Lipid Digestion and Transport PDF

# Lipid Digestion and Transport ## Digestion and Absorption - Dietary lipids include: triacylglycerol (TAG), cholesterol (C), cholesterol esters (CE), and phospholipids (PL). These lipids enter the stomach largely intact. - The main function of the stomach is to hydrolyze medium and short-chain fat...

# Lipid Digestion and Transport ## Digestion and Absorption - Dietary lipids include: triacylglycerol (TAG), cholesterol (C), cholesterol esters (CE), and phospholipids (PL). These lipids enter the stomach largely intact. - The main function of the stomach is to hydrolyze medium and short-chain fatty acids from the sn-3 position in TAG by the action of lingual and gastric lipase. - The small intestines act on TAG, DAG, C, CE, and PL, where they interact with bile salts to form micelles. - Free fatty acids, glycerol, monoacylglycerol (MAG), lysophospholipid, C, and Long-chain FA are absorbed into intestinal cells. - Short-and medium-chain free fatty acids do not get incorporated into micelles for absorption into the intestinal cells - In the enterocyte endoplasmic reticulum, glycerol is converted into a-glycerolphosphate (a-GP). - In the enterocyte, a-GP, FA, MAG, and DAG are reformed to TAG. - The reformed lipids, along with apo-B48, form a chylomicron that leaves the enterocyte, travels through the lymph, and ends in blood circulation. Other apolipoproteins are transferred to the chylomicrons from other lipoprotein complexes. ## Plasma Lipoproteins - **Free Cholesterol:** Amphipathic phospholipids and free cholesterol form a monolayer surrounding nonpolar "neutral" lipids. - **Phospholipid:** Surrounds the core of the lipoprotein. - **Cholesteryl Ester:** Found surrounding the core of the lipoprotein. - **Triacylglycerol:** Found surrounding the core of lipoprotein. - **Core of mainly nonpolar lipids:** Found inside of the lipoprotein and consists mostly of triacylglycerol. - **Monolayer of mainly polar lipids:** Found outside of the entire lipoprotein and consists of mainly phospholipids and free cholesterol. ## Lipoprotein Classes - **Chylomicron:** Composed of: - 82% Triacylglycerol - 7% Phospholipid - 2% Cholesterol - 9% Protein - **Very-Low-Density Lipoprotein (VLDL):** Composed of: - 52% Triacylglycerol - 18% Cholesterol - 22% Phospholipid - 8% Protein - **Intermediate-Density Lipoprotein (IDL):** Composed of: - 31% Triacylglycerol - 22% Cholesterol - 29% Phospholipid - 18% Protein - **Low-Density Lipoprotein (LDL):** Composed of: - 9% Triacylglycerol - 23% Cholesterol - 47% Phospholipid - 21% Protein - **High-Density Lipoprotein (HDL):** Composed of: - 3% Triacylglycerol - 28% Cholesterol - 19% Phospholipid - 50% Protein ## Exogenous Lipid Transport - Chylomicrons are assembled in the small intestine, where they obtain apoB-48 and apoA-1 - Apolipoproteins E and C-II are transferred to the chylomicron. - Chylomicrons transport the triacylglycerols to tissues, including adipose and muscle. - Lipids are transferred to tissues, where they are broken down by lipoprotein lipase. - The chylomicron remnant is formed; they attach to the liver binding site containing hepatic lipase, and the fatty acids, cholesterol, and cholesteryl esters are transferred to the liver. ## Lipoprotein Metabolism in Adipocytes - Glucose is metabolized to make acetyl-CoA, which can be converted to fatty acids. - Lipoprotein lipase acts on TAG in chylomicrons, which causes free fatty acids (FFA) and MAG to enter the adipocyte. - Lipoprotein lipase acts on VLDL so FFA and MAG enter the cell. - Pathways favor energy storage as TAG. Insulin stimulates lipogenesis by promoting entry of glucose into the cell and by inhibiting the hormone-sensitive lipase that hydrolyzes the stored TAG to FFA and glycerol. ## Lipoprotein Metabolism in the Liver - Dietary nutrients enter the liver through the portal vein. - Glucose can be converted to glycogen or enter glycolysis. - Amino acids enter the amino acid pool, and some are metabolized to produce pyruvate and oxaloacetate. - Serum FFA, bound to albumin, enter the fatty pool and are TAG. - The liver packages the chylomicron remnant, and returns the fatty acids, cholesterol, and cholesteryl esters to the liver. - TAG, C, and PL, are packaged with apolipoproteins and enter the circulation as VLDL. - VLDL deliver triacylglycerols to muscle and adipose tissue. ## Endogenous Lipid Transport - Nascent VLDL is made in the Golgi apparatus of the liver. - The newly made VLDL obtains apo-C and apo-E from HDL - The fatty acids from triacylglycerols (TAG) in VLDL are hydrolyzed by lipoprotein lipase found mainly in muscle and adipose tissue. - As the TAG is removed from VLDL, the particle becomes smaller and becomes an IDL. - Further loss of TAG and it becomes a LDL. - LDL are taken up by LDL receptors found in the liver and non-hepatic tissue. ## Sequential Steps in Endocytosis of LDL - LDL particle with apoB attaches to the LDL receptor. - Endocytosis of LDL particle and receptor. - LDL particle fuses with lysosome. - LDL receptors return to the membrane surface. - Proteins of LDL particle are hydrolyzed to amino acids. - Free cholesterol is released from LDL particle. - HMG-CoA reductase is involved in cholesterol synthesis. When excess cholesterol is present, synthesis of cholesterol and LDL receptors are inhibited. - Cholesterol transferred to Golgi, esterified with ACAT, and stored in the cell. ## Reverse Cholesterol Transport - Lipid-free apoA-1 is secreted by the liver and intestine. - Apo A-1 acquires PL and C from interaction with ABCA1, resulting in nascent HDL particles. - Nascent HDL acquire additional PL and C via ABCA1 and additional C via SR-B1 in peripheral tissues. - The enzyme LCAT, carried on HDL particles, esterifies C to CE that migrate to the particle core. - The now spherical mature HDL continue to acquire PL and C via ABCG1 and C via SR-B1 in peripheral tissues. - LCAT continues to esterify C to CE, forming larger HDL. - Some CE are transferred to VLDL and LDL, mediated by CETP. - Liver SR-B1 binds HDL. CE may be selectively removed, or the HDL particle may be internalized and degraded. ## Apolipoprotein Table | Apolipoprotein | Lipoprotein(s) | Molecular mass (Da) | Additional Remarks | |---|---|---|---| | apo A-1 | HDL, chylomicrons | 28,000 | Activator of lecithin: cholesterol acyltransferase (LCAT); ligand for HDL receptor | | apo A-2 | HDL, chylomicrons | 17,000 | Structure is two identical monomers joined by a disulfide bridge; function unknown | | apo A-4 | Secreted with chylomicrons, but transfers to HDL | 46,000 | Associated with the formation of triacylglycerol-rich lipoproteins; function unknown | | apo B-100 | LDL, VLDL, IDL | 550,000 | Synthesized in liver; ligand for LDL receptor | | apo B-48 | Chylomicrons, chylomicron remnants | 260,000 | Synthesized in intestine | | apo C-1 | VLDL, HDL, chylomicrons | 7,600 | Possible activator of LCAT | | apo C-2 | VLDL, HDL, chylomicrons | 8,916 | Activator of extrahepatic lipoprotein lipase | | apo C-3 | VLDL, HDL, chylomicrons | 8,750 | Several polymorphic forms depending on content of sialic acids | | apo D | Subfraction of HDL | 20,000 | Possible antioxidant | | apo E | VLDL, HDL, chylomicrons, chylomicron remnants | 34,000 | Ligand for chylomicron remnant receptor |