Triacylglycerol Transport by Chylomicrons
Chylomicrons and LDs share common features, such as low circulating lipids and fat-soluble vitamins, as well as early childhood failure to thrive, ataxic neuropathy, and visual impairment. Understanding the molecular dynamics of these particles can help physicians identify additional indications for treatment. The transport of triacylglycerols by chylomicrons is a critical component of this particle.
Mechanisms of chylomicron formation
The ER lumen is a complex environment in which chylomicron biogenesis occurs. In a two-step process, newly synthesized apolipoprotein B48 is chaperoned by a luminal protein, MTP, and transported into the rough endoplasmic reticulum (RE). ApoB can associate with dense particles that contain mostly phospholipids and cholesterol, but also contains small amounts of triacylglycerol. Without association with dense particles, apoB can be destroyed.
Although we know that lipids and amino acids are transported into the central lacteal, we still do not fully understand how large chylomicrons gain access to the central lacteal. It is thought that specialized “button junctions” in lacteal patches make them more permeable to chylomicrons. After disassembling, bloodborne chylomicrons are used throughout the body.
In addition to dietary triglycerides, microsomal triglyceride transfer protein is involved in chylomicron assembly. Cholesterol is synthesized from bile, and ApoB48 reassembles them into chylomicrons. During chylomicron synthesis, cholesterol is esterified using acylcoenzyme A:cholesterol acyltransferase. Similarly, fatty acids are reconverted back into triglycerides.
The intestine plays a critical role in lipoprotein production. The production of these particles is essential for the absorption of dietary fats and fat-soluble vitamins. It starts with the formation of primordial phospholipid-rich particles in the endoplasmic reticulum. Next, the particles travel to the Golgi for secretion. The villus enterocytes secrete lipids that are subsequently hydrolyzed by lipoprotein lipase.
Models of chylomicron assembly
The basic events in chylomicron assembly are similar to those in VLDL assembly, but the molecular details of the process are distinct. For this reason, we can use adult rabbit enterocytes as a model system for examining the processes involved in fat absorption. A key component of chylomicron assembly is the accumulation of apoB-48, which is a non-essential lipid found exclusively in chylomicrons.
The endocytic pathway of lipoprotein production starts in the endoplasmic reticulum and begins with the formation of primordial phospholipids-rich particles, which are then transported to the Golgi for secretion. Several classes of transporters play critical roles in selectively absorbing lipids from the food we eat and secrete them. Cholesterol-rich lipoproteins are metabolized by Lipoprotein lipase, which catalyzes a process that releases triglycerides and transports them into the blood.
After leaving the ER, most of the TAG that will eventually enter the chylomicron forms a lipid aggregate in the ER mediated by MTP. MTP transports newly synthesized apolipoprotein B48 to the rough endoplasmic reticulum, where it is chaperoned by the luminal protein MTP. The newly synthesized apoB then associates with dense particles of cholesterol, phospholipids, and triacylglycerol. Unless it associates with these particles, apoB is destroyed.
Transport of triacylglycerols by chylomicrons
Chylomicrons are particles produced by the lymphatic system that drain the intestine. These particles transport dietary lipids into circulation. Chylomicrons also contain small amounts of VLDL, although most VLDL in plasma is derived from hepatic sources. Both types of lipoproteins transport triacylglycerols between the liver and extrahepatic tissues.
Chylomicrons contain different molecules, such as cholesterol and apolipoprotein E. Cholesteryl ester is a phospholipid that is found in high-density lipoproteins. Chylomicrons are produced in the gastrointestinal tract and move to the lymphatic system. Chylomicrons are disassembled in the bloodstream, where they are used throughout the body.
When examining chylomicron mobility, it is important to remember that chylomicrons tend to clump when they enter plasma. Chylomicron mobility is governed by their ability to migrate with alpha and beta globulins. Nevertheless, the lipids themselves are relatively stable during repeated washing. Chylomicrons are a form of lipoprotein that is similar to crz-globulins.
Chylomicrons are synthesized from dietary fat. VLDL and HDL are made by chylomicrons and transport triacylglycerols. HDL is responsible for the removal of bad cholesterol from tissues. These lipoproteins are often referred to as “good” cholesterol, but it should be noted that VLDL is more prone to deposit into blood vessels.