Metabolism of lipids and lipoproteins
Chylomicrons
Chylomicrons (particles very rich in triacylglycerols) are formed in the cells of the Small Intestine mucosa by absorption of dietary fat. The condition for the secretion of chylomicers from the cisterna Golgi apparatus of enterocytes is the presence of apolipoprotein B48 (=ApoB48). This apolipoprotein contains only 48% of the peptide molecule of liver apolipoprotein, which is therefore referred to as ApoB100 (i.e. 100% peptide chain).
After 12-14 hours of fasting, chylomicrons are no longer normally present in the blood plasma. They are immediately hydrolyzed upon entering the blood capillary bed by the action of endothelial lipoprotein lipase (LPL) to form chylomicron remnants (chylomicron remnants). During the lipolytic action of these enzymes, fatty acids are released.
Some components of chylomicrons (apoA-I, apoA-II, apoC, and phospholipids) are transferred to HDL particles, and other components (apoE and cholesterol esters) are transferred from HDL to chylomicrons. Chylomicron remnants containing apoB48 and apoE are taken up by their receptors in the liver. The formation of these receptors in liver tissue cells is regulated by the amount of cholesterol and fat in the diet. Their activity decreases with age. ApoE facilitates the uptake of chylomicron debris, while apo C-III inhibits this process. The physiological importance of chylomicrons lies in the delivery of fatty acids from food to adipocytes and muscle cells.
VLDL
VLDL synthesis occurs in the liver and is more intense in obese individuals. It is regulated in part by diet and hormones and is inhibited by uptake of chylomicron debris in the liver. By the action of lipoprotein lipase (LPL) located on the membrane of endothelial capillaries, with the participation of apoC-II as a cofactor, triacylglycerols carried by VLDL particles are hydrolyzed to be available in the respective cells as an energy source or for storage in the form of storage triacylglycerols. In this process, some components from VLDL (apoE, apoC) are transferred to HDL, while apoB100 remains on VLDL-remnants (VLDL-remnants or intermediate lipoprotein particles = IDL). The final product of VLDL catabolism is LDL.
Under pathological conditions (in some patients with severe hypertriacylglycerolemia), VLDL are removed from the blood plasma without being converted into LDL particles. The liver produces different types of VLDL-particles: On a low-fat diet, these are particles of Sf 60-400, which are larger and non-atherogenic; with a diet rich in fats, mainly small dense VLDL with Sf 12-60 are formed, which, on the other hand, are very atherogenic., small dense LDL-B is formed from them.
The receptor for lipoprotein "remnants" (VLDL remnants and chylomicron remnants) is the so-called protein related to the LDL receptor (=LDL receptor related protein). The specific ligand is Apo E Lipoprotein lipase (=LPL), which catalyzes the cleavage of fatty acids from triacylglycerols in chylomicrons and VLDL, is in the surface part of endothelial capillaries mainly in adipose tissue and muscle, where it is necessary for the formation of storage triacylglycerols and for the utilization of fatty acids as an energy source. The activator is Apo CII. Insulin does not directly affect LPL activity but is needed to maintain it. On the other hand, the so-called hormone-sensitive lipase (=HSL), which hydrolyzes intracellular triacylglycerols (released fatty acids enter the blood circulation and linked to albumin to the liver), is influenced by insulin directly, in the sense of inhibition. Glucagon, on the other hand, stimulates its activity. Thus, after a meal, insulin supports the storage of fatty acids in adipocytes, and conversely, during starvation, they are released into the circulation and absorbed in the liver and muscles.
LDL
LDL are the main particles that carry cholesterol in the blood plasma. The largest part comes from the transformation of VLDL, but some is synthesized directly (especially in patients with familial hypercholesterolemia). The main protein component of LDL is apoB100. LDL can be catabolized by different cell types, both by an ``LDL-receptor-dependent mechanism and by an LDL-receptor-independent mechanism ("scavenger" mechanism).
After binding to the membrane receptor (its duration is 5-7 minutes), the LDL particle is internalized and broken down by the cell. The resulting free cholesterol inhibits the activity of 3-hydroxy-3-methylglutaryl-CoA-reductase, which is a key enzyme for the synthesis of (de novo) cholesterol in the cell. In this way, "cholesterol synthesis is controlled according to the needs of the cells". LDL not captured by peripheral cell receptors (about one third) are catabolized by "sweeping" (=scavenger) cells. However, this method is not driven by the needs of the cells. Some LDL is also metabolized in the liver. The released cholesterol is either catabolized to bile acids and excreted into the bile, or is reused for lipoprotein synthesis.
'Oxidized LDL particles are "pathological" particles, strongly atherogenic,
