Lipid Digestion and Absorption

1. Lipid Digestion in the Mouth and Stomach:

• Lipases in the mouth and stomach can only hydrolyze triglycerides (TGs) with short and medium chain fatty acids (? 12C).

2. Role of Cholecystokinin (CCK):

• CCK is a hormone that stimulates the contraction of the gallbladder, releasing bile into the small intestine. At the same time, CCK also stimulates the pancreas to secrete digestive enzymes, including pancreatic lipase.

3. Function of Bile Salts:

• Bile salts play a crucial role in the emulsification of lipids, forming micelles. Micelles increase the surface area of contact between pancreatic lipase and TGs, making the hydrolysis process more efficient.

4. Function of Pancreatic Lipase:

• Pancreatic lipase is the main enzyme involved in lipid digestion in the small intestine. Pancreatic lipase hydrolyzes fatty acids at positions C1 and C3 of the TG molecule, releasing free fatty acids and monoglyceride. In addition, pancreatic lipase also secretes esterases that function to cut fatty acids from cholesteryl esters and phospholipids.

• Pancreatic lipase is most effective at pH = 6.

5. Fatty Acid Absorption:

• Approximately 95% of bile salts are reabsorbed in the ileum and reused.

• Fatty acids, after being separated from TGs, are absorbed directly through the wall of the small intestine.

• Fatty acids travel to the liver via veins and combine with albumin for transport in the blood.

6. Lipid Digestion and Absorption Process:

• The lipid digestion and absorption process includes the following steps:

1. Emulsification of lipids by bile salts.

2. Hydrolysis of TGs by pancreatic lipase.

3. Diffusion of hydrolysis products into the small intestinal mucosa.

4. Formation of chylomicrons.

5. Chylomicrons enter the lymphatic system and then the bloodstream.

6. Hydrolysis of TGs by lipoprotein lipase (LP lipase).

7. Fatty acids enter tissue cells.

8. Fatty acid oxidation to generate energy in tissues.

7. Chylomicron:

• Chylomicrons are lipoproteins with the largest diameter, the least dense, and the highest content of TGs among lipoproteins.

• Chylomicrons are formed by small intestinal cells, packaging TGs, proteins, and phospholipids together. Chylomicrons are delivered to the lymphatic system and then enter the subclavian vein.

• Chylomicrons contain apoprotein B48, apoE, and apoCII.

8. Lipoprotein (LP):

• LPs are spherical particles with a structure consisting of two layers: a shell and a core.

• Shell: Composed of single phospholipids alternating with free cholesterol.

• Core: Contains TGs and cholesteryl esters.

• There are two types of apoproteins:

• Apoproteins located outside the shell: ApoAI, ApoE, ApoCII.

• Apoproteins bound to the core: ApoB100, ApoB48.

• Apoproteins play a role in:

• Facilitating the transport of LP particles.

• Recognizing LP for liver cells and tissues.

• Activating enzymes required for TG hydrolysis and esterification.

9. Remnant Chylomicron:

• Remnant chylomicrons contain cholesterol, apoE, apoB48, and mainly TGs.

• Remnant chylomicrons travel through the bloodstream to the liver.

• Liver surface receptors recognize apoE.

• Inside the liver cells, remnant chylomicrons release cholesterol and are completely degraded.

10. VLDL (Very Low Density Lipoprotein):

• Excess fatty acids and glucids are re-synthesized into TGs and packaged as VLDL.

• VLDL contains apoB100, apoCI, apoCII, apoCIII, apoE, cholesterol, and cholesteryl esters.

• VLDL is synthesized in liver cells and travels through the blood to muscle and adipose tissue.

11. LDL (Low Density Lipoprotein):

• LDL can be converted from VLDL.

• LDL contains a large amount of cholesterol and cholesteryl esters.

• The main apoprotein of LDL is apoB100.

• LDL travels to extrahepatic tissues with membrane receptors that recognize apoB100.

• LDL is called “bad cholesterol” because it is associated with cholesterol deposition in the walls of blood vessels, leading to atherosclerosis.

12. HDL (High Density Lipoprotein):

• HDL is synthesized in liver and small intestinal cells.

• HDL is rich in protein, low in cholesterol, and does not contain cholesteryl esters.

• HDL contains apoAI, apoCI, apoCII, other apoproteins, and LCAT.

• LCAT on the surface of newly synthesized HDL functions to convert lecithin and cholesterol of CM and VLDL into cholesteryl esters contained in HDL.

• Newly synthesized HDL becomes mature HDL after receiving cholesteryl esters.

• Mature HDL travels through the blood back to the liver.

• In the liver, cholesteryl esters are used to synthesize biological compounds such as bile salts, steroid hormones.

• HDL is taken up or only transfers lipids to the liver through selective membrane transport mechanisms.

• HDL is called “good cholesterol” because it functions to collect excess cholesterol from tissues and deliver it to the liver for excretion.

13. Atherosclerosis:

• Atherosclerosis is associated with increased LDL and decreased HDL.

14. Fatty Acid Oxidation:

• Fatty acid oxidation depends on the saturation, length, and chain structure of fatty acids.

• Fatty acid ?-oxidation is divided into groups:

• Long chain saturated fatty acids with even number of Cs.

• Long chain saturated fatty acids with odd number of Cs.

• Unsaturated fatty acids.

• Very long chain fatty acids and branched chain fatty acids.

• The main fatty acids oxidized to generate energy are long chain fatty acids released from TG reserves in adipose tissue.

• Fatty acid oxidizing enzymes are mainly concentrated in mitochondria.

15. ?-oxidation Process:

• ?-oxidation includes three steps:

1. Activate fatty acids into the active form as acyl coA.

2. Acyl coA is transported from the cytoplasm into the mitochondria.

3. Oxidation of acyl coA in the mitochondria.

• Fatty acid oxidation mainly occurs in liver cells.

16. Fatty Acid Transport:

• Fatty acids are transported in the blood and into cells by binding to albumin.

• Activation of fatty acids into acyl coA requires 2 ATPs.

• Acyl coA is transported from the cytoplasm into the mitochondria by the carnitine enzyme and CAT (CPT).

17. CAT (CPT):

• CAT has 2 isozymes:

• CAT I (CPT I) in the outer mitochondrial membrane.

• CAT II (CPT II) in the inner mitochondrial membrane.

• CAT I catalyzes carnitine esterification with acyl coA to form acyl carnitine and releases HSCoA.

• CAT II transfers the acyl group in acyl carnitine to coA in the mitochondria to form acyl coA and releases carnitine.

18. ?-oxidation of acyl coA Stage:

• ?-oxidation of acyl coA includes 3 stages:

1. ?-oxidation of acyl coA to acetyl coA.

2. Acetyl coA enters the citric acid cycle to form electrons and CO2.

3. Electrons from the above 2 stages enter the cellular respiratory chain to form ATP.

• Each oxidation cuts 2 Cs in the form of acetyl coA.

• Acyl coA undergoes 4 chemical reactions until it is completely cut into acetyl coA.

19. Energy from ?-oxidation:

• The energy generated during the oxidation of palmitic acid 16C is 106 ATPs.

20. Regulation of ?-oxidation:

• ?-oxidation activity is regulated by:

• Cellular energy requirements.

• CoA concentration in mitochondria.

• CPT I activity.

21. Regulation of ACC:

• ACC activity is regulated by:

• AMP concentration.

• Insulin and glucagon hormone pair concentration.