Lipids Pt 2.docx

Dietary Lipids Digestion of lipids (for monogastric) begins in the mouth and ends in the small intestines. Digestion of lipids in the stomach is limited but is catalyzed by the following digestive enzymes: Lingual lipase (produced by glands at the back of the tongue) Gastric lipase (secreted by gast...

Dietary Lipids Digestion of lipids (for monogastric) begins in the mouth and ends in the small intestines. Digestion of lipids in the stomach is limited but is catalyzed by the following digestive enzymes: Lingual lipase (produced by glands at the back of the tongue) Gastric lipase (secreted by gastric mucosa cells) Both lingual and gastric lipase are acid stable (pH 4-6)- AKA: acid lipases. Meaning, that digestion can continue in the stomach with both enzymes despite the lowered pH going from the mouth to the stomach. Acid lipases hydrolyze triglycerides (TAG). Specifically, the TAGs containing SCFA (short chain length fatty acids) or MCFA (medium chain length fatty acids)- fatty acids that have less than 12 carbons in the chain. SCFA are very commonly found within milk fat. Therefore, making acid lipases very important in lipid digestion for infants. The pancreas is the main organ for lipase synthesis and secretion. Lipid Digestion: General Info Lipid digestion is different than the process of carbohydrate digestion because lipids are hydrophobic and carbohydrates are hydrophilic, meaning that lipids will not dissolve in water like carbohydrates can. Lipids require detergent action to emulsify (dissolve) lipids so that they can be digested by hydrolytic enzymes such as lipases. Lipid assimilation can be divided into 4 phases: Emulsification Hydrolysis Micelle formation Absorption Lipid Digestion: Emulsification Emulsification starts in the stomach and moves to the duodenum of the small intestines. Emulsification aims to increase the surface area of hydrophobic lipid droplets. This is essential for lipase function so the enzymes can bind at the interface of the droplet/aqueous solution. Emulsification is completed by these 2 complementary mechanisms: Mechanical mixing due to peristalsis Peristalsis is the involuntary constriction and relaxation of smooth muscles of the intestines or another canal, creating wave like motions that push contents of the canal forward. Using detergent properties of conjugated bile salts (within the duodenum) Bile salts are made of bile acids. Bile salts are synthesized by the liver and stored in the gall bladder. Bile salts are amphipathic derivatives of cholesterol. Bile salts consist of a steroid ring with a amino acid side chain (glycine or taurine). Ball salts emulsify fat droplets. Bile is a mixture of bile salts, phospholipids, and free cholesterol. Lipid Digestion: Hydrolysis (with Pancreatic Enzymes) TAG TAGs are too large to be absorbed in the small intestines and therefore, must be hydrolyzed by pancreatic lipase and co-lipase. The end products for absorption (after hydrolysis) are 1 MAG (monoglyceride) and 2 FFA (free fatty acids). CE (cholesteryl ester) Dietary cholesterol and CE are mostly from animal sources. CE gets hydrolyzed by cholesteryl esterase. This enzymes activity is increased bile salts. The end products for absorption (after hydrolysis) are cholesterol and FFA. Phospholipids (PL) Pancreatic juice is rich in phospholipases. This enzymes activity is increased bile salts. The end products for absorption (after hydrolysis) are lysophospholipid and FAF. Lipid Digestion: Mixed Micelles Step 1: The end products of the hydrolytic products combine with bile salts to form mixed micelles. Micelles are aggregations of surfactant amphipathic lipid molecules (bile salts + digested lipids) dispersed in a liquid solution, forming a colloidal suspension. Step 2: The soluble micelles transport the lipids from the gut lumen to the mucosal layer. Step 3: The lipids are transported into close contact with absorptive surface of the enterocytes. Lipid Digestion: Absorption (by the enterocytes) Step 1: The products from the lipid hydrolysis stage of digestion include: FFA, free cholesterol, and MAG. Note: SCFA and MCFA were immediately brought to the enterocyte membrane (without the use of micelles) and bypassed the hydrolysis stage. Step 2: The FFA, free cholesterol, and MAG combined with bile salts and lipid soluble vitamins (A, D, E, K) to form mixed micelles. Step 3: The mixed micelles were transported to the brush border membrane of the enterocytes. The mixed micelle is absorbed here, except for the bile salt composition. The brush border membrane of the enterocytes is the primary site of lipid absorption. Due to majority of fats being absorbed within the enterocytes, there is typically very little fat found within fecal matter. Step 4: The bile salts reabsorbed in the ileum and are brought into the hepatic portal system where the bile salts are recycled by the liver. Lipid Digestion: Re-esterification (in the Enterocytes) Step 1: After being absorbed by the enterocytes, lipids move to the smooth ER (sER) for re-esterification. Re-esterification involves: MAG being converted to TAG. Lysophospholipid being converted to phospholipid. Cholesterol + Fatty Acids being converted to cholesteryl ester. Re-esterification is essentially when the products of the hydrolysis step of digestion get converted back into their original forms that they were prior to the hydrolysis taking place. Step 2: The end products of re-esterification are transported to the Golgi apparatus for the maturation of the chylomicron. A chylomicron is a lipoprotein with a spherical structure that is used for lipid transport. The core of the chylomicron is made of TAG and CE, while the surface is made of phospholipids and cholesterol. This assembly is essential for the molecule’s stability. Lipid: Secretion from the Enterocytes SCFA and MCFA are not re-esterified. Instead, they are immediately released into the hepatic portal system where they attach to albumin and are transported to the liver. Step 1: Re-esterified lipids (from sER), proteins (from rER), and cholesterol (from sER) are packaged in the Golgi apparatus into structures called “chylomicron”. Step 2: Chylomicrons are released via exocytosis from the enterocytes into the lymphatic vessel (lacteals). Step 3: Chylomicron then travels into the thoracic duct. Step 4: Chylomicron then travels to the left subclavian vein. Step 5: Chylomicron enters the blood. Control of Lipid Digestion Pancreatic secretion of lipase (hydrolytic enzyme of lipids) is controlled by the hormones cholecystokinin (CCK) and secretin. The small intestines is divided into the duodenum, jejunum, and ileum. CCK CCK is a peptide hormone that is produced by the I-cells of the duodenum. CCK is produced in response to lipids and proteins entering the small intestines. CCK will stimulate: The secretion of bile from the gall bladder The secretion of digestive enzymes from the pancreas Decreased gastric motility Secretin Secretin is a peptide hormone produced by S-cells by the duodenum. Secretin is produced in response to low pH of chyme in the stomach. Secretin will stimulate: Bicarbonate (HCO3) secretion from the pancreas to neutralize (raise) the pH to what is optimal for pancreatic enzymes. Use of Dietary Lipids by Tissue TAG will be degraded into FFA and glycerol. This will take place in the capillaries of peripheral tissue (primarily in skeletal muscle and adipose tissue, also in heart, lungs, kidney, liver). The lipoprotein lipase (LPL) enzyme located in the endothelial cells of capillaries is what is doing the degradation of the TAG into the FFA and glycerol. FFA can take any of the following paths: Remain in the blood (bound to a plasma protein) Enter muscle cells or organ cells to produce energy Enter adipocytes to store the FFA as TAG Glycerol will enter the liver to synthesis glycerol-3-phosphate, which can then be used for either glycolysis or gluconeogenesis. Chylomicron remnants will do endocytosis into the liver where they will be hydrolyzed into their remainder components. These remainder components will then be recycled. Case Study A patient (a 3yr old German shepherd) presented for weight loss despite having a good appetite. The patient has developed to urge to eat its own feces. The feces is now soft, grey in color, and has a claylike consistency. Upon exam, the patient was noted to have a dull, uneven, greasy coat. Diagnostics showed steatorrhea (fat in the feces). Fat maldigestion and absorption is a common sign for pancreatic exocrine insufficiency- which could be the cause of steatorrhea. Because there is a insufficiency of pancreatic lipase, fats can’t be hydrolyzed to fatty acids for absorption and thus pass unabsorbed through the gut. Other causes of steatorrhea include: Bile salt deficiency (possibly due to bile duct obstruction or liver disease) Defective chylomicron synthesis (inside the enterocytes) Lymphatic obstruction (so the chylomicron won’t reach the blood plasma) Lipid malabsorption and maldigestion can result in vitamin deficiency. This is because sub-optimal levels of pancreatic enzymes would impair the solubilization and absorption of fat-soluble vitamins A, E, K, D. In severe cases, patients can develop coagulopathy from vitamin K deficiency.