lipid biochem - Lipid • general characteristics • fatty...

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Unformatted text preview: Lipid • general characteristics • fatty acids – nomenclature • biological active lipids – – – steroid hormones intracellular signaling eicosanoids • structural lipids – triglycerides • energy storage • fat soluble vitamins – vitamin A – Vision biochemistry – wax • protective coating – membrane lipids • phospholipids • sphingolipids • sterols Lipids’ general characteristics • • • insoluble in water diverse in structure and function fats and oils are the principal stored forms of energy • phospholipids and cholesterol contribute to 50% of plasma membrane mass • other important functions of lipids – signal transduction, enzyme cofactors, electron carriers, hormones, light-absorbing pigments, lighthydrophobic anchors 1 Fatty acids • fatty acids are carboxylic acids with hydrocarbon chains of 4 to 36 carbons – most commonly occurring fatty acids have even numbers of carbons atoms • hydrocarbon chains can be – fully saturated (contains no double bond) or unsaturated – mostly unbranched – may contain three carbon rings or hydroxyl groups • free fatty acids circulate in blood bound to a protein carrier, serum albumin Nomenclature of fatty acids • -noate • number of carbons – 18C (no double bonds) –1 –2 –3 a -> e -diendien-trientrienoctadecanoate • number of double bonds octadecenoate octadienoate octatrienoate • position and configuration of double bonds – cis Δ 9 octadecenoate 9,12 – all cis Δ 9,12 octadecadienoate 9,12,15 – all cis Δ 9,12,15 octadecatrienoate 2 O O C O O C O O C CH3 CH3 H3C Stearate Oleate Linolenate Structures of three fatty acids. a. Stearate (octadecanoate), a saturated fatty acid. b. Oleate (cisΔ9-octadecenoate) a monounsaturated fatty acid. c. Linolenate (all cis-Δ9, 12, 15-octadecatrienoate), a polyunsaturated fatty acid. cis double bonds produced kinks in the backbone of the unsaturated fatty acids. Nomenclature of fatty acids • • • • • • • C1 C2 C3 C4 C5 C6 last carboxyl carbon α β γ δ ε Cω 3 Fatty acids structure Fatty 1 O O C α β δ 2 e.g. Fatty acid HC CH CH2 3 3 γ4 ε6 5 7 Fatty acyl group Hydrocarbon tail ω 3 double bond 8 9 10 11 ω CH 3 12 ωCH Melting points of fatty acids • affected by – chain length: longer chains have higher melting point (C18 > C16) – double bond: more double bond means less compact and lower melting point 9,12 (cis Δ 9 octadecenoate > all cis Δ 9,12 octadienoate > all cis 9,12,15 Δ 9,12,15 octatrienoate) – double bond configuration: fatty acids with cis double bond packs more regularly than trans double bond, therefore have higher melting points (cis Δ 9 octadecenoate > trans Δ 9 octadecenoate) 4 Common fatty acids in membrane lipids Number Number Common name of of double carbons bonds 12 14 16 18 20 22 24 16 18 18 18 20 0 0 0 0 0 0 0 1 1 2 3 4 Laurate Myristate Palmitate Stearate Arachidate Behenate Lignocerate Palmitoleate Oleate Linoleate Linolenate Arachidonate IUPAC name Melting Molecular struture points, oC CH3(CH2)10COOCH3(CH2)12COOCH3(CH2)14COOCH3(CH2)16COOCH3(CH2)18COOCH3(CH2)20COOCH3(CH2)22COOCH3(CH2)5CH=CH(CH2)7COOCH3(CH2)7CH=CH(CH2)7COOCH3(CH2)4(CH=CHCH2)2(CH2)6COOCH3CH2(CH=CHCH2)3(CH2)6COOCH3(CH2)4(CH=CHCH2)4(CH2)2COODodecanoate Tetradecanoate Hexadecanoate Octadecanoate Eicosanoate Docosanoate Tetracosanoate cis-Δ9-Hexadecenoate cis-Δ9-Octadecenoate cis,cis-Δ9,12Octadecatrienoate all cis-Δ9,12,15Octadecatrienoate all cia-Δ5,8,11,14-Eicosatetrasenoate 44 52 64 70 75 81 84 -0.5 13 -9 -17 -49 Triglycerides Triglycerides • simples lipids constructed from fatty acids are triglycerides (or triacylglycerol, fats or neutral fats) • triglycerides composed of 3 fatty acids each in ester linkage with a single glycerol • the 3 fatty acids can be of different nature • function of triglycerides – storage of energy – insulation 5 Triglycerides a) H2C CH OO O CC O H2 C O C O b) O (R1) (R2) (R3) C C O C O H2 OC O C H O CH2 Triacylglycerol (triglyceride) c) (R1) (R2) (R3) H H2 H2C C C OH OH OH glycerol Triacylglycerol (triglyceride) Triglycerides in foods • a lot of foods contain triglycerides e.g. vegetable oils, dairy products, animal • vegetable oils contain unsaturated double bonds – liquid form at room temperature – can be changed into margarine(solid form) by catalytic hydrogenation • when lipid-rich foods are exposed to oxygen in air for too long – rancidity: oxidative cleavage of double bond, forming aldehydes and carboxylic acids of shorter chain length => volatile (giving unpleasant smell and taste) 6 Triglycerides as store of energy • in animals, triglycerides are the major form of storage of energy – specialized cells called adipocytes (or fat cells) store most of triglycerides in the form of oily droplets – an obese person can have enough energy storage needs for months • in plants, triglycerides are also stored in seeds as energy storage Triglycerides: storage of energy • advantages of using triglycerides as fuel storage – carbon atoms of fatty acids are more reduced than those of sugars • therefore, oxidation of triglycerides can give more energy – triglycerides are hydrophobic and carries no water • therefore, animals using fat to store energy does not carry extra weight of water of hydration 7 nucleus plasma membrane Fat stores in cells. (a) Crosssection of four guinea pig adipocytes, showing huge fat droplets that virtually fill the cells. Also visible are several capillaries in cross-section. fat (b) Two cambial cells from the underground stem of the plant Isoetes muricata, a wuillwort. In winter, these cells store fats as lipid droplets. Adapted from Principles of Biochemistry (Lehninger) 8 Triglycerides used for other purposes • insulation – warm-blooded polar animals(e.g. seals, penguins) warmcontain a lot of fat under the skin for insulation purposes (white fat) • hibernation – bears accumulates fat reserves before hibernation (brown fat) – also used as energy storage • to match the buoyant density of surrounding water – sperm whale uses the spermaceti organ to store fat – when diving to deep water, fat freezes and has a higher density, thereby matching the high density of surrounding water => buoyant spermaceti Silhouette of a sperm whale, showing the spermaceti organ, a huge enlargement of the snout that lies above the upper jaw. 9 Saponification of triglycerides • ester linkages of triglyceride can be cleaved by either acid or alkali – animal fat + NaOH => glycerol + Na+ salt of fatty acids (soap) • soaps can solubilize or disperse waterinsoluble materials thereby forming micelles • soaps can form aggregates (Ca++ and Mg++ salt of fatty acids) when used with hard water (high content of minerals) and become useless Saponification CH2 CH CH2 O COR1 O COR2 O COR3 Triacylglycerol 3KOH Saponification CH2 CH CH2 OH OH OH K O COR1 + + + + K K O COR2 O COR3 Glycerol Soaps (K+ salt of fatty acids) 10 Wax: energy store & protective coating • ester of – [long chain fatty acid] and – [long chain alcohol] • • wax has higher melting points than triglyceride as energy storage in marine animals like plankton • as water-impermeable coatings – – – vertebrates: hair, skin birds: water-repelling feathers waterplants: shiny leaves for reducing water evaporation Bee’s wax O (a) CH3(CH2)14 C O CH2 (CH2)28 CH3 Palmitic acid 1-Triacontanol (b) (b) (a) Triacontanylpalmitate, the major component of beeswax. It is an ester of palmitic acid with the alcohol triacontanol. (b) A honeycomb, constructed of beeswax, is firm at 25oC and completely impervious to water. The term “wax” originates in the Old English word weax, meaning “the material of the honeycomb.” 11 Structural lipids in membranes • membranes – a double layer of lipids forming a barrier to polar molecules and ions • membrane lipids are amphipathic – being hydrophilic + hydrophobic in the same molecule – hydrophobic: inside; hydrophilic (outside) • 3 types of membrane lipids – glycerophospholipids, sphingolipids and sterols Storage lipids (neutral) Membrane lipids (polar) Phospholipids Glycolipids Triacyglycerols Glycero phospholipids Sphingolipids Sphingosine Fatty acid Sphingosine Fatty acid Glycerol Glycerol Fatty acid Fatty acid Fatty acid PO4 Fatty acid PO4 Fatty acid Alcohol Alcohol Glucose or galactose 12 Glycerophospholipids (phospholipids) • a polar alcohol is linked to C-3 of glycerol through a phosphodiester bond – glycerophospholipids have two parts: • hydrophobic (glycerol and the 2 fatty acids) • hydrophilic (polar head groups of the alcohol and -ve charge of phosphate group) • overall negative charge of glycerophospholipids at physiological pH • diverse glycerophospholipids due to diverse structure of head groups e.g. ethanolamine, choline and inositol • head: polar; tail: (non-polar) (non- O CH2 O O O C CO O P O X Headgroup substituent O Saturated fatty acid (e.g. palmitic) Glycerophospho lipid (general structure) CH CH2 Unsaturated fatty acid (e.g. oleic) Name of X Formula of X Name of glycerophos pholipid Phosphatidic acid Posphatidylethanolamine Phosphatidylcholine Phosphatidylserine Phosphatidyglycerol Phosphatidylinositol Net charge (at pH 7) -1 0 0 -1 -1 -1 --Ethanolamine Choline Serine Glycerol Inositol -H + -CH2-CH2-NH3 + -CH2-CH2-N(CH3)3 + -CH2-CH-NH3 COO-CH2-CH-CH2OH OH OH OH H H H HO OH OH H H - Phosphatidyl glycerol CH2 CHOH O H2 COPOC H2 O HC O CO R1 C O CO R2 H2 cardiolipin -2 13 Sphingolipids • ceramide (sphingosine + fatty acid) + polar head group • 1 polar head group + 2 non-polar tails (sphingosine and fatty acid) • 3 types of sphingolipids (depending on the nature of head group) – sphingomyelins – neutral glycolipids – gangliosides Sphingosine HO CH CH NC=O H OX CH Sphingolipid (general structure) (CH2)12 CH3 Fatty acid Ceramide (when X=H) CH CH2 Name of X Formula of X Name of sphingolipid --Phosphocholine -H O P O CH2 O CH2 + Ceramide Sphingomyelin N(CH3)3 Glucose HH CH2OH O Glucosylcerebroside HO OH H H H OH Di-, tri-, or tetrasaccharide Glc Lactosylceramide Gal Complex oligosaccharide NeuNAc Ganglioside GM2 Glc Gal GalNac Neutral glycolipids 14 Sphingomyelins • phosphocholine or phosphoethanolamine as polar head group • sphingomyelins have overall neutral charge • present in plasma membranes of animal cells particularly myelin sheath (surrounding and insulates axons of myelinated neuron) Neutral glycolipids • sugars as polar head group – sugar connected to OH group of C1 directly (without phosphate group) • sugars – can be D-glucose, D-galactose or N-acetyl-DDDacetylgalactosamine – one to six sugar units can be present • present largely in outer side of plasma membrane • e.g. glucosylcerebroside (single glucose as head group) – present in plasma membrane of non-neural tissues non- 15 Gangliosides • the most complex sphingolipids • complex head groups containing several sugar units with one or more terminal sugar units being N-acetylneuramic acid (sialic acid) – overall negative charge at pH=7 • mainly present in membrane lipids in gray matter of human brain Sphingolipids: sites of biological recognition • ABO blood groups of human is determined by the cell surface glycosphingolipids – blood group antigen A or B or O depends on the terminating sugar residues of the glycosphingolipids on the cell surface – all 3 blood groups have the same basic structure: GlcGlcGal-GalNAc Gal– but at the terminal, the 3 blood groups differ: • O: Fucose • A: Fucose and GalNAc • B: Fucose and Gal 16 Ceramide Sphingosine Fatty acid O Antigen G lc G al G a lN A c G al Fuc A Antigen G lc G al G a lN A c G al G a lN A c Fuc B Antigen G al G al G lc G a lN A c G al Fuc Tay-Sachs disease • genetically defective of an enzyme (hexosaminidase A) which normally cleaves the N-acetylgalacto- samine and D-galactose residue in the polar head group of a ganglioside – resulting in the accumulation of intermediates • specific ganglioside intermediates accumulates in brain and spleen and causes degeneration of nervous system – symptoms: mental retardation • diagnosis: hexosaminidase A activity 17 Lipids with specific biological activities • structural lipids plays a “passive” role in a cell – – – storage lipids (made up of 50% of adipocytes) wax membrane lipids (5- 50 % of cells) (5- • other lipids, although at a lower amount compared to structural lipid, plays a more “active” role – – – – steroid hormone intracellular signaling cofactors of enzymes electron carriers Sterols • • • present in plasma membrane of eukaryotic cells consists of 4 fused rings and structure is almost planar and rigid Amphipathic – Polar: OH group – Non-polar: fused rings Non- • OH group at C3 usually condenses with a fatty acid to form a sterol ester for storage and transport 18 Sterols CH3 HC CH3 CH3 OH CH3 CH3 C O N CH2 H CH2 SO3- Alkyl CH2 side CH 2 chain CH2 HC CH3 CH3 HO OH Taurocholic acid (a bile acid) Polar head group HO CH3 C D Steroid nucleus A B Sterols • cholesterol being the major sterol in animal tissues – cholesterol present in membrane and blood – cholesterol makes membrane more “fluid” – high blood cholesterol is associated with a high risk of heart diseases • sterols being the precursor of bile acid – functions as detergents in intestine to emulsify dietary fat to make them accessible to digestive lipases 19 Steroid hormones • hormones – produced in one tissue and carried in bloodstream and functions in another tissue – works in extremely low concentration (10-9 M) • all steroid hormones have the structure of a steroid like that of cholesterol – male and female sex hormone – hormones from adrenal cortex • cortisol: glucose metabolism • aldosterone: for salt excretion OH CH3 CH3 Testosterone OH CH3 Estradiol O HO CH2OH C HO CH3 Cortisol CH3 H O C HO CH3 CH2OH C O O OH O O Aldosterone 20 Intracellular signaling • certain plasma membrane phospholipids (e.g. phosphatidylinositol-4,5-bisphosphate) can be cleaved , upon hormone stimulation, to release the head group (Inositol 1,4,5-triphosphate), leaving the remaining part (1,2-diacylglycerol) on the plasma membrane – intracellular inositol 1,4,5-triphosphate can then 1,4,5activate the release of Ca++ from endoplasmic reticulum – diacylglycerol can then migrate on the lipid bilayer to activate protein kinase C (on membrane) to add a phosphate group to another protein (either inactivating or activating this protein) Exterior Phospholipase C fatty acids Plasma membrane CO O CH2 O CO CO H2O CO O C CH2OH H O CH2 C CH2 O H OPO O OH 1,2.Diacylglycerol (DAG) OPO 23 PO 23 Phosphatidylinositol 4,5-bisphosphate (PIP2) OHHO 2OPO 3 OPO 23 O OH OH HO OPO3 2- Cytosol Inositol 1,4,5-trisphosphate (IP3) 21 Hormone Exterior Receptor Phosphatidyl inositol 4,5bisphosphate ~~~ ~~~ 1,2-Diacyglycerol ~~~ ~~~ Protein kinase C Activation Cytosol Protein (inactive) Protein- P (active) G protein Phospholipase C IP3 Activation ER Ca2+ channel sensitive to IP3 Ca2+ Cellular response Ca2+ Endoplasmic reticulum Eicosanoids are potent biological effectors • eicosanoids (eikosi-: 20 carbons) are fatty acid derivatives that function like hormones – unlike hormones, they work on local tissues only • eicosanoids are all derived from a 20carbon polyunsaturated fatty acid arachidonic acid • three main biological eicosanoids – prostaglandins – thromboxanes – leukotrienes 22 O Membrane phospholipid CH CH2 O O C 5 CO 8 CH2 Polar head group O X 14 11 Phospholipase A2 8 5 1 COOH Arachidonic CH3 acid 11 14 O 8 CO2CH3 OH Prostaglandin E1 (PGE1) 8 O O 12 CO2CH3 OH Thromboxane A2 O CH3 Leukotriene A4 CO2- 12 OH Prostaglandins (PG) • all contain a 5-membered ring e.g. PGE1, PGE2 etc • first discovered in prostate gland (prostaglandins) • prostaglandins act in many tissues by regulating the synthesis of an intracellular signaling molecule, cyclic AMP • diverse functions including – induce smooth muscle contraction during labor – regulate blood flow to specific organs – elevate body temperature and causes inflammation , resulting in pain • aspirins reduce pain by inhibiting formation of prostaglandins 23 Thromboxanes • contain a 6-member ring containing an oxygen (-ox-) • first isolated from blood platelets or thrombocytes (thrombo-) • produced by platelets during formation of blood clot • function: – vasoconstriction- reducing blood flow to wound Leukotrienes • • • first found in leukocytes (leuko-) contain three conjugated double bonds (-triene) functions: – induce muscle contraction lining airways to lung • overproduction of leukotrienes results in asthma • allergic reactions to bee stings or penicillins also result in contraction of the smooth muscle of the lung – can be fatal 24 Fat-soluble vitamins: A,D,E,K • Vitamin A: All- trans Retinol AllRetinol a pigment (11-cis retinal) essential for vision (11deficiency: dry skin, dry eyes, retarded development/growth, night blindness – source: fish liver oils – not present in plant, but β-carotene from carrots can be enzymatically converted to vitamin A by most animals – Recommended Daily Allowance (RDA) – – – • 800-100 μg (USA standard !!!) 800- H3C CH3 CH3 11 12 H3C CH3 CH3 11 12 CH3 O H CH3 H3C O H CH3 11-cis-retinal All-trans-retinal H3C CH3 CH3 11 12 CH3 CH2OH CH3 All-trans-retinol (Vitamin A) 25 Vitamin A biochemistry & vision • Light ( a photon) is absorbed to stimulate a photoreceptor cell (e.g. retinal rod cells) • Retinal rod cells contain may discs with the light-sensitive molecule: rhodopsin • Rhodopsin – 11-cis-retinal (a prosthetic group) + opsin (a protein) H3C CH3 CH3 11 12 CH3 H3C O H + H2N--(CH2)4--Opsin (ε NH2 group of lysine of opsin) 11-cis-retinal - H2O CH3 CH3 H3C 11 12 H CH3 H3C * Rhodopsin (11-cis-retinal joined to opsin via a Schiff Base) N--(CH2)4--Opsin + * Schiff Base 26 Model of rhodopsin • 7-helix transmembrane receptor • 11-cis retinal located near center of bilayer • 2 N-glycosylations • Phosphorylation of serines Or threonines deactivates photoexcited rhodopsin 27 Schiff base 11-cis retinal Opsin Rhodopsin All-trans retinal Hydrolysis of Schiff base Opsin Photoactivated Rhodopsin Opsin 11-cis retinal Oxidation All-trans retinal All-trans retinol Reduction All-trans retinal Diffuse away 28 ...
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