Lipids - Structure & Function PDF

Lipids – Structure & Function in Biological 1  Biological functions of lipids  Energy source - lipids provide 9 kcal of energy per gram  Energy storage – triglycerides in adipocytes  Structural components of cell membrane - phosphoglycerides, steroids & sphingolipids  Hormo...

Lipids – Structure & Function in Biological 1  Biological functions of lipids  Energy source - lipids provide 9 kcal of energy per gram  Energy storage – triglycerides in adipocytes  Structural components of cell membrane - phosphoglycerides, steroids & sphingolipids  Hormones – steroids are critical intercellular messengers  Lipid-soluble vitamins (A, E, D, K)  Dietary fat acts as a carrier of lipid-soluble vitamins into cells of small intestine  Provide shock absorption and insulation 2  Classification of lipids Four Main Groups:  Fatty Acids – Saturated & Unsaturated  Glycerides – glycerol-containing lipids  Nonglyceride lipids – Sphingolipids, Steroids, & Waxes 3 Classification of lipids - Scheme 4  Fatty acids  Non branched long straight-chain of an even number of carbon atoms & a carboxyl group (−COOH). It is that carboxyl group that makes it an acid (carboxylic acid)  Most common chains range from 10 to 20 carbons in length 5  Structure  Stearic acid - a typical saturated fatty acid with 18 carbons in the chain  Oleic acid - a typical unsaturated fatty acid with 18 carbons in the chain 6  Saturated & unsaturated fatty acids  Saturated fatty acids don’t contain double bonds  Unsaturated fatty acids do contain double bonds Double bonds lower the melting temperature - The cis configuration doesn’t allow fatty acids to pack as close together 7  Unsaturated fatty acids  An unsaturated fatty acid has one or more carbon-carbon double bonds in the chain  The first double bond is usually at the ninth carbon  The double bonds is usually a cis- configuration 8 Unsaturated fatty acids - Examples 9  Properties of fatty acids  Melting point increases with increasing carbon number  Melting point of a saturated fatty acid is higher than an unsaturated fatty acid with the same number of carbons  Typical saturated fatty acids are tightly packed together  cis double bonds prevent good alignment of molecules in unsaturated fatty acids leading to poor packing (Oil vs. butter)  Double bonds lower melting point relative to saturated acid 10 Common fatty acids 11  Esterification of fatty acids Esterification - fatty acids react with alcohols to form esters and water 12  Hydrolysis of fatty acids Acid Hydrolysis - reverses esterification & fatty acids are produced from esters 13  Saponification of fatty acids Saponification - base-catalyzed hydrolysis of an ester & the products are:  An alcohol & an ionized salt which is a soap Soaps have a long uncharged hydrocarbon tail Also have a negatively charged carboxylate group at end Form micelles that dissolve oil and dirt particles 14 Soap & micelles formation 15  Reaction at the double bond  Hydrogenation – a addition reaction  unsaturated fatty acids may be converted to saturated fatty acids by a simple hydrogenation reaction  Hydrogenation is used in the food industry: Hydrogenation converts vegetable oils fromliquids to solids  Margarines are "hardened" this way 16  Eicosanoids: Prostaglandins, Leukotrienes, & Thromboxanes  Essential fatty acids - can’t be synthesized by the body Linoleic acid - essential fatty acid required to make arachidonic acid  Arachidonic acid (20 C) is the eicosanoid precursor  Eicosanoids are three groups of structurally related compounds Prostaglandins (PG) 17  Prostaglandins (PG)  Potent biological molecules produced in most tissues  they act like hormones in controlling the body’s processes. Structural they are: Synthesized from 20-carbon unsaturated fatty acids Cyclic compounds including a 5-carbon ring  Exert their effects on cells that produce them and cells in the immediate vicinity 18 Prostaglandin synthesis from Arachnoid Acid 19  Aspirin & Prostaglandins Aspirin inhibits prostaglandin synthesis by acetylating cyclooxygenase, an enzyme necessary for prostaglandin synthesis 20  Biological processes regulated by Eicosanoids 1. Blood clotting – Thromboxane A2 stimulates constriction of blood vessels & platelet aggregation – Prostacyclin dilates blood vessels and inhibits platelet aggregation 2. Inflammatory response – PGE2 mediates aspects of inflammatory response 3. Reproductive system 21  Biological processes regulated by Eicosanoids 4. Gastrointestinal tract – Prostaglandins inhibit gastric secretion – Prostaglandins increase secretion of protective mucus 5. Kidneys – PGE1-2 dilate renal blood vessels increased water & electrolyte excretion 6. Respiratory tract – Leukotrienes promote the constriction of bronchi 22 – Thromboxane & Leukotriene structure Oxygens have moved into the ring Note the 3 conjugated 23 bonds  Glycerides Glycerides are lipid esters  Alcohol group of glycerol form an ester with a fatty acid  Esterification may occur at one, two, or all three alcohol positions producing a monoglyceride, a diglyceride, or a triglyceride respectively A neutral triacylglycerol or a triglyceride Triglycerides are nonionic and nonpolar 24 Glycerides 25 Glycerides 26  Fats & Oils  Triglycerides or triacylglycerols Fats are a combination of glycerol and the fatty acids(esters)  Fats mainly come from animals, unless from fish, and are solid at room temperature  Oils mainly come from plants, and are liquid at room temperature 27  Phosphoglycerides  Phospholipid is a general term for any lipid containing phosphorus  Phosphoglycerides contain: Glycerol Fatty acid Phosphoric acid with an amino alcohol  Replace an end fatty acid of a triglyceride with a 28  Phosphoglycerides  Have hydrophobic and hydrophilic domains  Structural components of membranes  Emulsifying agents - soluble in both fat and water  Suspended in water, they spontaneously rearrange into ordered structures: Hydrophobic group to center Hydrophilic group to water Basis of membrane structure 29  Types of Phosphoglycerides  The phospho-amino-alcohol is highly hydrophilic  They are used in: Cell membranes Emulsifying agents Micelle-forming agents in the blood  Two types: Made with choline are called lecithin 30 Types of Phosphoglycerides 31  Nonglyceride lipids - Sphingolipids  The structural features of these lipids are based on sphingosine Long-chain Nitrogen-containing Alcohol  Amphipathic, like phospholipids Polar head group Two nonpolar fatty acid tail  Structural component of cellular membranes with two major categories: 32  Types of Sphingolipids - Sphingomyelins  Structural lipid of nerve cell membranes - Myelin sheath feature  Consist of fatty acid, phosphoric acid, choline (phosphocholine) and a complex amino alcohol (sphingosine)  No glycerol is present 33  Types of Sphingolipids - Glycosphingolipids  Built on a ceramide. They are sphingolipids that contain monosaccharides attached by a β-glycosidic bond to the –OH group of ceramide  Cerebrosides - single monosaccharide head group (Glucocerebroside & Galactocerebroside) 34 Sphingolipid storage diseases 35  Steroids All steroids contain a steroid nucleus, which consists of:  Three cyclohexane rings and one cyclopentane ring, fused together  The rings are designated as A, B, C, and D  Numbered carbon atoms beginning in ring A  Side chains make each steroid unique 36  Steroids - Cholesterol  The most abundant steroid in the body  A precursor of steroid hormones (progesterone, testosterone, estradiol)  A precursor of adrenocortical hormones (cortisol)  A precursor of bile acids - Important in the lipid digestion  A precursor of vitamin D 37 Steroids - Examples 38  Steroid hormones The adrenal cortex secrets different types of hormones - Adrenocorticoids  Mineralocorticoids - aldosterone regulate ion concentrations  Glucocortiods - cortisol enhance carbohydrate metabolism 39 Symptoms of high Cortisol levels 40  Waxes  Waxes are esters (R-COO-R’) formed from long-chain fatty acid and a long-chain alcohol (instead of glycerol)  The longer the chains, the higher the melting point  Protects the skin of plants and fur of animals  Examples of waxes include Beeswax & Carnuba (wax palm ) 41  Complex lipids - Lipoproteins Complex lipids are bonded to other types of molecules  Molecular complexes found in blood plasma containing: Neutral lipid core of cholesterol esters and TAGs Surrounded by a layer of:  Phospholipid  Cholesterol 42  Major classes of lipoproteins - Chylomicrons  The largest lipoproteins (180 to 500 nm in diameter)  Synthesized in the ER of intestinal cells contain 85 % of TGs (it is the main transport form of dietary TGs)  Deliver TGs from the intestine (via lymph and blood) to tissues (muscle for energy, adipose for storage) 43 Major classes of lipoproteins - VLDL Very Low Density Lipoproteins:  Formed in the liver & contain ~50-60 % of TGs and 22 % of cholesterol  The main transport form of TGs synthesized in the organism (liver)  Deliver the TGs from liver to peripheral tissue (muscle for energy, adipose for storage) 44 Major classes of lipoproteins - LDL Low Density Lipoproteins (Lethal):  Formed in the blood & liver from IDL (Intermediate density lipoproteins)  Enriched in cholesterol and cholesteryl esters (~ 50 % of cholesterol)  Major carrier of cholesterol to peripheral tissues  Less proteins  referred as “bad cholesterol”  depositing cholesterol within arteries 45 Major classes of lipoproteins - HDL High Density Lipoproteins (Healthier, good cholesterol):  Formed in the liver and partially in small intestine  Compared to LDL, HDL contain great amount of proteins (40%)  Pick up the excess of cholesterol from 46 Major classes of lipoproteins – HDL vs. LDL  High serum levels of cholesterol cause disease and death by contributing to development of atherosclerosis  The ratio of LDL/HDL cholesterol can be used to evaluate susceptibility to the development of atherosclerosis 47 Model structure of a plasma lipoproteins 48  Digestion & Absorption - Bile  Produced in the liver, stored in gallbladder, doesn’t contain enzymes  Alkaline solution composed of: bile salts, cholesterol, lecithin, & bile pigments (bilirubin)  Are secreted in the duodenum to emulsify triacylglycerol (TG) into fat droplets mechanical digestion - detergent action  breaks large fat globules into smaller fat droplets 49  Digestion & Absorption  Pancreatic lipase - secreted from the pancreas. It hydrolyzes T.G. to monoglycerides & free fatty acids Hydrolyzes off 1st and 3rd F.A. from T.G. Leaves the middle F.A.  Absorbed by intestinal epithelial cells  Reassembled into T.G.  Combined with proteins to form chylomicrons  Chylomicrons transport T.G. to adipocytes 50  Micelles A micelle formed from phospholipid lecithin: hydrophilic head regions (spheres) in contact with surrounding solvent sequestering the hydrophobic F.A. tail (straight lines) regions in the micelle center (oil-in-water micelle) 51 Digestion – An overview Insert fig 23.3 and caption 52  Chylomicron formation Intestinal cells:  Absorb lipids from micelles  Re-synthesize T.G.  Package with proteins to form chylomicrons  Chylomicrons 53 Chylomicron exocytosis & lymphatic uptake  Golgi packages chylomicrons into secretory vesicles  released from basal membrane by exocytosis  Vesicles enter the lacteal (lymphatic vessels of the small intestine), lymphatic cavity 54  Lipid storage  TG stored in cytoplasm of adipocytes  When energy is needed  hydrolysis of TG to FFA  transported to the mitochondrial matrix where they are degraded by β-oxidation after activation 55  β-oxidation β-oxidation is the sequence of a repetitive four reactions necessary for the degradation of the activated FA (Acyl CoA) in the mitochondria  Oxidation by flavin adenine dinucleotide (FAD)- dependent dehydrogenase  Hydration  Oxidation by flavin nicotinamide adenine dinucleotide (NAD)-dependent dehydrogenase  Thiolysis by coenzyme A The reaction is called β-oxidation because the 56  Before β-oxidation – Activation reaction  F.A. must first be converted to an active intermediate before they can be catabolized, accomplished in two steps  The only step that requires energy from ATP  high-energy thioester bond is formed between CoA & F.A.  Fatty acyl CoA 57  Crossing to the mitochondrial matrix  Fatty acyl CoA reacts with carnitine (carrier molecule) producing acyl-carnitine & coenzyme A  Enzyme carnitine acyltransferase I  Acyl-carnitine crosses into the mitochondrial matrix via a carrier protein located in the mitochondrial inner membrane  Fatty acyl CoA is regenerated once in the matrix, in another trans-esterification reaction catalyzed by carnitine acyltransferase II 58  β-oxidation – Step 1 Oxidation proceeds by removing H from the FA  Hydrogen reduces FAD to FADH2  Acyl-CoA dehydrogenase enzyme  results in formation of a trans double- bond “C=C” between C2 and C3 of the 59  β-oxidation – Step 2 Hydration, addition of water, across the double bond  The hydration occurs on the β- carbon  Catalyzed by enoyl-CoA hydratase  Normal reaction converts trans- 60  β-oxidation – Step 3 Hydroxylated β-carbon is dehydrogenated  NAD+ is reduced to NADH  NADH produces 3 ATP  Enzyme is L-β-hydroxyacyl-CoA dehydrogenase 61  β-oxidation – Step 4 Final reaction cleaves 2-C unit releasing acetyl CoA  3-ketoacyl CoA is cleaved into acetyl CoA and acyl CoA with β-ketoacyl thiolase (Thiolysis: attack of coenzyme A on β -carbon)  The reaction continues till all the atoms of the acyl CoA chain are broken into two carbon- acetyl CoA molecules  Each step produces  acetyl CoA & 2C- shorter fatty62  β-oxidation of subsequent Acetyl units  The shortened fatty acyl CoA is oxidized until chain is degraded to acetyl CoA  Acetyl CoA enters the tricarboxylic acid cycle (TCA/Krebs cycle) Each acetyl CoA during b-oxidation produce 12 ATPs from TCA 63 Complete oxidation of Palmitic Acid  FA Activation (before β-oxidation) Palmitic acid to Palmityl-CoA -2 ATP  β-oxidation (Steps 1-4 ) 7 FADH2 x 2 ATP/FADH2 14 ATP 7 NADH x 3 ATP/NADH 21 ATP  8 Ac-CoA (to TCA cycle) 8 x 1 GTP x 1 ATP/GTP 8 ATP 8 x 3 NADH x 3 ATP/NADH 72 ATP 8 x 1 FADH2 x 2 ATP/FADH2 16 ATP NET 64 129 ATP Cycles of β-oxidation - Overview 65 β-oxidation of Myristic acid - Example ???? 66  The End… 67