Digestion, Absorption, Secretion, and Utilization of Dietary Lipids PDF

# DIGESTION, ABSORPTION, SECRETION, AND UTILIZATION OF DIETARY LIPIDS - An adult ingests about 60 to 150 g of lipids per day, of which more than 90% is normally triacylglycerol (TAG). - The remainder of the dietary lipids consists primarily of cholesterol, cholesteryl esters, phospholipids, and un...

# DIGESTION, ABSORPTION, SECRETION, AND UTILIZATION OF DIETARY LIPIDS - An adult ingests about 60 to 150 g of lipids per day, of which more than 90% is normally triacylglycerol (TAG). - The remainder of the dietary lipids consists primarily of cholesterol, cholesteryl esters, phospholipids, and unesterified ("free") fatty acids. - in the stomach, acid stable lingual and gastric lipases digest TAG, particularly those containing fatty acids of short- or medium-chain length (< 12 carbons, such as are found in milk fat), - Emulsification of dietary lipids occurs by the bile salts, and mechanical mixing due to peristalsis. - The dietary triacylglycerol, cholesteryl esters, and phospholipids are enzymatically degraded ("digested") by pancreatic enzymes, whose secretion is hormonally controlled - Triacylglycerol degradation: pancreatic lipase preferentially removes the fatty acids at carbons 1 and 3. The primary products of hydrolysis are thus a mixture of 2-monoacylglycerol and free fatty acids - Cholesteryl ester degradation: pancreatic cholesterol esterase, produces cholesterol plus free fatty acids - Phospholipid degradation: Pancreatic Phospholipase A2 removes one fatty acid from carbon 2 of a phospholipid, leaving a lysophospholipid. The remaining fatty acid at carbon 1 can be removed by lysophospholipase, leaving a glycerylphosphoryl base ## Control of lipid digestion: 1. **Cholecystokinin:** Cells in the mucosa of the jejunum and lower duodenum produce a small peptide hormone, cholecystokinin (CCK) in response to the presence of lipids and partially digested proteins - CCK acts on the gallbladder (causing it to contract and release bile), and on the exocrine cells of the pancreas (causing them to release digestive enzymes). 2. **Secretin:** in response to the low PH of the chyme entering the intestine. Secretin causes the pancreas and the liver to release a watery solution rich in bicarbonate that helps neutralize the PH of the intestinal contents, bringing them to the appropriate pH for digestive activity by pancreatic enzymes. ## Absorption of lipids by intestinal mucosal cells (enterocytes) - Free fatty acids, free cholesterol, and 2-monoacylglycerols are the primary products of dietary lipid degradation in the jejunum. These, together with bile salts, form mixed micelles - Short- and medium-chain length fatty acids do not require the assistance of mixed micelles for absorption by the intestinal mucosa. - The mixture of lipids absorbed by the enterocytes migrates to the endoplasmic reticulum where biosynthesis of complex lipids takes place. ## Lipid Transport & Storage - Fat absorbed from the diet and lipids synthesized by the liver and adipose tissue must be transported between the various tissues and organs for utilization and storage. Since lipids are insoluble in water, so it is transported by formation of water miscible lipoproteins. - Plasma lipids consist of triacylglycerols (16%), phospholipids (30%), cholesterol (14%), and cholesteryl esters (36%) and a much smaller fraction of unesterified long-chain fatty acids (4%). This latter fraction, the free fatty acids (FFA), is metabolically the most active of the plasma lipids. - Because fat is less dense than water, the density of a lipoprotein decreases as the proportion of lipid to protein increases (Table 3). In addition to FFA, four major groups of lipoproteins have been identified. These are: 1. **Chylomicrons (CM)**, derived from intestinal absorption of triacylglycerol and other lipids 2. **Very low density lipoproteins (VLDL, or pre-ẞ-lipoproteins)**, derived from the liver for the export of triacylglycerol 3. **Low-density lipoproteins (LDL, or ẞ-lipoproteins)**, representing a final stage in the catabolism of VLDL 4. **High-density lipoproteins (HDL, or a-lipoproteins)**, involved in VLDL and chylomicron metabolism and also in cholesterol transport. ## Table: 3 Composition of the lipoproteins in plasma of humans. | Lipoprotein | Source | Main Lipid Components | Apolipoprotein | | -------------- | --------- | -------------------------------- | --------------- | | CM | Intestine | Triacylglycerol | A, B-48, C, E | | Chylomicron | CM | Triacylglycerol, phospholipids, cholesterol | B-48, E | | remnants | | | | | VLDL | Liver | Triacylglycerol | B-100, C, E | | IDL | VLDL | Triacylglycerol, cholesterol | B-100, E | | LDL | VLDL | Cholesterol | B-100 | | HDL | Liver, intestine, VLDL, chylomicrons | phospholipids, Cholesterol | A, C, E | | Albumin/free | Adipose tissue | Free fatty acids | | | fatty acids | | | | ## Table: 4 function of apoproteins | Apoprotein | Function | | ---------- | -------------------------------------------------- | | A-1 | Activates LCAT, Structural in HDL | | B-100 | Receptor binding, Structural in LDL & VLDL | | B-48 | Structural in chylomicrons | | C-II | Activator of LPL | | C-III | Inhibits LPL and clearance of CM and VLDL remnant particles | | E | Binding to LDL and remnant receptors | ## Lipoprotein Metabolism ### Chylomicrons - CM are formed from dietary fat (principally triglycerides, but also cholesterol) in enterocytes; they enter the lymphatics and reach the systemic circulation via the thoracic duct. - CM are the major transport form of exogenous (dietary) fat. - Triglycerides are removed from CM by the action of the enzyme lipoprotein lipase (LPL) - LPL located on the luminal surface of the capillary endothelium of adipose tissue, skeletal and cardiac muscle and lactating breast - The result that free fatty acids are delivered to these tissues to be used either as energy substrates or, after re-esterification to triglyceride, for energy storage. LPL is activated by apo C-II. - Apo A and apo B-48 are synthesized in the gut and are present in newly formed CM, apo C-II and apo E are transferred to CM from HDL. - As triglycerides are removed from CM by the action of LPL, these become smaller; cholesterol, phospholipids, apo A and apo C-II are released from the surface of the particles and taken up by HDL. - Esterified cholesterol is transferred to the CM remnants from HDL, in exchange for triglyceride, by cholesteryl ester transfer protein (CETP). - The CM remnants are cleared via the recognition of apo E by hepatic remnant receptors - Although their major function is the transport of dietary triglyceride, CM also transport dietary cholesterol and fat-soluble vitamins to the liver. Under normal circumstances - CM cannot be detected in plasma in the fasting state (>12 h after a meal). ### VLDL - VLDL are formed from triglycerides synthesized in the liver either de novo or by re-esterification of free fatty acids. VLDL also contain some cholesterol, apo B, apo C and apo E; the apo E and some of the apo C is transferred from circulating HDL. - Triglycerides is removed by the action of LPL. - As the VLDL particles become smaller, phospholipids, free cholesterol and apolipoproteins are released from their surfaces and taken up by HDL, thus converting the VLDL to denser particles, IDL. - Cholesterol that has been transferred to HDL is esterified and the cholesteryl ester is transferred back to IDL by CETP in exchange for triglyceride. - More triglycerides are removed by hepatic triglyceride lipase, and IDL are thereby converted to LDL, composed mainly of cholesteryl esters, apo B-100 and phospholipid. - Some IDL are taken up by the liver via LDL receptors. These receptors, also known as B, E receptors, are capable of binding apo B-100 and apo E (but not apo B-48). - Under normal circumstances, there are very few IDL in the circulation because of their rapid removal or conversion to LDL. ### HDL - HDL are synthesized primarily in the liver and, to a lesser extent, in small intestinal cells, as a precursor ('nascent HDL') comprising phospholipid, cholesterol, apo E and apo A. - Nascent HDL is disc shaped; in the circulation, it acquires apo C and apo A from other lipoproteins and from extra hepatic tissues, and in doing so assumes a spherical conformation. - The free cholesterol is esterified by the enzyme LCAT, which activated by apo A-I. - This increases the density of the HDL particles, and converts HDL3 to HDL2. - Cholesteryl esters are transferred from HDL2 to remnant particles in exchange for triglycerides, this process being mediated by CETP. - Cholesteryl esters are taken up by the liver in CM remnants and IDL and excreted in bile, partly after metabolism to bile acids. - Thus HDL has two important functions: 1. it is a source of apoproteins for CM and VLDL, 2. it mediates reverse cholesterol transport, taking up cholesterol from senescent cells and other lipoproteins and transferring it to remnant particles, which are taken up by the liver. Cholesterol is excreted by the liver in bile, both as free and esterified cholesterol and after metabolism to bile acids