Fatty substance, separated from salifiable bases, was dissolved in boiling alcohol. It was crystallized and very pure, and in this state it was examined. One of its characters is to have the appearance of mother of pearl, which it communicates to several of the combinations of which it forms.
Fatty substance, separated from salifiable bases, was dissolved in boiling alcohol. It was crystallized and very pure, and in this state it was examined. One of its characters is to have the appearance of mother of pearl, which it communicates to several of the combinations of which it forms.
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Fatty substance, separated from salifiable bases, was dissolved in boiling alcohol. It was crystallized and very pure, and in this state it was examined. One of its characters is to have the appearance of mother of pearl, which it communicates to several of the combinations of which it forms.
Copyright:
Attribution Non-Commercial (BY-NC)
Available Formats
Download as PPT, PDF, TXT or read online from Scribd
The fatty substance, separated from salifiable bases,
was dissolved in boiling alcohol. On cooling, it was obtained crystallized and very pure, and in this state it was examined. As it has not been hitherto described I purpose to call it margarine (), from Greek word signifying pearl (), because one of its characters is to have the appearance of mother of pearl, which it communicates to several of the combinations of which it forms with the salifiable bases.
-Michel-Eugene Chevreul,
article in Philosophical Magazine, 1814 Lectured by Dr. Qin Yongmei (): June 2, 2007 Storage lipids
Roles of Lipids Energy storage (fatty acids, triacylglycerols) Structural elements (phospholipids, cholesterol) Hormones ( sex hormones e.g. Estrogen) Enzyme cofactors (coenzyme A) Electron carriers (coenzyme Q, plastpquinone) Light-absorbing pigments (carotenoids) Hydrophobic anchors (dolichols) Emulsifying agents (bile salts) Intracellular messengers (phosphatidyl inositol)
Storage lipids Fatty acids:
- Structure and nomenclature - Physical and chemical properties
Triacylglycerols:
- Structure - Function - Food Fatty acids Structure and nomenclature Basic formula: CH 3 (CH 2 ) n COOH Carboxylic acids with hydrocarbon chains of 4-46 carbons Free FAs are found in trace quantities in cells
FAs are either: (i) part of a lipid molecule (ii) complexed to a carrier protein (e.g. albumin on blood)
Saturated or unsaturated, usually linear Naturally occurring fatty acids There is a common pattern in the location of double bonds:
Unsaturated FA: 9 , 12 , 15
Polyunsaturated FA:
double bonds are never conjugated and are in the cis configuration
18:3 ( 9,12,15 ), -linolenic acid : octadecatrienoic acid (-3) Cis 9 Fatty acids #C Common Name 12 Lauric Acid 14 Myristic Acid 16 Palmitic Acid 16:1 Palmitoleic Acid 18 Stearic Acid 18:1 Oleic Acid () t18:1 Elaidic Acid () 18:2 Linoleic Acid 18:3 Linolenic Acid 20 Arachidic Acid 20:4 Arachidonic acid 24:0 Ligoceric Acid Essential Fatty acids Essential Fatty Acids Omega-3 (-3) and omega-6 (-6) fatty acids are unsaturated "Essential Fatty Acids" . The two EFAs are linolenic (-3) and linoleic (-6). The 3" and 6" indicate where the first double bond occurs in the fatty acid molecule. Example: DHA (docosahexenoic acid, C22:6 ) and AA (arachidonic acid, C20:4) are both crucial to the optimal development of the brain and eyes. Health consideration: In modern diets: -6 / -3 ratio = 15:1; Expected ratio: 2:1 to 4:1 reduced mortality from cardiovascular disease, suppressed inflammation in patients with rheumatoid arthritis (),and decreased risk of breast cancer. Fatty acids Physical and chemical properties Weakly acidic (pKa = 4.5 - 5), ionized at physiological pH
Saturated FAs (chain length > 8C) are solid at room temperature. Melting point (m.p.) depends on chain length, the degree of unsaturation
Cis double bonds disrupt intermolecular packing and therefore lower m.p;
Polyunsaturated FAs are readily oxidized by exposure to air.
Fatty acids form micelles. amphipathic () zig-zag kink Van der Waals interactions between the acyl chains: cis double bonds + Tm Fatty acids form micelles The assembly of micelles is driven by the hydrophobic effect Non-polar interior can dissolve hydrophobic compound What is soap ? TAG + 3KOH (NaOH) 3RCOO - K+ + glycerol FA chains can dissolve in oils while charged carboxyl group dissolves in water;
Forms a mixed micelle which can remove oils;
Soap form precipitates with divalent cations (reduces efficiency);
Detergent (modified FAs) do not precipitate with calcium, used as better cleaning agents. Triacylglycerols Structure: TAGs are fatty acid esters of glycerols, with each TAG made up of 1 glycerol and 3 FAs. Adipocyte Function:
TAGs are used as a stored fuel;
Advantages: (1) Greater energy yield
FA 9 kcal/g (37 kJ/g) CHO/protein 4 kcal/g (16 kJ/g)
(2) Lipid hydrophobicity
TAGs coalesce into dense droplets and exclude water
Triacylglycerols Triacylglycerols Example:
In a 70 kg person, the energy reserves are: 100,000 kcal TAGs 25,000 kcal protein (muscle) 600 kcal glycogen 40 kcal glucose
TAGs represent 11 kg of body weight (55 kg glycogen). TAG stores can last weeks to months, and glycogen stores exhausted less than one day. Fatty acids in food: saturated vs unsaturated Source Lauric/Myristic Palmitic Stearic Oleic Linoleic Beef 5 26-32 20-25 37-43 2-3 Milk 25 12 33 3 Coconut 74 10 2 7 Corn 8-12 3-4 19-24 34-62 Olive 9 2 84 4 Palm 39 4 40 8 Soybean 9 6 20 52 Sunflower 6 1 21 66 Fatty acid composition of three food fats Possible risks related to trans fatty acids 4 Major trans FA found in food: 18:1t (less amount of 16:1t and 18:2t)
4 Sources of tFA: margarine, cakes, cookies, chips etc.
4 Link tFA to breast cancer (http://www.sciencedaily.com)
4 Link tFA to increased serum cholesterol (http://cardiology.medscape.com http://nutrition.about.com) Hydrogenation of Natural Unsaturated Fats Purpose: a commercial chemical process to add more hydrogen to natural unsaturated fats to decrease the number of double bonds and retard or eliminate the potential for rancidity (). C C H H H H C C H H + H 2 high temperatures with metal catalysts Side effect: cause a large percentage of the natural cis double bonds to change to trans double bonds. cis Dietary fat and health Mainstream nutritional science has demonized dietary fat, yet 50 years and hundreds of millions of dollars of research have failed to prove that eating a low-fat diet will help you live longer
(Science 2001, 291:2536-2545)
Artificial fats (fat substitutes ) - mixtures of the esters of fatty acids with polyglycerol. R-[OCH 2 -CH(OR)-CH 2 O] n -R R: fatty acids; n: about 3. - almost completely metabolized like fats, so they are not calorie-free; - the polymerized glycerol moiety is not digested and is excreted primarily in the urine. Olestra: - an artificial fat created from sucrose (replace of glycerol) and up to eight fatty acids; - too large to be metabolized and passes through the body unchanged, but because it acts as a lipid, it can cause depletion of fat-soluble vitamins.
Polyglycerol fatty acid esters: Waxes Esters of long chain fatty acids (C14-36) with long chain (C16-30) alcohols
High melting points (60-100C)
Energy storage (Plankton, )
Water repellant (birds and plants) Triacontanoylpalmitate major component of beeswax Structural lipids in membranes
+ Phospholipids
+ Sphingolipids
+ Plant galactolipids and sulfolipids
+ Archaebacteria have unique membrane lipids
+ Cholesterol 29
Phospholipids
2 Classes of phospholipids (PL) (i) glycerolphospholipids glycerol backbone (ii) sphingomyelin spingosine backbone
Glycerolphospholipids - essential for membrane structure - most abundant membrane lipids - no genetic defects in humans
Sphingolipids sphingomyelin, neutral glycolipid and gangliosides L-Glycerol-3-phosphate (D-glycerol 1-phosphate), the backbone of phospholipids Glycerophospholipid Saturated FA
Unsaturated FA phosphatidic acid Phosphatidylethanolamine ethanolamine Phosphatidylcholine choline Phosphatidylserine serine
Some phospholipids have ether-linked fatty acids Other Phospholipids Plasmalogens found in central nervous system and in heart muscle vinyl either linkage at glycerol C-1 choline and etanolamine head groups resistant to phospholipases
Platelet activating factor active at very low concentration (0.1 nM) released from leukocytes called basophils cause platelet aggregation and vasoconstriction (via release of serotonin from platelets) involved in smooth muscle contraction inflammation, allergic response acetyl group makes it water soluble Sphingolipids sphingosine (4-sphingenine) 36
Sphingophospholipids
sphingosine Fatty acid phosphate Head group 2nd large class of membrane lipids
abundant in tissues of central nervous system
involved in recognition events at the cell surface, such as cell recognition & cell-cell communication
Ceramide (shingosine + FA) is the structural unit common to all sphingolipids 37 Glycolipids (e.g. cerebrosides and gangliosides) Various monosaccharides e.g. glucose, galactose sphingosine Fatty acid Carbohydrate Amphipathic, pack together with phospholipids in bilayers Similarities between phosphatidylcholine and sphingomelin Sphingolipids at Cell Surface are Sites of Biological Recognition The carbohydrate moieties define the human blood groups. Phospholipids and sphingolipids are degraded in lysosomes Inherited human diseases resulting from abnormal accumulation of membrane lipids Sphingolipid storage diseases Polar lipids of membrane undergo constant turnover;
Sphingolipids degraded in lysosomes;
Deficiency in particular enzyme leads to accumulation of a sphingolipid or breakdown intermediate ; High incidence (1/3600 births, 1/28 carriers defect gene in recessive form); Mental retardation and early death (2-3 years); Lipid accumulation causes lysosomes to swell leading to cellular/tissue enlargement; Swollen lysosomes in CNS tissue neuronal death. Sphingolipid storage diseases
Chloroplasts contain galctolipids and sulfolipids Galactolipids Sulfolipids one or two galactose residue are connected by a glycosidic linkage to C-3 of a 1,2-diacylglycerol (1,2-DAG) ; thylakoid internal membrane () lipid; they make up 70-80% of the total membrane lipids of a vascular plant, most abundant membrane lipid in the biosphere. Phosphate is missing ! A sulfonated glucose residue is joined to a 1,2-DAG; Sulfonate bears a negative charge (similar role of phosphate group in phospholipids). Archaebacteria contain unique membrane lipids
4 ether linkages Glycerol dialkyl glycerol tetraethers (GDGT) 8 five-carbon isoprene groups R Glycerol dialkyl glycerol tetraethers 4 The archaebacteria live in ecological niches with extreme conditions-high temperatures, low pH and high ionic strength;
4 Ether bonds in GDGT are more stable than ester bonds.
4 twice the length of phospholipid and sphingolipid;
4 with polar heads consisting of glycerol linked to either phosphate or sugar residues;
4 Central carbon of glycerol is in R configuration in archaebacteria, but in S configuration in the eubacteria and eukaryotes. 47 Lipids and structure of the plasma membrane glycolipid Polar head hydrophobic tail Integral protein cholesterol To minimize interactions of FA chains (non- poplar), phospholipids aggregates form a bilayer structure. Cholesterol Steroids: (i) cholesterol and sterols of plants and fungi (ii) steroid hormones (iii) bile salts
Roles of cholesterol in mammals (i) structural component of plasma membrane and modulates membrane fluidity (ii) precursor of steroid hormones and bile acids
Rarely found in plants, never in bacteria
Steroids and lipid vitamines can be classified as polyprenyl compounds Lipids as signals, cofactors, and pigments Phosphatidylinositols act as intracellular signals
Eicosanoids carry messages to nearby cells
Steroid hormones carry messages between tissues
Vitamins A and D are hormone precursors Phosphatidylinositols in cellular regulation P456 Eicosanoids () paracrine hormones; derived from arachidonic acid 3 classes: prostaglandins, thromboxanes and leukotrienes
Thromboxanes: produced by platelets (thrombocytes) and act in the formation of blood clots.
Leukotrienes They are able to lure white blood cells to the site of injury and bind them to the vessel wall. But, overproduction of leukotrienes cause asthmatic attacks Metabolism of Natural C20 Cis Fatty acids Produces Powerful Eicosanoids.
Arachidonic acid (-6) Eicosapentaenoic acid (-3) Cyclooxygenase Lipoxygenase prostacyclins prostaglandins thromboxanes leukotrienes Hydroxy FAs Eicosanoids - In the late 1950s, Dr. Bergstrm purified the first prostaglandins and determined their structures.
-Bergstrms student, Dr. Samuelsson is responsible for the chemical development including determination of more significant components (e.g. leukotriene) within system. He could tell us how this system is built up and help us to understand the relationship between its various components.
- Dr. Vanes contribution was the discovery of an important component of the system-prostacyclin and revealed the secret mechanism behind the drug, acetylsalicylic acid (inhibition of the formation of prostaglandins)
The Nobel Prize in Physiology and Medicine 1982 "for their discoveries concerning prostaglandins and related biologically active substances" Sune K. Bergstrm Bengt I. Samuelsson John R. Vane Sweden Sweden United Kingdom b.1916 b.1934 b.1927 Cyclooxygenase (COX), also called prostaglandin H 2 synthase (bifunctional enzyme):
- cyclooxygenase activity; - peroxidase activity cyclooxygenase activity of COX cyclooxygenase activity of COX peroxidase activity of COX Aspirin and Ibuprofen belong to Non- steroidal anti-inflammatory drugs ,NSAIDs . Ibuprofen inhibits the same step, probably by mimicking the structure of the substrate or an intermediate in the reaction.
Aspirin inhibits the cyclooxgenase activity of COX by acetylating an essential Ser residue on the enzyme. Steroid hormones carry messages between tissues -Derivates of sterols;
-Play important roles in gene expression;
-Sex hormones and hormones from adrenal cortex;
-Prednisolone and prednisone are steroid drug with potent antiinflammatory activities. Plant: use steroids and eicosanoid-like compounds in signaling derived from fatty acid C18:3 ( 9,12,15 ) Plant defense Growth regulator 63 Vitamins Fat soluble: vitamins A,D,E,K Long chain polyunsaturates hydrocarbons attached to 1 or 2 benzene rings Vitamin A (retinol)
stored in liver precursor: carotene deficiency: night blindness
Vitamin D formed from precursor in skin by UV regulates Ca deposition deficiency: rickets Active sugar precursors Vitamin D 3 production and metabolism UV light 1,25-Dihydroxycholecalciferol Cholecalciferol (VitD 3 ) 7-Dehydrocholesterol 2 steps in skin 1 step in liver 1 step in kidney 25 Active VitD 3 Vit D 3 is formed in skin;
1,25-dihydroxy VitD 3 is biological active;
1,25-dihydroxy VitD 3 regulate gene expression, e.g. turning on the synthesis of an intestinal Ca 2+ binding protein;
Deficiency in VitD 3 Vitamins E and K and Lipid Quinones are oxidation-reduction cofactors
Vit E: biological antioxidants;
Vit K: undergoes a cycle of oxidation and reduction; during the formation of active prothrombin;
Warfarin: synthetic compound that inhibits the formation of active prothrombin;
Ubiquinone (coenzyme Q) and plastoquitone: isoprenoids that function lipophilic electron carriers in the oxidation-reduction reactions that drive ATP synthesis in mitochondria and chloroplasts, respectively.
The Nobel Prize in Physiology and Medicine 1943 "for his discovery of vitamin K" Henrik Carl Peter Dam Edward Adelbert Doisy Denmark USA 1895-1976 1893-1986 "for his discovery of of the chemical nature of vitamin K" Separation and Analysis of Lipids Lipid extraction requires organic solvents
Adsorption chromatography separates lipid of different polarity
Gas-lipid chromatography resolves mixture of volatile lipid derivates
Mass spectrometry
Specific hydrolysis chloroform/methanol/water water liver methanol/water chloroform Thin-layer chromatography adsorption chromatography NaOH/methanol Fatty acyl methyl ester Gas-liquid chromatography HPLC Determination of the structure of a fatty acid by mass spectrometry fatty acyl picolinyl () ester m/z Summary FAs and TAGs: nomenclature,structures and names of all common FAs; know the essential FAs; physical properties; structure of TAGs; advantages of TAGs as a fuel source structure of waxes
Glycerolipids: chemical structures of all the main phopholipids, including plasmalogen and platelet activating factor; nomenclature: you should know the general names (e.g. phosphatudylcholine), specific names (e.g. 1-palmitoyl-2 -oleoyl-phosphatidylcholine) and abbreviation (PC) head group charge phospholipase Summary Sphingolipids: structures of sphingosine, ceremide and sphingomyelin; families of sphingolipids; understand glycolipid storage disease;