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Understanding Lipoprotein Metabolism
Sep 6, 2024
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Lecture Notes: Lipoprotein Metabolism
Overview
Lipoprotein metabolism consists of two pathways:
Exogenous Pathway
: Transports dietary cholesterol and triglycerides to tissues.
Endogenous Pathway
: Transports cholesterol and lipids synthesized in the body.
Exogenous Pathway
Focus on the small intestine where dietary lipids are processed:
Triglycerides and cholesterol (free and esters) are present.
Chemoreceptors
in the enteric system detect fats and stimulate enteroendocrine cells to release cholecystokinin (CCK).
CCK affects the gallbladder, leading to bile release.
Bile and Emulsification
Bile contains:
Cholesterol, phospholipids, water, electrolytes
Bilirubin (pigment) and bile salts (e.g., colic acid, deoxycolic acid)
Bile salts emulsify fats, breaking down large fat globules into smaller droplets.
This process enhances the effectiveness of pancreatic lipase in breaking down triglycerides into free fatty acids and monoglycerides.
Lipid Absorption
Bile salts surround and stabilize lipid droplets, forming micelles (500x smaller than emulsion droplets).
Micelles transport fats towards enterocytes where absorption occurs.
Inside enterocytes:
Free fatty acids and monoglycerides are reassembled into triglycerides within the smooth endoplasmic reticulum.
Triglycerides are combined with ApoB48 protein and phospholipids to form
chylomicrons
.
Chylomicrons
Transport in lymphatic system via lacteals.
Enter bloodstream and acquire additional proteins from HDL:
ApoE and ApoC2 are added.
ApoC2 activates lipoprotein lipase (LPL) in capillaries, releasing free fatty acids and glycerol.
Free fatty acids are used for energy in muscles or stored in adipocytes.
Chylomicron Remnants
After unloading triglycerides, chylomicrons become remnants.
Remnants are absorbed by the liver via LDL receptors (and other receptors like LRP).
Cholesterol from remnants can be:
Converted into bile salts, stored as cholesterol esters, or incorporated into cell membranes.
Endogenous Pathway
Liver synthesizes
VLDL
from triglycerides and cholesterol.
VLDL also acquires ApoE and ApoC2 from HDL.
VLDL delivers triglycerides to tissues, becoming IDL (intermediate density lipoprotein) and then LDL (low density lipoprotein).
VLDL Remnants (IDL)
Can be returned to liver or converted to LDL.
Involves hepatic triglyceride lipase reducing triglyceride content.
LDL predominantly carries cholesterol to tissues.
LDL and Atherogenesis
LDL is known as "bad cholesterol" due to its role in atherosclerosis.
Can be oxidized, leading to uptake by macrophages and foam cell formation, contributing to plaque development.
HDL: The "Good Cholesterol"
HDL (high-density lipoprotein) helps remove cholesterol from tissues and transports it back to the liver.
Functions via scavenger receptors and donates ApoE and ApoC2 to other lipoproteins.
Aids in cholesterol ester transfer and converts cholesterol to cholesterol esters for storage.
Summary of Lipoproteins and Their Components
Chylomicrons
: Mainly carry triglycerides, about 1% protein.
VLDL
: About 10% protein, carry triglycerides and cholesterol.
IDL
and
LDL
: Intermediate and low-density, carry more cholesterol.
HDL
: Highest protein (20%), aids in reducing cholesterol.
Blood Cholesterol Levels
Total cholesterol should be <200 mg/dL.
HDL: Higher levels are better (40-60 mg/dL for males and females respectively).
LDL: Lower levels are preferred (<100 mg/dL).
Conclusion
Understanding lipoprotein metabolism is crucial for managing cardiovascular health.
Regular lipid panels can help monitor and manage cholesterol levels effectively.
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