Unit 3 Study Guide (Vazhaikkurichi Rajendran) PDF

Lecture 23: Electron Transport and Oxidative Phosphorylation Electron (e-) Transport Chain (ETC) - 4 Complexes of ETC present in the inner membrane of mitochondria Complex 1: catalyzes the e- transfer from NADH coenzymes Q (UQ) Complex 2: catalyzes the e- transfer from FADH2 to coenzyme Q...

Lecture 23: Electron Transport and Oxidative Phosphorylation Electron (e-) Transport Chain (ETC) - 4 Complexes of ETC present in the inner membrane of mitochondria Complex 1: catalyzes the e- transfer from NADH coenzymes Q (UQ) Complex 2: catalyzes the e- transfer from FADH2 to coenzyme Q (UQ) Complex 3: transfers the e- from reduced UQ (UQH2) to cytochrome c (Cyt. c) Complex 4: catalyzes 4 e- to O2 to form H2O Electron Transfer by Complex-1 -Complex-1 (NADH Dehydrogenase Complex): catalyzes the e- transfer from NADH to enzyme Q (UQ) - During the e- transfer from NADH to UQ by complex-1, 4 H+ are pumped out from the matrix into the intermembrane space UQ: lipid-soluble e- carrier shuttles the e- between ETC complexes along the inner mitochondrial membrane Electron Movement by Complex-2 - Complex-2 (Succinate Dehydrogenase Complex): catalyzes the transfer e- from FADH2 to UQ - During the e- transfer from FADH2 to UQ, H+ is not pumped out of matric into the intermembrane space UQ can also get e- from acyl-CoA and glycerol-3-phosphate dehydrogenases Electron Movement by Complex-3 - Complex 3 (Cytochrome bc 1 Complex): transfers e- from reduced UQ (UQH2) to cytochrome c (Cyt c) Takes one e- at a time from UQH2 and transfers to Cyt c. - During e- transfer from UQH2 to Cyt c by complex-3, 4 H+ are pumped out from the matrix and in the intermembrane space Cyt c carries only 1 e- Cyt c is a water-soluble mobile e- carrier of the outer face of the intermembrane Electron Movement in Complex-4 - Complex-4 (Cytochrome Reductase): transfers 4 e- from 4 Cyt c to O2 to form H2O - During e- transfer from Cyt c to O2 by complex-4, 4 H+ are pumped out from matrix into intermembrane ATP can act as an allosteric inhibitor of cytochrome oxidase by binding to complex-4 and Cyt c Energy Relationships in ETC - NADH oxidation results in a substantial energy release This energy is used to pump H+ from matrix into the intermembrane space, which establishes H+ gradient to generate ATP 2.5 molecules of ATP are synthesized per NADH 1.5 molecules of ATP are synthesized per FADH2 Oxidative Phosphorylation and Chemiosmotic Theory - Oxidative Phosphorylation: process that conserves the energy of the ETC by phosphorylation of ADP → ATP As the e- pass through the ETC, H+ are pumped out of the matrix into the intermembrane space, generating H+ motive force - Chemiosmotic Coupling Theory: H+ moves back from intermembrane space into matrix across the membrane through ATP synthase driving ATP formation Explains how oxidative phosphorylation links the ETC and ATP synthesis Evidence for the Chemiosmotic Theory - pH drops in a weakly buffered mitochondria suspension when actively respiring - Disruption of inner membrane stops respiration - Uncouplers: (Dinitrophenol) picks up protons from one side and release on the other side to collapse the H+ gradient - Ionophores: (Gramicidin A) form a channel, allow for passage of proton to disrupt the proton gradient ATP Synthase Structure - ATP synthase consists of two rotors linked by a strong flexible stator - Two major components: F1 unit (ATP synthase) and F0 unit (transmembrane channel) F1 unit has 5 subunits: 3𝛼, 3𝛽, 𝛶, δ, ε F0 unit has 3 subunits: a, 2b, and 12c - F0 unit converts the proton motive force into rotational force of the central shaft (𝛶 and ε subunits) that, in turn, drives ATP synthase - 1 molecule of ATP synthesis requires translocation of 3 protons through the ATP synthase Cross section of ATP Synthase and Shaft Locations - ATP synthase is composed of 3𝛼 and 3𝛽 subunits All 3 𝛼 subunits (𝛼1, 𝛼 2, 𝛼 3) are the same size and shape All 3 𝛽 subunits (𝛽1, 𝛽2, 𝛽3) are the same size and shape. ^ 𝛽-subunits consist of: ADP binding site, Pi binding site Conformational changes of 𝛽-subunit - 𝛽 subunits of the ATP synthase goes through conformational changes: loose (L), tight (T) and open (O) When 𝛶-shaft touches 𝛽1: “L” conformation- ADP and Pi bind to their respective site When neither 𝛶 or ε has touches 𝛽1: 𝛽1 has “T” confirmation - ADP and Pi join to form ATP When 𝛽1 is in contact with ε: 𝛽1 has “O” confirmation - ATP released to matrix ATP, ADP and Pi Transport - ATP synthase synthesizes ATP delivered into matrix ATP exits the matrix though ADP-ATP translocator (ADP-ATP exchange) ADP gets into matrix through ADP-ATP translocator (ADP-ATP exchange) -The required Pi is transported as H2PO4 though phosphate translocase H2PO4 co-transport with H+ Regulation of Oxidative Regulation - High ADP (respiratory control) and Pi level in matrix activate oxidative phosphorylation - High ATP level in matrix inhibits the oxidative phosphorylation  The matrix ATP and ADP level is controlled by the ADP-ATP translocator The matrix H2PO4- level is controlled by phosphate translocase (H2PO4- /H+ symporter) Mechanisms to move cytoplasmic NADH into Matrix (Glycerol-Phosphate Shuttle) - NADH reduces Dihydroxyacetone phosphate (DHAP) to glycerol-3-phosphate Glycerol-3-Phosphate diffuses through the mitochondrial outer membrane and reduces FAD to FADH2. ^ Complex-2 of ETC transfer electron from FADH2 to UQH2 Mechanisms to move cytoplasmic NADH into Matrix (Malate-Aspartate Shuttle) - Cytoplasmic NADH reduces oxaloacetate → malate Malate is transported to the matrix - Malate is re-oxidizes to produce NADH Lecture 24: Reactive Oxygen Species and Antioxidants Reactive Oxygen Species - All living processes take place with a RedOx environment - Oxygen usage comes with the danger of forming: Reactive Oxygen Species (ROS) Reactive Nitrogen Species (RNS) - ROS and RNS: oxygen containing molecules with uneven # of electrons (e- ← “Free Radicals”) Normal ROS level: help fight pathogens Normal RNS level: damages fat, protein, and nucleic acids Antioxidants and Oxidative Stress - Antioxidants: can donate e- to neutralize ROS without compromising their stability and mitigate oxidative damage - Oxidative Stress: an imbalance between ROS and antioxidants Under certain conditions, antioxidant mechanisms are overwhelmed → Oxidative Stress Oxidative damage has been linked to hundreds of human diseases Cell Function and Oxidative Stress - Many proteins of metabolic and signaling pathways are involved in redox rxns - Activation and inactivation of proteins (e.g. enzymes) are altered during redox rxns - Oxidation of sulfhydryl (SH) group in protein: Sulfenic (SOH) acid Sulfinic (R-SO2H) acid Sulfonic (R-SO3H) acid ^change in functional properties of these molecules - Redox change occurs during cellular processes: Cytoplasm of cells that enter cell division become more reduced Cytoplasm of differentiates cells are more oxidized - Intracellular Compartments are different redox conditions: Nucleus/mitochondria are more reduced (GSH/GSSH is High) ER is more oxidized (GSH/GSSH is low) Oxidative Phosphorylation and ROS Formation - Reactive Oxygen Species (ROS)/Free Radicals: O2- : Superoxide Radical H2O2 : Hydrogen Peroxide OH : Hydroxyl Radical - Electron (e-) leaks out of ETC due to aging/over exertion - E- could possibly exit ETC while the e- are transferred by complex-1 and complex-3 E- reacts with O2 and creates superoxide radical (O2-) Additional e- reacts with O2- → Hydrogen Peroxide (H2O2) H2O2 reacts with ferrous iron (Fe2+) → OH Reactive Nitrogen Species (RNS)/Free Radicals - Reactive Nitrogen Species: NO- : Nitric Oxide (good) NO2 : Nitrogen dioxide ONOO- : Peroxynitritrite - Superoxide radical (O2-) reacts with NO- to form peroxynitrite  O2- + NO- → ONOO- - “ONOO-” has nitrating and oxidizing functions. It damages protein and nucleic acid. - “NO-” is an important signaling molecule. It regulates blood pressure, inhibits blood clotting, and destruction of foreign cells by macrophages Radical Chain Reaction 1.) Lipid peroxidation rxns begins after the extraction of hydrogen atom ⏺ from an unsaturated fatty acid (LH-L) 2.) Lipid radical (L ) rxts with O2 to form a peroxyl radical (L+ O2 → L-O-O) 3.) The radical chain rxn begins when the peroxyl radical extracts a hydrogen atom from another fatty acid molecule (L-O-O+L’H → L-O-OH+L’) 4.) In the presence of transition metal, such as Fe2+ initiates further radical formation (L-O-O-H+Fe2+ → LO+OH- + Fe3+) 5.) One of the most serious consequences of lipid peroxidation is the formation of 𝛼,𝛽-unsaturated aldehyde, which involves a radical cleavage rxn. 6.) The chain continues as the free radical product, then rxts with nearby molecule 7.) Reactive carbonyl products are also products of this process Respiratory Burst - ROS also generated during Respiratory Burst: Macrophages and neutrophils actively make large quantities of ROS to destroy pathogens (microorganisms) - Macrophages/Neutrophils phagocytose the pathogen and form phagosomes - The NADPH-oxidase present on the phagolysosome membranes convert O2 to O2- - O2- rxts with several other molecules to generate OH, -OCL, ONOO-, and NO2 radicals The free radicals destroy the bacteria ROS/RNS kills pathogens - Phagocytosis: bacterium → receptor → phagosome + lysosome → phagolysosomes →Exocytosis -debri Antioxidants - To protect against oxidative stress, living organisms have developed several antioxidants (defense mechanisms) Enzyme Systems: -Superoxide Dismutase -Catalase - Glutathione-centered system  - Thioredoxin-centered system Molecule Systems: - 𝛼-Tocopherol (Vitamin-E) - 𝛽-carotene (Vitamin A) - Ascorbic Acid (Vitamin C) Enzyme Systems Antioxidants Hydrogen peroxide (H2O2) generation and degradation - Superoxide Dismutase (SOD): catalyzes formation of H2O2 and O2 from superoxide radical 2O-2 + 2H+ →(SOD)→ H2O2 + O2 - Catalase degrades the H2O2 into H2O and O2. Catalase present in peroxisome 2 H2O2 → Catalase → 2 H2O + O2 Glutathione-centered System - Glutathione (GSH)-centered system consists of 2 enzymes: glutathione peroxidase and glutathione reductase: Glutathione Peroxidase: Uses GSH to reduce H2O2 to form water and transforms organic peroxides to alcohols. During this process GSH is oxidized to GSSG. 2 GSH + R-O-OH → (GPx) → G-S-S-G + R-OH + H2O Glutathione reductase: uses NADPH to reduce GSSG to GSH G-S-S-G + NADPH + H+ → (Glutathione Reductase) → 2 GSH + NAD+ Thioredoxin-Centered System - Thioredoxin-centered system: Consists of 2 enzymes: Perodiredoxin (PRX) and Thioredoxin Reductase TRX: proteins that act as a antioxidant -The oxidized TRXs (TRS-S2) are reduced by Thioredexin reductase enzyme that utilizes NADPH PRX: uses thiol-containing peptides like TRX to detoxify organic peroxides Chemicals/Molecules Antioxidants 𝛼-Tocopherol, 𝛽-carotene, Ascorbic Acid - 𝛼-Tocopherol (Vitamin-E): potent, lipid-soluble radical scavenger - protects membranes from lipid peroxyl radicals - 𝛽-carotene (Vitamin A): a carotenoid, is a precursor of vitamin A (retinol): a potent, lipid-soluble radical scavenger in membranes - Ascorbic Acid (Vitamin C): efficient antioxidant, present as ascorbate, scavenger variety of water soluble ROS Ascorbic Acid - Scavenges ROS and aqueous compartment of cells and extracellular fluids - Reacts with peroxyl radicals and protects membranes by preventing lipid peroxidation - enhances the antioxidant activity of vitamin E by regenerating Alpha-tocopherol - Protects membrane through two mechanisms: Scavenging a variety of ROS and aqueous environments enhancing the activity of alpha-tocopherol Lecture 25: Lipid Structure and Classification 1 Lipids and Lipid Classification - Lipids: Substances from living things that can be dissolved in nonpolar solvents Can be used for energy storage, membrane structure, chemical signals, vitamins, or pigments - Lipid Classification: 1.) Fatty Acids 2.) Triglycerides 3.) Wax Esters 4.) Phospholipids 5.) Sphingolipids 6.) Isoprenoids 1.) Fatty Acids - Fatty acids are: monocarboxylic acids, contain hydrocarbon chains of variable lengths (12-26 or more carbons) Most of the naturally occurring fatty acids have an even number of carbons in an unbranched chain - Saturated Fatty Acids: Fatty acids that contain only single carbon-carbon bonds - Unsaturated Fatty Acids: Fatty acids that contain one or more double bonds Numbering Systems of Fatty Acids - Numbering of fatty acids starts from Carboxyl C - The 𝛼-carbon is adjacent to the carboxyl group - The terminal methyl carbon is denoted as the omega (𝜔) carbon Fatty acids are important for triglycerides and phospholipids Unsaturated Fatty Acids - Unsaturated Fatty Acids: Fatty acids that contain one or more double bonds - Unsaturated fatty acids exist in two isomeric forms: cis form (a) and trans form (b) In the cis-form, like groups are present on the same side In the trans-form, like groups are on the opposite sides The double bonds in most naturally occurring fatty acids are cis form Fatty Acids - Monounsaturated: one double bond - Polyunsaturated: have two or more double bonds Double bonds cause a “kink” in the fatty acid chain Melting Point of Fatty Acids - Saturated Fatty Acids have a higher melting point and are usually solid at room temperature - Unsaturated Fatty acids have a lower melting point and are liquid at room temperature - Increasing the number of double bonds further lowers the melting point Stearic Acid (18:0): MP= 69.6°C/156.7°F Oleic Acid (18:1Δ9): MP= 13.4°C/55°F Linoleic Acid(18:2Δ9,12): MP= -5°C/23°F 𝛼-Linoleic Acid (18:3Δ9,12,15): MP= -11.2°C/11.7°F Fatty Acid Abbreviation Using Regular Numbering System - Fatty acid abbreviation (18:1Δ9) (18:2Δ9,12) and (18:3Δ9,12,15): The number before the colon indicates the number of carbons in the fatty acid The number next to the colon indicates the number of double bonds in the fatty acid The superscript (Δ9,12,15) indicates the 1st, 2nd, and 3rd double bonds start at carbon number 9,12, and 15 respectively. Fatty Acid Abbreviation using 𝜔 Number System - Linoleic Acid (18:2𝜔-6) is 𝜔-6 fatty acid The # before the colon indicates the # of carbons in the fatty acid The # after the colon indicates the number of double bonds The number after the 𝜔 indicates the number of the carbon that the first double bonds starts from the 𝜔 carbon - 𝛼-Linoleic acid (18:3𝜔-3) is a 𝜔-3 fatty acid Essential and Nonessential Fatty Acids - Plants and bacteria synthesize all the required fatty acids Fatty acid synthesis requires acetyl-CoA - Animals acquire most of their fatty acids from dietary sources - Nonessential Fatty Acids: can be synthesized by animals - Essential Fatty Acids: Linoleic acid (Omega-6 Fatty Acids) and 𝛼-linolenic acid (Omega-3 Fatty acids) Mammals do not have enzymes to synthesize Linoleic acid and 𝛼-linoleic acid Must be obtained from the diet 𝜔-6 Fatty Acids - Linoleic Acid (18:2Δ9,12 or 18:2𝜔-6) is the precursor for numerous derivatives formed by elongation and/or desaturation reactions 𝛶-linoleic acid (18:3Δ6,9,12 or 18:3𝜔-6) Arachidonic acid (20:4Δ6,9,12 or 20:4𝜔-6) Docosapentanenoic (22:5Δ4,7,10,13,16 or 22:5𝜔-6) (DPA) - Food Sources: Vegetable Oils (sunflower and soybean oils), eggs and poultry 𝜔-3 fatty Acids -𝛼-linolenic acid (18:3Δ9,12,15 or 18:3𝜔-3) Eicosapentaenoic Acid (20:5Δ5,8,11,15,17 or 20:5𝜔-3) (EPA) Docosahexaenoic Acid (22:6Δ4,7,10,13,16,19 or 22:6𝜔-3) (DHA) -Sources: Flaxseeds, soybean oils, and walnuts EPA and DHA are also found in fish (salmon,tuna, and sardines), and fish oils -Health Benefits: Promote cardiovascular health Lower blood triacylglycerol level Lower blood pressure Decrease platelet aggregation Beneficial role of 𝜔-6 and 𝜔-3 Fatty Acids - Eicosanoids: Hormone-like molecules derived from 𝜔-6 and 𝜔-3 fatty acids Prostaglandin, Thromboxane and Leukotriene: smooth muscle contraction, blood flow regulation, inflammation, and pain perception 𝜔-6 derived eicosanoids promote inflammation 𝜔-3 derived eicosanoids function as anti-inflammatory 𝜔-6 and 𝜔-3 ratio in diet influence inflammatory and anti-inflammatory eicosanoids synthesis ^ Current healthy ratios believed to be 1:1 to 1:4 2.) Triacylglycerols - Triacylglycerols (Triglycerides) Esters of glycerol with 3 fatty acids Neutral fats, because they have no charge Contain fatty acids of varying lengths with mixture of saturated and unsaturated fatty acids - Monoacylglycerols/Diacylglycerols: Glycerides with 1 or 2 fatty acid groups (metabolic intermediates) Properties of Triacylglycerols - Depending on their fatty acid composition, the triacylglycerol can be termed as fats or oils Fats: solid at room temperature and have a high saturated fatty acid composition Oils: liquid at room temperature and have a high unsaturated fatty acid composition Properties of Triacylglycerols - Saponification: a process that produces soap While heating oil with KOH or NaOH, triacylglycerol is hydrolyzed to glycerol and Na or K salts of fatty acids (soap) The soap forms micelles in water, as fatty acids are amphipathic (with polar and nonpolar domains) The soap is an emulsifying agent Grease/oil drops dispersed in soap micelles 3.) Wax Esters - Waxes: complex mixtures of nonpolar lipids Protective coatings on the leaves, stems and fruits of plants and on the skin and fur of animals - In wax long-chain fatty acids esterified with long-chain alcohols Examples is bee wax Lecture 26: Lipid Structure and Classification 2 4.) Phospholipids - Phospholipids are amphipathic with a polar head group (phosphate and charged groups) with hydrophobic fatty acids When suspended in water, phospholipids spontaneously rearrange into ordered structures such as lipid monolayer, micelle and bilayer vesicles Phospholipids are vital for the cell membrane Phospholipids - Two types of Phospholipids:  Phosphoglycerides (Class-4) Sphingolipids (Class-5) - Phosphoglycerides: contain a glycerol, two fatty acids, a phosphate, and a alcohol Simplest phosphoglyceride is acid composed of glycerol-3-phosphate phosphatidic acid and two fatty acids Phosphatidylcholine (lecithin) is an example of alcohol esterified to the phosphate group with choline Phosphoglycerides (Class-4) → Phosphatidylcholine, Phosphatidylserine, and Phosphatidylglycerol - Phosphatidylcholine (PC) (Lecithin): major component of biological membranes Function as surfactant - Phosphatidylserine (PS): important component of biological membranes Act as a signal for macrophages to engulf the cells - Phosphatidylglycerol: present in lung Function as surfactant Present in amniotic fluid - is an indicator for fetal lung maturity Phosphatidylethanolamine and Diphosphatidylglycerol - Both Phosphatidylethanolamine and Diphosphatidylglycerol have relatively smaller polar heads and found in inner leaflet of membrane -Phosphatidylethanolamine is all called cephalin. It constitutes 25% of all phospholipids in humans. It is important for stabilizing the membrane curvature - Diphosphatidylglycerol is called cardiolipin. It is found in the mitochondrial inner membrane, where it constitutes 20% of the total lipid. It helps stabilize the ETC Phosphatidylinositol and Signaling Molecules - Phosphatidylinositol: present only in small amount (>1%) in membrane - Phosphatidylinositol-4,5-bisphosphate (PIP2) is an important precursor for DAG and IP3 DAG (Diacylglycerol) and IP3 (Inositol Triphosphate) are the signaling molecules Phosphatidylinositol and Protein Anchor - Glycerol Phosphatidylinositol (GPI)-linked protein - GIP is lipid anchor for many cell-surface proteins Phospholipid Digestion by Phospholipases - Phospholipases (PLA): hydrolyze the ester bonds in glycerophospholipid molecules PLA1: hydrolyze the ester bond at C1 of glycerol PLA2: hydrolyze the ester bond at C2 of glycerol PLB: hydrolyze both C1 and C2 ester bonds PLC: hydrolyzes the phosphodiester bond between glycerol and phosphate PLD: hydrolyze the phosphodiester bond between phosphate and fatty acid (i.e. R3) Use of Phospholipids - Cells coordinately use the phospholipases and acyltransferases to: Alter the membrane flexibility (also known as membrane fluidity) by replacing saturated vs. unsaturated fatty acids, and the length of the fatty acids Replace the damage fatty acids - Phospholipases: remove fatty acids from phosphoglycerides - Acyltransferase: add fatty acids to phosphoglycerides Sphingolipids (Class-5) - Sphingolipids constitute Sphingomyelin and Glycolipids -The core for for sphingomyelin and glycolipids is Ceramide Ceramide is composed of sphingosine and a fatty acid Ceramide is the fatty acid amide derivative of sphingosine Sphingomyelin - In sphingomyelin, the OH-group of ceramide is esterified to phosphate group of either phosphoryl-choline or phosphoryl-ethanolamine - Sphingomyelin is an important sphingolipid: It insulates the nerve cells It facilitates rapid transmission of nerve impulses Glycolipids - In glycolipids, monosaccharide, disaccharide, or oligosaccharide attached to ceramide through O-glycosidic bond Found on the extracellular face of eukaryotic cell membranes Function to maintain stability of the membrane Facilitate cell-cell interactions Act as receptor for virus and other pathogens to enter cells - Important Classes of Glycolipids: Cerebrosides Sulfatides Gangliosides Cerebrosides and Sulfatides - Cerebrosides: are sphingolipids in which the head group is a monosaccharide - Galactocerebrosides: found in the cell membranes of the brain - Sulfatides (Sulfated Cerebrosides) are negatively charged at physiological pH Gangliosides - Gangliosides: sphingolipids that possess oligosaccharide groups with one or more sialic acid residues Present in most animal cells and GM2 is involved in Tay-Sachs disease Isoprenoids (Class-6) - Isoprene: 5-carbon structura unit - Many biomolecules contain repeating isoprene units Two isoprene units joins to form mono terpene (used in perfume) Tetraterpenes (Carotenoids) Steroids are all the derivatives of triterpenes with 4 fused rings (e.g. cholesterol) Monoterpene and Sesquiterpene - 2 isoprene units join to form Monoterpene - 3 isoprene units join to form Sesquiterpene Tetraterpenes - Carotenoids are tetraterpenes Steroids - Steroids are all the derivatives of Triterpenes Lecture 27: Lipid Digestion, Absorption, and Biotransformation Dietary/Nutritional Fat - Know the steps for how fat is digested and absorbed in the small intestine Lipid Digestion in Intestine - Most of the dietary fat is triacylglycerols (TG) with small amounts of phospholipids and cholesterol -Dietary lipid digestion and absorption takes place in the intestine. -In the intestinal lumen, the dietary fat emulsified (solubilized) by mixing with bile salts to form micelles -Pancreas secretes pancreatic lipase and phospholipase A2 (PLA2) enzymes into the intestine The PLA2 digests the ester bond at C2 of the dietary phospholipids and release 1 free fatty acid and a lysophosphatidate The pancreatic lipase digests the ester bonds at C1 and C3 of the dietary triacylglycerols and release 2 free fatty acids and a monoacylglycerol Pancreatic Lipase Digests the Ester Bonds at C1 and C3 of the Dietary Triacylglycerols and Release 2 Free Fatty Acids and a Monoglyceride Pancreatic Phospholipase A2 (PLA2) digests the ester bond at C2 of the Dietary Phospholipids and release Lysophosphatidate, a Free Fatty Acid Lipid Absorption in Intestine - Free fatty acids (FFAs), monoacylglycerols, lysophosphatides and cholesterol form mixed micelles and absorbed freely into the intestinal cells Inside the cell, the FFAs are activated to form Acyl-CoA Inside the cell, 2 Acyl-CoA are reassembled with monoacylglycerol to synthesize triacylglycerol Inside the cell, the FFAs are reassembled with lysophosphatide to synthesize phospholipid Inside the cell, the newly synthesized triacylglycerols, phospholipids, cholesterol and ApoProtein-B48 are packaged to form nascent (newly made) chylomicrons - Short (C1-C5) and medium (C6-C12) chain FAs are absorbed directly into blood, where it dins to albumin and are transported to the liver Fatty Acid Activation by Coenzyme-A Triglyceride Synthesis Phospholipid Synthesis Chylomicron/Lipoprotein - Chylomicrons are also called lipoproteins Lipoproteins: composed of lipids, cholesterol, cholesterol esters and protein in different ratio Lipoproteins are found in blood Lipoproteins - Lipoproteins are classified according to their density. - Chylomicrons: Synthesized in the intestine Exogenous Fat Transport Pathway:Transports dietary fat (i.e. triacylglycerol and cholesterol) from intestine to other tissues - Very-Low-Density Lipoproteins (VLDL): Synthesized in the liver Endogenous Fat Transport Pathway: transports lipids from liver to other tissues - Intermediate-density Lipoproteins (IDL;VlDL- Remnants) Size: diameter