Lipid Digestion* Flashcards
Be able to list 3 advantages of storing energy as fat (TG).
- Carbons in triglycerides have a lower oxidation state than carbons in carbohydrate or protein. More than twice the energy per (dry) weight!
- TG are stored in an anhydrous state, whereas carbo- hydrates have twice their dry weight as bound water.
- Fats don’t participate in the cell’s osmotic balance (no bound water), so they can be stored to a large fraction of the cell volume.
For these reasons, Triglycerides are the major storage form of metabolic energy.
carbohydrate 4 kcal/g
protein 4 kcal/g
alcohol 7 kcal/g
fat 9 kcal/g
Understand how TG is digested and how the products of TG digestion are absorbed by intestinal cells (including roles of pancreatic lipase, colipase, bile salts).
- Bile acts as a detergent.
- Bile is needed for lipid dispersion (emulsification) — not just of TG, but of other lipids, including fat- soluble vitamins (ADKE).
- Bile contains:
- bile acids
- phosphatidyl choline
- cholesterol
Digestion of FA involves the hydrolysis of ester bonds in TG, in reactions catalyzed by TG- specific esterases called lipases. Long-chain TG (LCT) are insoluble in water and must be emulsified before digestion can occur. Chewing and stomach contractions produce finely dispersed lipid droplets. Some digestion (~20 %) occurs in the stomach through the action of lingual and gastric lipases, enzymes with an acid pH optimum. Further emulsification in the small intestine is aided by the presence of bile acids, which function as digestive detergents.
Pancreatic lipase digests TG in lipid droplets:
• Enzyme activation requires formation of a complex with colipase & a droplet of emulsified lipid, stabilizing the ‘open’ conformation & allowing access to substrate while shielding against bile salts that inactivate the enzyme.
• The enzyme lipase is an esterase, cleaving preferentially at the 1 & 3 positions of TG, releasing 2-MAG and FA.
Most of the TG is hydrolyzed by pancreatic lipase in the small intestine (duodenum and proximal jejunum). Digestion occurs at water-lipid interfaces, which are greatly increased in extent by emulsification. Lipase access to lipid substrates requires another protein, colipase (which is secreted as an inactive precursor by the pancreas and activated in the duodenum through the action of trypsin). Pancreatic lipase is an esterase (with a pH optimum around 7) that catalyzes the partial hydrolysis of TG containing long-chain fatty acids, with a preference for the 1 and 3 positions. The main products are thus 2-monoacylglycerol (2-MAG) and NEFA.
Products of lipid digestion (2-MAG + NEFA) are absorbed into cells of intestinal mucosa.
• Products are first incorporated into mixed micelles that cross the stationary aqueous boundary layer at the intestinal wall.
• Then free fatty acids, monoacylglycerol, and glycerol all diffuse or are transported by carrier proteins into the intestinal mucosa cells.
The next step after digestion is absorption of the digestion products. This process requires bile, which is produced in the liver and secreted into the duodenum (proximal part of small intestine). Bile components are: bile acids (also called bile salts), phosphatidylcholine, and cholesterol.
• Bile acids form mixed micelles with the nonpolar digestion products (mainly 2-MAG and NEFA), permitting their translocation across the stationary aqueous boundary layer at the intestinal wall. In mixed micelles the glycerol backbones are oriented toward the aqueous phase.
• Actual uptake of digestion products by intestinal cells was long thought to be an entirely passive process (occurring through diffusion), but recent evidence points to a predominant contribution from carrier-mediated transport. A member of the Fatty Acid Transport Protein family, FATP5, is the major FA transporter in enterocytes. A member of the aquaporin family, AQP3, mediates glycerol transport.
• Bile salts thus have a dual role: functioning in both digestion and absorption. Bile salts remain in the lumen and do not enter the fat-absorbing enterocytes; bile acids are absorbed later on farther down the intestine (enterohepatic recirculation).
Understand how TG is resynthesized in intestinal mucosa cell and exported in lipoprotein particles called chylomicrons.
In the intestinal cell, TG is resynthesized from 2-MAG and then packaged into lipoprotein particles called chylomicrons that are exported into the lymph:
- Intestinal mucosal cells (also called enterocytes) resynthesize TG from the absorbed LCFAs and 2-monoacylglycerols. Once inside the cell, LCFAs are not free but bound to intestinal FA- binding protein as they move about.
- Acyl-CoA synthetase (thiokinase) catalyzes formation of acyl-CoA derivatives of LCFA. Acyltransferases (transacylases) then catalyze the transfer of 2 LCFA moieties to 2-MAG
- The TG produced in intestinal cells must be transported through the lymph and blood to tissues that use TG as a source of fuel.
- For transport through the lymph and blood, water-insoluble TG must be packaged into a type of lipoprotein particle, called chylomicrons. All lipoprotein particles (as the name implies!) contain proteins and lipids. Polar groups of lipids and proteins tend to be at the surface, nonpolar groups tend to be buried in the interior.
- Apo-B48 is the principal protein component of nascent chylomicrons as they are produced in the intestinal mucosa
Understand general structural features of lipoproteins.
All lipoprotein particles (as the name implies!) contain proteins and lipids. Polar groups of lipids and proteins tend to be at the surface, nonpolar groups tend to be buried in the interior.
Understand transport of TG in lipoproteins and release of FA from lipoproteins by lipoprotein lipase so that FA can be used directly as a fuel (by many but not all body tissues) or stored for future use as fuel (mainly in adipocytes).
FA are subsequently released from lipoproteins (chylomicrons) by the action of lipoprotein lipase located in the capillary endothelial walls of various tissues (especially muscle and adipose tissue). Lipoprotein lipase is similar in action to pancreatic lipase, but the specificity is different. In this case, cleavage occurs at all 3 ester bonds, so the products are glycerol and NEFA.
- Chylomicrons are cleared rapidly from the blood (i.e., delipidated) by the action of lipoprotein lipase; the half-life of a chylomicron particle is about 10 min.
- Serum obtained a few hours after a fatty meal is often milky, reflecting the high concentration of chylomicrons.
- Insulin promotes the release of lipoprotein lipase from adipocytes and muscle. This released lipoprotein lipase becomes bound to the capillary walls of adipose and muscle tissue, adding to the amount of enzyme available to act on lipoprotein particles. The result is increased hydrolysis, increased uptake of NEFA — to be used as fuel (muscle) or to be stored (adipocytes)
Note: Brain CANNOT use free FA as fuel (blood-brain barrier prevents transport).
Be familiar with FA: short-, medium- and long-chain
• Most human FA have an even number of carbons.
- short-chain (SCFA): 2 to 4 carbons
- medium-chain (MCFA): 6 to 10 (or 12) carbons -long-chain (LCFA): 12 (or 14) to 26 carbons. Long-chain FA are the most abundant.
Be familiar with FA: saturated vs. unsaturated
no double bonds (termed saturated FA) or one or more double bonds (termed unsaturated FA)
In polyunsaturated FA, double bonds are usually neither adjacent (-HC=C=CH-) nor conjugated (-HC=CH-HC=CH-) since this would make the structure too easily oxidized. They are almost always separated by a methylene group
(-CH=CH-CH2*-CH=CH-).
Be familiar with FA: stereochemistry and spacing of double bonds
Naturally occurring FA double bonds have a cis configuration, which introduces a rigid 30° bend that interferes with the packing of hydrocarbon side chains. Thus, a TG with side chains containing double bonds will have a lower melting temperature than a TG with only saturated FA side chains.
Be familiar with FA: structures of 8 of the commonest long-chain FA
See pg. 187 for the 8 LCFA–PURPLE
State the 3 main causes of steatorrhea (excessively fatty stools):
Not an objective*
- Failure of bile production or blockage of bile flow
- Exocrine pancreas dysfunction or obstruction of pancreatic duct
- Failure of uptake into intestinal mucosal cells (enterocytes)
Dietary fat is not the only source of FA used as fuel; NEFA may also be released from fat stored in adipocytes. Also, de novo synthesis of FA occurs in the liver and adipose cells. Liver cells convert FA to glycerol esters (TG) and then package the TG into VLDL particles that are released into the plasma. Lipoprotein lipase releases FA from VLDL, just as it does with chylomicrons. Therefore, Lipoprotein lipase has 2 functions
