomicron to lipoprotein lipase to the inner surface of a capillary. The chylomicron is anchored by lipoprotein lipase, which is linked by a polysaccharide chain to the lumenal surface of the endothelial cell. When activated by apoprotein C-II, the lipase hydrolyzes the triacylglycerols in the chylomicron, allowing uptake into the cell of the glycerol and the free fatty acids.

This enzyme action hydrolyses the triglycerides into the free fatty acids and glycerol. The free fatty acids are taken up by the cells in these tissues are either used in energy production in the skeletal and cardiac muscle tissues or are used in synthesis of fat in adipocytes for storage to be used later or to produce milk in lacteals in the mammary glands of breast feeding women. These lipoprotein lipases are also known as the clearing factors as they clears the turbidity due to chylomicrons in plasma. Upon losing most of their lipid contents as triglycerides to these peripheral tissues, they return their apoA and apoC back to the HDL and become what os known as chylomicron remnants. These remnants further gives remaining of their lipids as triglycerides to HDL in exchange for the cholesterol esters by means of the enzyme known as cholesteryl ester exchange protein (CEPT), also called as apoD. Finally the chylomicron remnants are recognized by the liver through their apoE, and get internalized by endocytosis into these hepatocytes with their receptors on the surface. They get fused with the lysozomes. The apoproteins are hydrolyzed into amino acids and the lipids into cholesterol and fatty acids for reuse or disposal. Normally, chylomicrons are undetected in plasma in the fasting state (>12 hours after meals). They form a white creamy layer floating on the surface of plasma after a fatty meal.

Figure 4: Metabolic fate of chylomicrons. (A, apolipoprotein A; B-48, apolipoprotein B-48; C, apolipoprotein  C; C, cholesterol and cholesteryl ester; E, apolipoprotein E; HDL, high-density lipoprotein; HL,hepatic lipase; LRP, LDL-receptor-related protein; PL, phospholipid; TG, triacylglycerol.) Only the predominant lipids are shown.

References:   1. Harper's Illustrated Biochemistry, 30E, 2015

                      2. Mathew’s Biochemistry, 4E, 2013