Aghdas, Keith, Kevin, Laura, and Maria The Digestion of Fats Aghdas, Keith, Kevin, Laura, and Maria

Outline Lipid and Cholesterol Background Digestion in Mouth, Esophagus, and Stomach Digestion in the Small Intestine Absorption in the Small Intestine The Fate of Dietary and Endogenous Fats in Circulation Fat Utilization and Storage by Body’s cells Health Concerns

Lipid Background Information Major source of energy in the body Along with carbohydrates, fats account for most of the calories consumed in food Primarily consist of hydrocarbon chains and rings Nonpolar, organic molecules; insoluble in polar solvents (i.e. water); hydrophobic Types: Triglycerides (Fats & Oils) Steroids (cholesterol: steroid hormone parent molecule) Ketone bodies (derivatives of free fatty acids) Phospholipids

Triglyceride (Fats & Oils) 1 glycerol molecule (3-carbon) + 3 fatty acids Hydroxyl group (glycerol) & carboxyl group (fatty acid)

Fatty Acids Short chain fatty acids Less than 8 carbons Broken off from triglycerides; do not require bile acids Short-chain fatty acids  portal vein  liver (without chylomicrons) Long chain fatty acids 16+ carbons Digestion starts in small intestine; require bile acids & lipases Absorption and Transport

Cholesterol Structure and Functions Four fused rings as the core, shared by all steroids. Membrane component Precursor to Bile acids Vitamin D Steroid hormones

CHOLESTEROL: Synthesis The liver manufactures most of the cholesterol in our bodies The intestine and all cells contribute a small amount Overall, the body produces about 2.0 g per day Serum cholesterol levels are homeostatically controlled

Digestion in the Mouth Little to no digestion in the mouth for adults The salivary glands of newborn babies produce lipase

Cholesterol Synthesis Pathway Cholesterol is created from acetyl-CoA The rate-limiting and irreversible step in the pathway is the conversion of HMG-CoA to Mevalonate HMG-CoA reducatase is the enzyme responsible for this step Drugs targeting high plasma cholesterol targets this step

Digestion in the Esophagus/Stomach No digestion in the esophagus Only the peristaltic movement of the food bolus Little to no digestion in stomach The stomach’s acidic environment produces chyme

Digestion in the Small Intestine This is where digestion of fats begins Fat absorption primarily occurs in the duodenum and jejunum Key Players Bile Pancreatic Lipase Pancreatic Colipase

Bile Produced by the liver and stored in the gallbladder Cholecytokinin (CCK) is released in SI due when fat in chyme reaches duodenum; Stimulates gallbladder to release bile Consists of bile salts, bilirubin, phospholipids, cholesterol and inorganic ions Bile salts: bile acids such as cholic acid or chenodeoxycholic acid conjugated with glycine or taurine Bile salts are mainly responsible for the emulsification of the fats by creating the micelles The micelles increase the exposed surface area of the fats for lipase to do its work Define bile salts (pg 631) CCK

Pancreatic Lipase/Colipase CCK also stimulates the release of Lipase from the pancreatic duct into the duodenum. As bile is emulsifying fat droplets, lipase is chemically digesting the fat The hydrolysis reaction results in 2 Free fatty acid chains and a monoglyceride These products enter the micelles and now they are called mixed micelles Colipase coats emulsifaction droplets and anchors lipase to these droplets Monoglycerides and free fatty acid

Absorption in Small Intestine The Mixed Micelle is absorbed by the intestinal epithelium which has increased surface area due to villi and microvilli The free fatty acids and monoglcyerides resynthesize to become triglycerides within the epithelium cell The fats combine with cholesterol, phospholipids and proteins to form a chylomicron The chylomicron is then transported into the central lacteals just deep to the epitheliumlymphatic systemvenous flow via thoracic duct and into circulation

Dietary Fats in Circulation Once the chylomicron enters the blood, an apolilpoprotein (ApoE) complexes with it Now the chylomicron-ApoE complex binds onto the ApoE receptors on the plasma membrane of capillary endothelial cells in muscle and adipose tissue Lipoprotein lipase digests the triglycerides The remnant chylomicron containing cholesterol is eventually taken up by the liver The liver can use free fatty acids, monoglycerides, and cholesterol received from HDL’s for energy purposes

The Role of the Liver Produces endogenous triglycerides and cholesterol and combines them with ApoE to form VLDLs (very-low density lipoproteins) VLDLs deliver triglycerides to the body’s cells and subsequently become low-density lipoproteins (LDL’s) LDL’s now deliver cholesterol to the body’s cells Excess cholesterol and phospholipids bond and return to the liver as cholesterol esters via high-density lipoproteins (HDLs) Define VLDL, LDL, HDL???? Explain cholesterol esters

Fat Utilization by the Body’s Cells The body’s tissues store fats in adipose cells and utilize them after the depletion of the glucose supply Beta-oxidation: enzymes remove two carbon acetic acid from the acid end of fatty acid chain resulting in 1 acetyl-CoA (12 ATP for one cycle through Kreb’s + 1NADH + 1FADH2) Example: 16 carbon long fatty acid 96 ATP + 3 ATP + 2 ATP 101 ATP!!!!

Lipogenesis: Fat Synthesis/Storage The formation of fat when blood glucose levels are high Occurs in Adipose tissue and in the liver 1. Glucose  3-phosphoglyceraldehyde  glycerol 2. Acetyl-CoA  fatty acid chains

Lipogenesis (From Amino Acids) Proteins can be converted to fats by deamination Isoleucine, Leucine, and tryptophan can be converted to Acetyl-CoA which can be transformed into fatty acid chains Alanine, Cysteine, Glycine, Serine, and Trytophan can be converted to pyruvate which can be indirectly converted into glycerol FATTY ACID

Health Concerns Atherosclorosis /High Cholesterol/Statins Saturated fats Unsaturated fats Polyunsaturated fats Omega-3 fats Omega-6 fats Ketone Bodies

Lipoproteins, Cholesterol, & Atherosclerosis Atherosclerosis: plaques (cholesterol, lipids, smooth muscle cells) protrude into artery lumen & reduce blood flow Risk: high blood cholesterol (diet) LDLs (carrying cholesterol to organs & blood vessels) contribute to development of atherosclerosis HDLs (carrying excess cholesterol from organs & blood vessels to liver) help protect against development of atherosclerosis High LDL cholesterol treatment: Statins: inhibit enzyme HMG-coenzyme A reductase (catalyze cholesterol synthesis); reduce liver’s ability to produce cholesterol; decreased intracellular cholesterol promotes production of LDL receptors (increase in liver uptake of LDL cholesterol)

Degree of Saturation of Fats Saturated: A fatty acid with a carbon chain containing all the hydrogens that it can hold -elevates LDL cholesterol Monounsaturated:A fatty acid with a carbon chain that contains one double bond -can lower LDL cholesterol levels Polyunsaturated:A fatty acid that contains two or more double bonds -can help lower blood cholesterol levels

Ketone Bodies In times of fasting or when immediate energy is needed, the liver can convert free fatty acids into acetyl-CoA then into ketone bodies (Ketogenesis) Large amounts of ketone bodies are released into the blood to supply the body’s cells However, in a low-carbohydrate diet or diabetes mellitus, the rapid triglyceride breakdown can lead to Ketosis Then if the excess ketone bodies lowers the blood pH then its called Ketoacidosis Ketosiselevated levels of ketone bodies in the blood

Omega-3 and Omega-6 Fatty Acids Polyunsaturated, essential fatty acids Omega-3 acid (linolenic acid) Omega-6 fatty acid (alpha-linolenic acid): increased ratio of omega-6 to omega-3 is associated with heart disease and increased allergies and asthma incidence.

Summary Ingestion of lipids in the form of triglycerides and cholesterol Fats are propelled into the esophagus and then into the stomach Bile salts and pancreatic lipase breakdown fats in the S. I. Dietary and Endogenous Fats in Circulation Fat metabolism Health concerns Fats is placed into the mouth… salivary glands and stomach (of newborn) produce lipase (enzyme).. Little to no fat digestion occurs From the mouth, it goes down to the esophagus to the stomach where HCl is present and makes it possible to produce chyme Chyme arrives in the duodenum of S.I. where bile and pancreatic juice breakdown fats. Then, it is absorbed into the intestinal epithelial cells. Formed into triglycerides, phospholipids again… then triglyceride, phospolipid and cholesterol mix with protein to form vesicles called chylomicrons.. Transport of blood… dietary fat circuation/endogenous circulation Fat can be used as stored energy when there’s no more glucose… used for ATP synthesis………..// excess fat is stored in fat depots (hips, abdomen, breasts) Health concerns

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