Lipids Water insoluble Substances Soluble in organic solvents (acetone, benzene) Important in human nutrition Very concentrated form of energy, important biomolecules Types of Lipids Simple Lipids: †Fatty Acids, †Triglycerides Compound Lipids: †Phospholipids †Cholesterol †Eicosanoids †Lipoproteins (VLDL, LDL, HDL, Chylomicrons) †Fat Soluble Vitamins (A,D,E,K)

Fat Cells cellwww.umm.edu/.../graphics/images/en/19267.jpg www.blueprintsolution.com/.../fat_cells.jpg

Mortality http://www.cartoonstock.com/lowres/mba0054l.jpg http://hcna.radcliffe-oxford.com/images/obese%201-2.jpg

Fatty Acids Structure

Fatty Acids Fatty Acids - straight hydrocarbon chain with a terminal Carboxyl (COOH) †Saturated- no double bond †Unsaturated- contains > one double bonds ¶ Monounsaturated- one double bond ¶ Polyunsaturated- 2 or more double bonds †Essential FA- body cannot produce, must come from diet Formula .... CH3(CH2)nCOOH †Carbon # varies (in nature normally even #) i.e.: 16C, 18C †Normally 4-24 † Most abundant 16-18-20

Always a 3 Carbons difference between double bonds Linoleic and Linolenic are essential Fatty Acids

Fatty acids: different health effect different kinds: food fats Canola oil, olive oil, safflower oil, fish oil butter, beef tallow, lard, palm oil, coconut oil saturated Unsaturated monounsaturated, polyunsaturated fatty acids Omega 3 - , Omega 6 - fatty acids essential fatty acids, trans- fatty acids

Good Sources Monounsaturated fat: (plant: good source) canola oil, olive oil Polyunsaturated fat: (plant: good source) vegetable oil, sunflower oil, safflower oil Omega 3 fat - plant, fish Tropical oil: palm oil, coconut oil: (Plant): highly saturated: limit the intake Limit saturated fat: animal source butter, beef fat, lard

Omega 6-, Omega 3- Fatty Acids Normally, numbering of Carbon starts at carboxyl carbon In Omega system, numbering starts from the opposite end (CH3-, omega) Linoleic acid : Omega 6 Fatty Acid CH3-C-C-C-C-C=C-C-C=C-C-C-C-C-C-C-C-COOH (First double bond is located on the 6th Carbon, this is an Omega 6 Fatty Acid) Linolenic acid : Omega 3 Fatty Acid CH3-C-C=C-C-C=C-C-C=C-C-C-C-C-C-C-C-COOH (First double bond on the 3 Carbon) Both are highly unsaturated

Omega-3 and Omega-6 Fatty Acids Compared

Omega 3 FA † Decreases incidence of cardiovascular disease • Health Benefits † Decreases incidence of cardiovascular disease † Decreases blood cholesterol levels † Decreases blood clotting by decreasing platelet aggregation AMA Recommendation: Eat fish meal: 2-3 times /week (10 oz) Good for brain development and function, normal vision, heart, immune system, memory Fish oil supplements: recommended with consultation with a doctor

n-3 fatty Acids Come in the Diet † Linolenic Acid- from plants † Eicosapentaenoic Acid (EPA)- 20:5D † Docosahexaenoic Acid (DHA)- 22:6D Italicized---> highly unsaturated and originate in fish oils Important for making 3 Types of Important Biomolecules † Prostaglandins † Leukotrienes † Thromboxanes

Hydrogenation Physical Property of fats Saturated- animal foods (solid, room temp) Mono, poly unsaturated fat - plant foods (liquid) Adding “H” at the double bonds changes Liquid vegetable oil to solid: hydrogenation ( un-saturation  saturation): Trans fatty acids (Trans fat) Hydrogenation generates trans fatty acids, Trans fats - fried foods

Hydrogenation 21

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FDA - Trans Fat – Heart Disease Food and Drug Administration in the United States as of (January 2006) requires food manufacturers to list trans fat on nutrition facts labels. Read the ingredient label and look for shortening, hydrogenated or partially hydrogenated oil. The higher up on the list, the more trans fat is present in the food. A 1994 Harvard University study found more than twice the risk of heart attacks among those who ate partially hydrogenated oils, which are high in trans fat, compared to those who consumed little trans fat. Trans fatty acids are responsible for nearly 30,000 premature deaths per year in the U.S.

“Potential” Dangers Consuming trans fats: Increase the levels of bad cholesterol and promote heart disease and circulatory disorders. Depress the body's immune system. Interfere with pregnancy and are related to low birth weight babies, and poor quality breast milk. Worsen diabetes, hypertension and obesity by increasing insulin resistance. Displace healthy fats, for example, the omega-3 fatty acids in fish oils, preventing them from performing their normal function. Disturb liver function.

Hydrogenation- addition of H+ at the double bond of liquid oil --> solid fat (increases the melting point) example: shortening or margarine Emulsification- breakdown (dispersion) of large fat molecules into small fat particles (globules) physiological emulsifiers- bile, lecithin examples: homogenization of milk Rancidity and Oxidation (spoilage) of fat @ the double bond forms a peroxide: bad taste and smell Antioxidant (Vit E) added to oil to prevent spoilage

Triglyceride (Triacylglycerol) • Typically known as FAT • Most abundant (in nature and in body) form of lipid • Neutral Fat   Triacylglycerol monoacyglycerol= monoglyceride diacylglycerol = diglyceride Triglyceride= glycerol + 3 Fatty Acids

Figure 6.5 Monoacylglycerol structure and stereospecific numbering. Fig. 6-5b, p. 132

Figure 6.4 Chemical structure of a monoacylglycerol (left) and a diacylglycerol (right). Fig. 6-4, p. 132

Triacylglycerol Structure

Structure of Triacylglycerol

Phospholipids (Glycerophosphatides) • Structural Lipid • Polar lipid • 1 Glycerol + 2 Fatty Acid chains + 1 Phosphate Group (+ another group to classify the P-lipid) • Main lipid found in plasma membrane to give structure, and outside of lipoproteins  

Phospholipids

Phospholipids

Phospholipids

Cholesterol in Plasma Membrane

Ch 10: Plasma Membrane: Lipid Bilayer Phospholipids: have both hydrophobic and hydrophilic region Forming bilayer: Allow: hydrophobic groups inside and hydrophilic groups outside of the membrane Major: phosphatidyl choline (Lecithin) Lecithin In every single cell Synthesized in the body From foods: liver, egg yolk, soybean Emulsifier

Phospholipids are Part of Lipoproteins Transport vehicles for lipid in blood Lipids are hidden inside lipoproteins Chylomicron: made in intestine VLDL: made in intestine, liver LDL: made from VLDL in blood HDL: made in intestine, liver

Cells Functional unit of life None typical: all different Fig. 10.1: Human cell: Liver cell Plasma membrane Outer boundary Keeps cell composition constant Selective permeability

Animal Cell Membrane

Transport Mechanism

Na K ATPase

Na Glucose CoTransport

Cholesterol Structure

CH 32 Digestion and Transport of Dietary Lipids Dietary Fat is made of † Triglyceride (must abundant , 95% of total dietary fat) † Phospholipids † Cholesterol † Fat Soluble Vitamins Lingual Lipase in mouth and gastric lipase hydrolyze mostly milk fat (short and medium chain fatty acids (carbon # fewer than 12) (important during infancy) Major digestion Stomach contents enter Small Intestine--> release of cholecystokinin (CCK): gut hormone --> release of bile & pancreatic lipase , colipase, bicarbonate (neutralize acidic stomach contents) (hormone secretin stimulate bicarbonate release) bile breaks fat into small particles pancreatic lipase works on small fat particles TG --> free fa + 2-monoglyceride + some glycerol

Triacylglycerols Digestion

Bile Bile recirculation Emulsifier: Break fat into small pieces ‘Bile’: made in Liver stored in Gallbladder acts in Small Intestine reabsorbed in Ileum (Entero Hepatic Cycle) (intestine < --- >liver) Bile recirculation Total bile pool: 2.5 – 5.0 g > 90% is reabsorbed, ~ 0.5 g is lost in feces/day Pool of bile recycle twice/ meal Soluble fibers bind to bile  excreted Drugs bind to bile promote excretion of bile in feces  to lower blood cholesterol

Recycling of Bile Salts

Bile Salt

Action of Pancreatic Lipase

Cholesterol ester and phospholipids digestion

Fat Digestion

Fat Absorption Depending on the length of the fatty acids chain † Short and medium chain fatty acids are absorbed --> portal vein --> liver † Long chain FA, 2- monoacylglycerols, glycerol, bile, Vitamins, cholesterol and lysophospholipids aggregate to form micelle (lump of these particles)  micelles move to microville  all of these particles are absorbed into intestinal cells, bile is not absorbed.

Resynthesis of triacylglycerol in intestinal epithelial cells

Triacylglycerol (TG) Absorption In the enterocyte, a “new” triaclyglycerol is formed from fat digested fragments absorbed from micelles--- “New” Triglyceride + Phospholipid + Fat Soluble Vitamins + Cholesterol: packaged, and apoprotein is added - --> formation of lipoprotein This lipoprotein is called Chylomicron (CM) Chylomicron is too large to pass directly into the blood stream. Instead. It is taken through lymph. CM is released into the bloodstream at thoracic Duct.

Made from exogenous (dietary) fat Chylomicron • Chylomicron-->high in TG, low in cholesterol, protein and phospholipids Made from exogenous (dietary) fat • Transported through lymph--> then, blood stream • In blood, some TG in CM is digested by lipoprotein lipase in the capillary of adipose cells to Fatty acids and glycerol. Fatty Acids are take up by the adipose cells : what is left is called Chylomicron Remnants --> return to Liver

Lipoprotein Structure

Chylomicron

Chylomicron

4 Types of Lipoproteins • Chylomicron made in intestine • VLDL liver, intestine • LDL circulation • HDL liver, intestine † if it has more fat than protein, then it’s a lower density lipoprotein like VLDL † if more protein than fat, then it’s a higher density lipoprotein like HDL 

Fate of Chylomicron

Transfer of ApoE and ApoCII from HDL to chylomicron Apo E is recognized by membrane receptor on liver cell: Apo E bearing particles enter liver by endocytosis  fused with lysosomes  digested  contents are reused ApoCII: activator of LPL: enzyme on capillary endothelial cells on muscle and adipose cells: digest triacylglycerol of chylomicron and VLDL: fatty acids are taken in

Liver and Adipose in Lipid Metabolism Exogenous free fatty acids of shorter chain: absorbed into portal vein  liver Chylomicron remnant : enters the liver from blood circulation  in the liver cell, chylomicron remnant (c.r.) is fused with lysosome  all components of c. r. such as cholesterol, amino acids, phospholipids come out to cytosol. Absorbed dietary TG from c.r. and newly synthesized TG (from glucose metabolism) are packaged into VLDL VLDL comes out to blood some TG is taken up by the body cell (mostly adipose cells)  what is left is IDL or LDL

Liver’s Importance in Lipid Metabolism Site of bile formation: made from cholesterol Synthesis of lipoprotein VLDL VLDL is made from endogenously made fat (fat made in liver) † VLDL is rich in TG and cholesterol † VLDL leaves the liver--> blood --> some TG is taken up by cell  leaving it as IDL, then eventually made to LDL (rich in cholesterol- 60-70% total content) HDL is synthesized in peripheral tissue