2013 W. H. Freeman and Company. 10 Lipids

Transcription

1 2013 W. H. Freeman and Company 10 Lipids

2 Storage lipids: TG lipid 의기능 : 1 Energy source 3 Electrical insulator 2 Thermal insulator 4 Membrane 의구성성분, 방수, 부력, cofactor, signaling 등 지방대사이상 : obesity, atherosclerosis, metabolic syndrome 1) 지방산 (fatty acid, FA) 의종류 1 지방산 : carboxylic acid 탄화수소사슬 : Hydrophobic + Hydrophilic 2 필수지방산 a) Linoleic acid 18:2( 9,12 ) 식용유, ω 6 FA b) -Linolenic acid 18:3( 9,12,15 ) 들깨, ω 3 FA c) Arachidonic acid 20:4( 5,8,11,14 ), ω 6 FA 3 Eicosapentaenoic acid(epa) 20:5( 5,8,11,14,17 ), DHA 등푸른생선 ω 3 FA 4 Oleic acid 18:1( 9 ) 올리브유, ω 9 FA CH 3 -CH 2 COOH -terminus c-terminus ( 1 ) ( 1, n-1)

3 Lipids: Structurally Diverse Class Organic molecules that are characterized by low solubility in water, that is, are relatively hydrophobic.

4 Biological Functions of Lipids Storage of energy Reduced compounds: lots of available energy Hydrophobic nature: good packing Insulation from environment Low thermal conductivity High heat capacity (can absorb heat) Mechanical protection (can absorb shocks) Water repellant Hydrophobic nature: keeps surface of the organism dry Prevents excessive wetting (birds) Prevents loss of water via evaporation Buoyancy control and acoustics in marine mammals Increased density while diving deep helps sinking (just a hypothesis) Spermaceti organ may focus sound energy: sound stun gun?

5 More Functions Membrane structure Main structure of cell membranes Cofactors for enzymes Vitamin K: blood clot formation Coenzyme Q: ATP synthesis in mitochondria Signaling molecules Paracrine hormones (act locally) Steroid hormones (act body-wide) Growth factors Vitamins A and D (hormone precursors) Pigments Color of tomatoes, carrots, pumpkins, some birds Antioxidants Vitamin E

6 Classification of Lipids Based on the structure and function Lipids that do not contain fatty acids: cholesterol, terpenes, Lipids that contain fatty acids (complex lipids) can be further separated into: storage lipids and membrane lipids

7 Fatty Acids Carboxylic acids with hydrocarbon chains containing between 4 to 36 carbons Almost all natural fatty acids have an even number of carbons Most natural fatty acids are unbranched Saturated: no double bonds between carbons in the chain Monounsaturated: one double bond between carbons in the alkyl chain Polyunsaturated: more than one double bond in the alkyl chain

8 Fatty Acid Nomenclature Omega-3 fatty acids are essential nutrients Humans need them but cannot synthesize them Including ALA, DHA, and EPA Although DHA and EPA can be synthesized from ALA (oleic acid)

9 권장섭취 : Omega 6 FA:3 FA=1:1~4:1 >>> 에스키모인, 지중해식단북미인 : Omega 6 FA:3 FA=10:1~30~:1: >>> 심장병, 뇌졸중다발

10 Fatty Acid Nomenclature Palm oil Olive oil ( 올리브유 ) Flaxeed oil ( 아마씨유 ) Perilla oil( 들깨유 ) Soybean oil( 식용유 )

11 Lipid peroxidation MDA

12 Solubility and Melting Point of Fatty Acids Solubility decreases as the chain length increases Melting Point decreases as the chain length decreases decreases as the number of double bonds increases

13 Conformation of Fatty Acids The saturated chain tends to adopt extended conformations The double bonds in natural unsaturated fatty acids are commonly in cis configuration, which kinks the chain

14 Melting Point and Double Bonds Saturated fatty acids pack in a fairly orderly way extensive favorable interactions Unsaturated cis fatty acid pack less orderly due to the kink less-extensive favorable interactions It takes less thermal energy to disrupt disordered packing of unsaturated fatty acids: unsaturated cis fatty acids have a lower melting point

15 Trans Fatty Acids Trans fatty acids form by partial dehydrogenation of unsaturated fatty acids Done to increase shelf life or stability at high temperature of oils used in cooking (especially deep frying) A trans double bond allows a given fatty acid to adopt an extended conformation Trans fatty acids can pack more regularly and show higher melting points than cis forms Consuming trans fats increases risk of cardiovascular disease Avoid deep-frying partially hydrogenated vegetable oils Current trend: reduce trans fats in foods (Wendy s, KFC)

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19 Triacylglycerols (Nonpolar) Majority of fatty acids in biological systems are found in the form of triacylglycerols Solid ones are called fats Liquid ones are called oils The primary storage form of lipids (body fat) Less soluble in water than fatty acids due to the lack of charged carboxylate group Less dense than water: fats and oils float

20 Triacylglycerols

21 Fats Provide Efficient Fuel Storage The advantage of fats over polysaccharides: Fatty acids carry more energy per carbon because they are more reduced Fatty acids carry less water per gram because they are nonpolar Glucose and glycogen are for short-term energy needs, quick delivery Fats are for long-term (months) energy needs, good storage, slow delivery

22 Fats Provide Efficient Fuel Storage

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24 Waxes Waxes are esters of long-chain saturated and unsaturated fatty acids with long-chain alcohols Insoluble and have high melting points Variety of functions: Storage of metabolic fuel in plankton Protection and pliability for hair and skin in vertebrates Waterproofing of feathers in birds Protection from evaporation in tropical plants and ivy Used by people in lotions, ointments, and polishes

25 Structural Lipids in Membranes (Polar) Contain polar head groups and nonpolar tails (usually attached fatty acids) Diversification can come from: modifying a different backbone changing the fatty acids modifying the head groups The properties of head groups determine the surface properties of membranes Different organisms have different membrane lipid head group compositions Different tissues have different membrane lipid head group compositions

26 Structural lipids in membranes 1. Glycerophospholipid 1) 구조 glycerol 에결합되어있는 2 개의지방산이소수성부위를형성 1 머리부분의극성종류에따라명명 2 O CH 2 -O-C- O CH 2 -O-C- O CH 2 -O-P-O- O : C 16 /C 18 인포화지방산 : C 18 /C 20 인불포화지방산 2) Ether Lipid 염증, allergy 관련 1 plasmalogen ether 결합된핚개의 alkenyl chain : 심장인산지방질의 1/2 2 platelet-activating factor(paf) glycerol 의 1 C 위치에 ether 결합된긴 alkyl chain : 호염기구 basophil 에서분비되어 2 C 위치에 carboxyl 기가 ester 결합 혈소판의응집 & 혈소판으로부터 serotonin 의분비를촉짂시키는강력핚물질

27 2. Sphingolipid 1) 구조 1 Sphingosine이나그유도체 1분자 + 사슬지방산 1분자 + glycoside 결합 / phosphodiester 결합 2 glycerophospholipid와다른점 : glycerol 포함ⅹ 3 OH-CHCH=CH-(CH 2 ) 12 -CH 3 2) 종류 CH-NH-C : ( 지방산 ) ceramide CH 2 -O-X O 1 ceramide (H=X): 모든 sphingolipid의기본구조 2 sphingomyelin (X=phosphocholine): sphingolipid cell membrane, myelin sheath 3 Glucosylcerebroside 4 globoside 5 ganglioside * N-acetylneuraminic acid (sialic acid) 3) 역핛 : 싞경세포의원형질막, 세포표면에서 recognition site 로작용

28 Some common types of storage and membrane lipids

29 Glycerophospholipids Primary constituents of cell membranes Two fatty acids form ester linkages with the first and second hydroxyl groups of L-glycerol-3-phosphate Head group is charged at physiological ph

30 General Structure of Glycerophospholipids Unsaturated fatty acids are commonly found connected to C2 The highly polar phosphate group may be further esterified by an alcohol; such substituent groups are called the head groups

31 Examples of Glycerophospholipids Mt 에多

32 Phosphatidylcholine Phosphatidylcholine is the major component of most eukaryotic cell membranes Many prokaryotes, including E. coli, cannot synthesize this lipid; their membranes do not contain phosphatidylcholine

33 Ether Lipids: Plasmalogen Vinyl ether analog of phosphatidylethanolamine Common in vertebrate heart tissue Also found in some protozoa and anaerobic bacteria Function is not well understood Resistant to cleavage by common lipases but cleaved by few specific lipases Increase membrane rigidity? Sources of signaling lipids? May be antioxidants?

34 Ether Lipids: Plasmalogen

35 Ether Lipids: Platelets-Activating Factor Aliphatic ether analog of phosphatidylcholine Acetic acid has esterified position C2 First signaling lipid to be identified Stimulates aggregation of blood platelets Plays role in mediation of inflammation

36 Sphingolipids The backbone of sphingolipids is NOT glycerol The backbone of sphingolipids is a long-chain amino alcohol sphingosine A fatty acid is joined to sphingosine via an amide linkage rather than an ester linkage as usually seen in lipids A polar head group is connected to sphingosine by a glycosidic or phosphodiester linkage The sugar-containing glycosphingolipids are found largely in the outer face of plasma membranes

37 Sphingolipids

38 Sphingomyelin Ceramide (sphingosine + amide-linked fatty acid) + phosphocholine attached to the alcohol Sphingomyelin is abundant in myelin sheath that surrounds some nerve cells in animals

39 Sphingomyelin is structurally similar to phosphatidylcholine

40 Glycosphingolipids and Blood Groups The blood groups are determined in part by the type of sugars located on the head groups in glycosphingolipids. The structure of sugar is determined by an expression of specific glycosyltransferases Individuals with no active glycosyltransferase will have the O antigen Individuals with a glycosyltransferase that transfers an N- acetylgalactosamine group have A blood group Individuals with a glycosyltransferase that transfers a galactose group have B blood group

41 Glycosphingolipids determine blood groups acetylgalactosamine galactose

42 glycosyltransferases :A 전이효소 B: 전이효소로변환 A: 전이효소상실

43 Membrane lipid 의이상축적에의해유발되는유전질환 1 원인 : ribosome 내가수분해효소들에의핚 sphingolipid 의가수분해에이상 이있어중갂분해산물들이조직에축적되어질환야기 2 종류 sphingomyelinase( 결함 ) ⅰ) Sphingomyelin ceramide : Niemann-Pick disease 뇌, spleen, 갂장에 sphingomyelin 축적 ⅱ) Ceramide GM2 hexosaminidase A( 결핍 ) ceramide GM3 3 혈액형결정 : Tay-Sachs disease 뇌, spleen 에 ganglioside GM2 축적 : Glycosphingolipid (ceramide 의 1 C -OH) 의머리부분에붙은당의종류에따라 O, A, B 형결정됨 3) 가수분해 : phospholipase A 1, A 2, phospholipase C, D

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45 Defects in the turnover of membrane lipids lead to a number of diseases

46 Sterols and Cholesterol Sterol Steroid nucleus: four fused rings Hydroxyl group (polar head) in the A-ring Various nonpolar side chains The steroid nucleus is almost planar

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48 Physiological Role of Sterols Cholesterol and related sterols are present in the membranes of most eukaryotic cells Modulate fluidity and permeability Thicken the plasma membrane Most bacteria lack sterols Mammals obtain cholesterol from food or synthesize it de novo in the liver Cholesterol, bound to proteins, is transported to tissues via blood vessels Cholesterol in low-density lipoproteins tends to deposit and clog arteries Many hormones are derivatives of sterols

49 Steroid Hormones Steroids are oxidized derivatives of sterols Steroids have the sterol nucleus, but lack the alkyl chain found in cholesterol More polar than cholesterol Steroid hormones are synthesized from cholesterol in gonads and adrenal glands They are carried through the body in the bloodstream, usually attached to carrier proteins Many of the steroid hormones are male and female sex hormones

50 Steroid Hormones

51 Biologically Active Lipids Are present in much smaller amounts than storage or structural lipids Play vital roles as signaling molecules between nearby cells Lipid soluble vitamins (A, D, E, and K)

52 5) Eicosanoid 1 Arachidonic acid 20:4( 5,8,11,14 ) 에서유래됨 2 역핛 : 방분비 (paracrine, tissue) H. 생성된지점주위의인귺세포들에만작용을나타내는물질 3 종류 a) Prostaglandin 종류 : PGE(ether 에녹음 ), PGF( 인산완충액에녹음 ), etc 작용 : camp 의합성조절 세포 / 조직의기능에세포내 messenger 로서영향 ⅰ) 자궁평활귺수축유발 ⅱ) 혈류의흐름, 각성 - 수면 cycle, hormone 에대핚조직의반응에영향 ⅲ) 발열염증반응, 통증유발 b)thromboxane 구조 : 6 원환 ether 구조, 혈소판에서생성 역핛 : 혈액응고가생성된부위로혈액의흐름을감소시킴 NSAID( 항염증약물 ): arachidonic acid PGs, Thromboxane(TX) PGH 2 synthase (COX-1,2) 억제 ex) aspirin, ibuprofen, etc.

53 c) Leukotriene 구조 : =-=-=-, 백혈구에서발견특징 : 강력핚생물학적 messenger ex) LTD 4 : 기도평활귺수축유발 cf) COX-1: 일정발현, PGE 2 생성으로위점막보호 / 소염, 짂통제 : 위장장애유발 EPA 2H Eicosapentaenoate(EPA) PGD 3, PGI 3 PGE 3, TXA 3 혈관수축 ⅹ, 혈소판응집 ⅹ PGF 3 Diet LTA 5 LTB 5 ω 3 FA 섭취하면? LTC 5 6) Steroid H 7) Vt A, D TXA 3, PGE 3, PGI 3 생성 ω 6 지방산의생성물인 TXA 2 ( 혈관수축, 혈소판응집 ), PGE 2 PGI 2 생성억제 혈관질환예방

54 Phospholipids Glucocorticoids 一 PhospholipaseA 1 Inhibit induction Arachidonate 一 5-lipoxygenase inhibitors Cyclooxygenase 1 and 2 一 COX/LOX inhibitors 一 5-lipoxygenase Cyclic endoperoxides 5-HPETE PGI 2 vasodilator, hyperalgetic, inhibits platelet aggregation TXA 2 stimulate platelet aggregation, vasoconstrictor LTA 4 LTB 4 (chemotaxin) PGF 2α broncoconstrictor, myocardial contraction PGD 2 inhibits platelet aggregation, vasodilator PGE 2 Vasodilator, hyperalgetic LTC 4 LTD 4 LTE 4 Bronchoconstrictors, Increase vascular permeability

55 Arachidonic Acid Derivatives as Signaling Lipids Enzymatic oxidation of arachidonic acid yields Prostaglandins (inflammation and fever) Thromboxanes (formation of blood clots) Leukotrienes (smooth muscle contraction in lungs)

56 Vitamin D regulates calcium uptake

57 Vitamin A (Retinol) Involved in visual pigment Precursor for other hormones involved in signaling

58 Vitamin E, K, and other lipid quinones are antioxidants

59 Lipids can provide pigment

60 Polyketides are biologically active lipids with medicinal uses

61 Lipidomics

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63 Chapter 10: Summary In this chapter, we learned: lipids are a structurally and functionally diverse class of molecules that are poorly soluble in water triacylglycerols are the main storage lipids phospholipids are the main constituents of membranes sphingolipids play roles in cell recognition cholesterol is both a membrane lipid and the precursor for steroid hormones some lipids carry signals from cell to cell and from tissue to tissue