Lipids

Lehninger Principles of Biochemistry Fourth Edition David L. Nelson and Michael M. Cox Chapter 10: Lipids Copyright © 2004 by W. H. Freeman & CompanyBiological Importance 1. Fats & oilsstorage lipids 2. Phospholipids & sterolsstructural lipids 3. Others i. Cofactors ii. Electron carriers iii. Light-absorbing pigments iv. Hydrophobic anchors for proteins v. “chaperone” to help membrane protein fold vi. Emulifying agents in digestive tract vii. Hormones viii. Intracellular messenger1. STORAGE LIPIDS • Fats & Oilsderivatives of fatty acids (FA) – FAhydrocarbon triacylglycerols derviatives like fossil fuel – Burn them exergonic reaction – Two example: triacylglycerols and waxesFatty Acids • FA=Carboxylic acid + hydrocarbon chain(HC) – HCbetween 4-36 carbon long (C4 to C36) – Saturated HCno double bond – Unsaturated HCone or >one triacylglycerols – A few has OH, methyl-group branch, ringsNomenclature of FA • Palmitic Acid wth 16C, saturated: 16:0 • Oleic Acid wth 18C, one double: 18:1 • To show the position of double bonds triacylglycerols – D (delta) used: How? Dno of Catom • Example: # of C=20; # of DB=2, where? between C-9&C-10 C-12&C-13 SO 20:2 (D9,12)triacylglycerolsCommon • most monounsaturated FAD9 • Most polyunsaturated FAD9,12 or D9,15triacylglycerolscis-configuration highly common Trans-configuration: produced by microp of rumen of ruminants And during the hydrogenation of fish and vegetable oils triacylglycerols Trans FALDL (bad cholesterol)Physical properties Depending on # of Carbon & # of double b. The more hydrocarbonthe more hydrophobic The fewer double bondthe more hydrophobic triacylglycerols The more hydrocarbonthe more melting point The higher double bondthe lower melting pointtriacylglycerolstriacylglycerolstriacylglycerolsMelting • No double bond – Atoms close each other – Possibility of van der Waals triacylglycerols • Size – Carboxyl side is polar; polar/hydrocarbon • Double bond number – Not enough, cis configuration (kink)Triacylglycerols triacylglycerolsTypes of triacylglycerols • Simple triacylglycerols: only one kind of fatty acids (example: 16:0tristearin) • Mixed triacylglycerol (mostly): 2 or more triacylglycerols different fatty acids. • Triacylglycerolsnonpolar • Lipidslower speicifc gravity than water 2 layers water oilRoles of Triacylglycerols • Store energy • Insulation • Stored in cell as oily droplets serving as depots of triacylglycerols metabolic fuel – adipocytes for vertebratesfat droplets – As oil in seeds of plants • Lipases: enzyme to hydrolyse TA to fatty acids to be transported anywhere as an energy batterytriacylglycerolstriacylglycerolsWhy body uses TA to store energy • More reduced than sugartwice energy when hydrolysed • Hydrophobicunhydratedless space but triacylglycerols higher energy (2 g water/1 g polysaccharide to hydrate it) – 15 kg TA months – Full glycogen depots supply less than one day’s energyTA for insulation • TA under skinlow temperature – Seals, walruses, penguins etc triacylglycerols (warm-blooded polar animals) full of TA – Hibernating animals (bear) both energy and insulationtriacylglycerolsSimple and mixed TA in food. So different FA in size and saturation degree triacylglycerolsWaxes WaxesWaxes• Function of waxes depends on • Waxes are water repellent • Firm consistency • Waxes for hairpliable (easy to bend), lubricated, waterproof Waxes • Birds’ feather • Tropical plants’ leaves for water loss • Industeial usage • Ointments, lotions and polishes from waxes Structural lipids in Membrane • A barrier • A double layer of lipids • Amphipatic (charged and hydrophobic)I II III IV V Called Phospholipid Called glycolipid Why? Polar group to hydrophobic moeity by Phosphodiester bond Why Sugar at polar head1. Glycerophospholipid GlycerophospholipidGlycerophospholipidGlycerophospholipidFatty Acids • Glycerophospholipid Fatty Acids • Differences in different organism, tissues, even cells Glycerophospholipid • Generally – C-1 to C16 or C18 – C-2 to C18 or C20Phospholipids with ether linked fatty acids: Ether lipids Ester •Vertebrate heart tissue (plasmalogen%50 of phospholipids) •Halophilic (salt lovers) bacteria •Cilliated protists •Certain invertebratesGalactolipids : plants (most abundant) Localized in thylokoid membrane in chloroplast Make up 70-80% of total membrane lipid No phosphate intake Plants also have sulfolipids (sulfonated glucose to a diacylglycerol in glycosidic linkage) -1Archeabacteria’s membrane lipids (Hydrocarbon) Glycerol dialkyl glycerol tetraethers (GDGTs)Sphingolipids •4th biggest group •Polar head + 2 nonpolat tail •No glycerol •Majority no phosphate group •Extra sphingosine •Its strucutre: 1 sphingosine + 1 FA + head• Three subclass of sphingolipids 1. Sphingomyelins 2. Glycosphingolipids 3. Gangliosides• Three subclass of sphingolipids 1. Sphingomyelins – Phosphocholine (polar head group –X) – So called glycerophospholipid (due to phosphate group) – Animal cells – Prominent in myelin sheat around axons 2. Glycosphingolipids 3. Gangliosides• Three subclass of sphingolipids 1. Sphingomyelins 2. Glycosphingolipids – Generally outer face of plasma membrane – Sugar (1 or 2) to ceramidine wthout phosphate g. – Cerebroside: single sugar – Glucosenonneural tissue – Galactoseneural tissue – Globosides: neutral – 2 or more sugar – D-glucose; D-galactose; N-acetyl-D-galactosamine 3. Gangliosides• Three subclass of sphingolipids 1. Sphingomyelins 2. Glycosphingolipids 3. Gangliosides – most complex one – Oligosaccharide + N-acetylneuraminic acid (sialic acid) – Negative charge due to sialic a. – Accumulated in outer surface of plasma membrane – Kinds and amount change during developmentDegraded in lysosomesSterols • With steroid nucleus ( 4 fused rings; 3X6+1X5) – Planar – Rigid – No rotation – Most eukaryotics’ membrane – Plant can synthesize – Animals can do – But bacteria can not (a few exception) – Funciton: some in signaling, in the structure of bile acids (cholestrol)Lipids with active role passive role 1. Potent signals (hormones) 2. Enzyme cofactor (in cellular respiration and photosynthesis and in transfer of sugar moeties) • Vitamines –A, D, E ,K 3. Pigment molecules (to absorb light to see (eye) or to produce chemical energy (leaf), colorization (orange of carrot) 4. volatile lipids (communication of plants)Phosphatidylinositol: Regulate metabolism •Phosphatidylinositol and its phosphorylated derivatives: phosphatidylinositol 4,5-bisphosphate inositol 1,4,5-trisphosphate (IP3) •some regulatory proteins binds to phosphatidylinositol 3,4,5-bisphosphate •source of intracellular messengers. Eicosanoids • Paracrine hormone (near point) • involved in – Reproduction – inflammation – Pain – Fever – Formation of blot clots – Regulation of blood pressure – Gastric acid segration – Etc• Prostaglandins: prostate gland – Two known groups – PGE ether-soluble (subgroups PGE1 ...) – PGF water soluble – Regulation of cAMP • Regulation of celular and tissue functions• Thromboxanes – By thrombocytes • In blood clotting• Leukotrienes – in leukocytes – Powerful signals – leukotriene D4, contraction of the muscle lining the airways to the lung. – Overproductionasthmatic attacks – strong contraction of smooth m. of lung (anaphylactic shock) potentially fatal allergic reaction in individuals hypersensitive to bee stings, penicillin, or other agentsSteroid hormones • derivatives of sterols – lack alkyl chain attached to D ring of cholesterol • SHproducedblood streamenter cellbinds to proteinprotein expression • [low]enough because of its ­affinity • major Steroid hormones: – sex hormones, – hormones from adrenal cortex: • cortisol, aldosteronemale sex hormone organ: testis female sex h ovary and placenta regulation of glucose metabolism regulation of salt extraction both from adreanl cortex synthetic drug for inflammation potent growth regulator in vascular plantsVolatile Signals • lipophilic compound for plant to….. – attrack pollinators and helpful organisms against enemies – repel herbivors – communicate with friends – exmple: josmante Vitamins • vitamins essential (mostly not produced by animals, most in diet) • grouped into two – soluble in polar s. (water-soluble vitamins) – soluble in nonpolar solvent(fat-soluble v) • A,D,E,K: isoprenoid compounds by condansation of poly-isoprene unitsVitamin D3 • cholecalciferol – from skin from 7-dehydrocholesterol • ultiately converted to 1,25-d,hydroxyvitamin D3 – hormone which regulates …….. • calcium uptake by intestine • calcium level in kidney and bones – interact directly with its target protein in nucleus • deficincy defective bone formation and rickets • vitamin D2by yeast and similar effect like D3 – added into milkVitamin A • retinol • various forms functioning as….. – hormone such as retinoic acid • receptor of cell nucleus to regulate gene in epithelial cell development – visual pigment as retinal • initiate response of rop and cone to light • sources: fish oil, liver,egg,milk, butter • beta-carotene: pigments that gives carrots, sweet potatoes, yellow veetables • Syptoms:dryness in skin,eyes and mocous, night blidness•Tocopherols •Aromatic ring + along isoprenoid side chain •Hydrophobic so associate with •Cell membrane •Lipid droplets •Lipoproteins •Antioxidant because of its aromatic ring •Sources: egg, vegetable oil, white germ •Deficiencyrare; symp: RBC fragility•A cycle of oxidation & reduction during the formation of active protrombin •active protrombin: an enzyme converting fibrinogen to fibrin • fibrin: insoluble protein holding bloot clot together •Deficiencyrare; only in new borns •Source: green plants, K2 intestinal bacteriaWorking with Lipids • First degradation – Alkali – Acidic – Hydrolytic enzymes • Glycosidase • phospholipaseWorking with Lipids • Extraction – Neutral lidips (TG, waxes)by the solvents • Ethyl ether, chloroform, benzen (hydrophobic) – Membrane Lidips by more polar solvents • Ethanol, methanol – Example: chloroform, ethanol, water (1:2:0.8) – Then add water » Two layers:lipids in chloroformSeperation by.. •Adsorption chromotography •Silica gel: polar but insoluble •Polar lipidsadsorb to silica gel •Neutral Lipidseluted •To remove polar lipidspolar solvents: •For polar, uncharged:acetone •Charged: methanol •TLC:•Very similar to Ad. Ch. •Plate with silica •Neutral lipids run faster •Trick in staining lipids •Spray(a dye: RHODAMINE) •Đodine fumes: yellow-brown •Đnteract with double bond •Other commercials