Page last updated: 2024-10-24

chylomicron remodeling

Definition

Target type: biologicalprocess

The acquisition, loss or modification of a protein or lipid within a chylomicron, including the hydrolysis of triglyceride by lipoprotein lipase and the subsequent loss of free fatty acid. [GOC:BHF, GOC:expert_pt, GOC:mah, GOC:rl]

Chylomicron remodeling is a crucial step in the digestion and transport of dietary lipids. It involves a series of enzymatic modifications that transform nascent chylomicrons, which are large triglyceride-rich lipoproteins assembled in the intestinal cells, into smaller, more metabolically active particles. Here's a detailed description of the process:

1. **Nascent Chylomicron Formation:** After dietary fats are digested in the small intestine, they are absorbed into the intestinal cells and packaged into nascent chylomicrons. These particles consist of a core of triglycerides surrounded by a phospholipid monolayer containing apolipoproteins, mainly apoB-48.

2. **Initial Remodeling in the Lymphatics:** As nascent chylomicrons enter the lymphatic system, they encounter lipoprotein lipase (LPL) anchored to the endothelial cells lining the lymphatic vessels. LPL hydrolyzes triglycerides in the chylomicron core, releasing free fatty acids (FFAs) and glycerol. These FFAs are then taken up by surrounding tissues, primarily muscle and adipose tissue, for energy utilization or storage.

3. **Chylomicron Remnant Formation:** As triglycerides are hydrolyzed by LPL, the chylomicron size decreases, and its density increases. The remnants now have a higher concentration of cholesterol esters and apolipoproteins, including apoE.

4. **Hepatic Lipase and Cholesterol Metabolism:** Chylomicron remnants circulate in the blood and encounter hepatic lipase (HL) in the liver. HL further hydrolyzes remaining triglycerides, and the remnants become enriched in cholesterol esters. The remnants also interact with hepatic receptors, particularly the LDL receptor (LDLR) and scavenger receptor B1 (SR-B1), which mediate the uptake of cholesterol esters into the liver.

5. **Cholesterol Ester Transfer Protein (CETP):** Chylomicron remnants can also interact with CETP, a protein that facilitates the transfer of cholesterol esters from chylomicrons to high-density lipoproteins (HDLs). This transfer contributes to the reverse cholesterol transport pathway, which helps remove excess cholesterol from peripheral tissues.

6. **Endocytosis and Intracellular Degradation:** Finally, chylomicron remnants are taken up by the liver through endocytosis and undergo intracellular degradation. This process releases free cholesterol, fatty acids, and amino acids, which are then utilized by the liver for various metabolic functions.

The remodeling process ensures efficient delivery of dietary lipids to various tissues while minimizing the risk of high levels of circulating triglycerides, which can have adverse health effects. The process is tightly regulated by various factors, including hormones, dietary composition, and genetic factors, ensuring optimal lipid metabolism and overall health.'
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Proteins (1)

ProteinDefinitionTaxonomy
Lipoprotein lipaseA lipoprotein lipase that is encoded in the genome of human. [PRO:DNx, UniProtKB:P06858]Homo sapiens (human)

Compounds (2)

CompoundDefinitionClassesRoles
orlistatorlistat : A carboxylic ester resulting from the formal condensation of the carboxy group of N-formyl-L-leucine with the hydroxy group of (3S,4S)-3-hexyl-4-[(2S)-2-hydroxytridecyl]oxetan-2-one. A pancreatic lipase inhibitor, it is used as an anti-obesity drug.

Orlistat: A lactone derivative of LEUCINE that acts as a pancreatic lipase inhibitor to limit the absorption of dietary fat; it is used in the management of obesity.
beta-lactone;
carboxylic ester;
formamides;
L-leucine derivative
anti-obesity agent;
bacterial metabolite;
EC 2.3.1.85 (fatty acid synthase) inhibitor;
EC 3.1.1.3 (triacylglycerol lipase) inhibitor
xen445