The Digestion of Fats

Aghdas, Keith, Kevin, Laura, and Maria

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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 Concerns2

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

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Triglyceride (Fats & Oils)

• 1 glycerol molecule (3-carbon) + 3 fatty acids

• Hydroxyl group (glycerol) & carboxyl group (fatty acid)

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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

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Cholesterol Structure and Functions

• Four fused rings as the core, shared by all steroids.

• Membrane component

• Precursor to– Bile acids

– Vitamin D

– Steroid hormones

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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

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Digestion in the Mouth

• Little to no digestion in the mouth for adults

• The salivary glands of newborn babies produce lipase

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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

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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

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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

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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

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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

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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 epitheliumlymphatic systemvenous flow via thoracic duct and into circulation

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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

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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)

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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!!!!

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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

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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

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FATTY ACID

Health Concerns

• Atherosclorosis /High Cholesterol/Statins

• Saturated fats• Unsaturated fats• Polyunsaturated fats• Omega-3 fats• Omega-6 fats• Ketone Bodies

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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)

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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

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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

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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.

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Summary

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THE END

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