L33: Digestion of Dietary Lipids Flashcards
Minimal digestion of lipids in the stomach by which two acid lipases? What are their properties?
Lingual lipase - produced by glands at the back of the tongue
- Gastric lipase - produced by the gastric mucosa Properties:
- Acid stable, pH optimum 4-6
- Digest TAGs with short chain fatty acids (<C12’s)
- Neonates depend primarily on milk fat for calories. Human breast milk also contains an acid stable lipase
- Also important for patients with pancreatic insufficiency such as cystic fibrosis
colipase
•A small protein secreted by the pancreas in an inactive form, procolipase
•Activated in the intestinal lumen by trypsin
•Structure
–nonpolar domain (tail): embedded in emulsion droplet
–polar domain (head): binds to the C-terminal; anchors & activates lipase enzymes
A required cofactor for optimum lipase activity. Pancreatic lipase which hydrolyzes >80% of dietary fat requires colipase for its activity. Overcomes inhibitory effect of bile salts
triacylglycerol degredation
- Major component (~ 90%) of dietary fat and too large to be taken up by the mucosal cell of the intestinal villi
- Pancreatic lipase is an esterase which removes FAs from C#1 and C#3 of TAG with high catalytic efficiency
- Pancreatic lipase is present in high concentrations in pancreatic secretions
- Pancreatic lipase binds to colipase which anchors it to the emulsified fat droplet
- Deficiency causes significant malabsorption of dietary fat
- Clinical Note: Orlistat (an antiobesity drug) inhibits pancreatic lipase
Phospholipid degredation
- Pancreatic juices contain enzymes for phospholipid digestion
- Phospholipase A2 is produced as a proenzyme and activated by trypsin
- Requires bile salts for optimum activity
- One FA from C#2 from the phospholipid is removed
- FA attached to C#1 of lysophosphatidylcholine is next removed by lysophospholipasen
- Remaining glycerol with phosphate + other head groups (choline etc) is excreted in the feces, further degraded or absorbed
- Snake venom contains phospholipase A2 and causes the rapid lysis of erythrocyte membranes
Cholesteyl Ester degredation
- Dietary cholesterol is a mixture of free cholesterol (85 to 90%) and cholesteryl ester (10 to 15%)
- Humans cannot metabolize the ring structure of cholesterol (gut bacteria can to some extent)
- Cholesteryl esterase produces cholesterol + free fatty acids
- Requires bile salts for optimum activity
Cholescytokinen (CCK)
Produced by cells of lower deodunum and jejunum
• Produced in response to presence of lipids and partially digested proteins entering the upper small intestine
• Induces bile secretion from gall bladder
• Induces pancreatic lipase secretion
• Decreases gastric motility
Secretin
- Causes pancreas and liver to release bicarbonates
* Bicarbonates neutralize stomach acid and restore pH for lipase action
What do mixed micelles contain?
The end products of lipid digestion: free fatty acids, monoacyl glycerol, free cholesterol, along with bile salts and fat soluble vitamins in the diet (A,D,E and K) come together to form this mixed micelle in the upper small intestine.
Absorption of digested lipids
•Micelles are disk shaped water soluble particles, having hydrophillic groups on the surface and hydrophobic groups on the inside.
•Micelle components are taken up by the small intestine brush border cells
•Cholesterol is poorly absorbed. Bile salts are absorbed in the ileum
NOTE: Short and medium chain fatty acids DO NOT need to form micelles
-bile salts are absorbed in the ilieum (NOT by the mucosal cell) and recycled
-cholesterol in general is poorly absorbed by the enterocytes
Re-synthesis of lipids in the erterocyte and chylomicron formation
•Absorbed fats are reassembled into TAG, Cholesteryl ester (CE) & phospholipids in the ER of intestinal cells
•Packaged into Chylomicrons
•Apolipoprotein B-48 & phospholipids on the
surface
•TAG, fat-soluble vitamins and CE on the inside
•Chylomicrons are carriers of dietary fats & Vits in the lymph and blood
Chylomicron Secretion and transport
- Chylomicrons (CMs) are released into the interstitial fluid by exocytosis
- CMs enters the lymphatic system at the lacteal by diffusion
- Flow of lymphatic fluid carries CMs into the blood at the thoracic duct
- CMs can be seen in the blood 1 to 2 hours after a meal
- CMs can also deliver fat to adipose and muscle tissue
Assimilation of Digested Lipids
Digested lipids are delivered via circulation to adipose and skeletal muscle in the form of chylomicrons. Lipoprotein lipase, located in the
capillary beds of adipose and muscle tissue catalyzes the hydrolysis of TAG in CM to release all the three FA chains attached to glycerol. These
released fatty acids are used as fuel in muscle or stored in adipose tissue. Glycerol goes to the liver where it is utilized for glycolysis or gluconeogenesis. Lipoprotein lipase removes most (~90%) of the TG in the CM resulting in the formation of a chylomicronremnant. Chylomicron remnant contains fat-soluble vitamins, cholesterol, and any undegraded TAG. Chylomicron remnants are sent to the liver.
What is Steatorrhea and what are some causes?
excess lipid in the feces
1) insufficient bile salt release by the gallbladder (cholestasis). Results in poor emulsification of dieatary lipids and low accessibility of the dieteary lipids to digestive enzymes
2) insufficient production of pancreatic enzymes (eg during cystic fibrosis)
3) poor absorption of digested fats due to defective intestinal mucosal cells
Patients with steatorrhea exhibit a deficiency of essential fatty acids and vitamins. The ability of short- and medium-chain length fatty acids to be taken up by enterocytes without the aid of mixed micelles has made them important in dietary therapy for individuals with digestion and malabsorption disorders.
Cystic Fibrosis & pancreatic insufficiency
caused by mutations to the CFTR gene (chloride channel). It causes chronic lung infections with progressive pulmonary disease. Defective CFTR results in decreased secretion of chloride and increased reabsorption of sodium and water. In the pancreas, the decreased hydration results in thickened secretions of the pancreatic juice Pancreatic lipases do not reach the intestine. Treatment includes replacement of these enzymes and supplementation with fat-soluble vitamins.
Lipoprotein lipase deficiency
a rare autosomal disorder caused by a deficiency of the lipase enzyme located in the capillary beds of adipose and muscle tissue. This deficiency results in poor degradation of TAG & release of
FAs from chylomicrons. This results in chylomicronemia which is characterized by a buildup of chylomicrons in the blood. Lipase enzyme deficiency can also occur by a deficiency of its coenzyme.
