《功能性脂类》PPT课件

1、PUFA,Arachidonic Acid (AA),Source,Animal Plant Human 40%50% of brain and nerve PUFA plasm 400mg/L milk from mother 0.4% Microorganism Hyphochytrimycete Hytridiomycetes Oomycetes Mortierella,AA is the precursors of Eicosanoids: Prostaglandins and leukotrienes are locally acting, hormone-like lipids d

2、erived from dietarily essential unsaturated fatty acids that are important drug targets Actions of prostaglandins include: inflammatory, pain/fever, blood clotting (via control of platelet-endothelial cell interactions), intestinal, renal, uterine effects Actions of leukotrienes include: mainly hype

3、rsensitivity and allergic reactions,Synthesis of Eicosanoids,R= H or CH3,In cell membrane,Hydrolysis of sn-2 ester bond by phospholipase A2 (PLA2) or C,Arachidonate,Liberation of arachidonic acid and its metabolism to prostaglandins/ thromboxanes or to leukotrienes,Synthesis of Prostaglandin,Cyclic

4、endoperoxide,Hydroperoxide,Prostaglandin endoperoxide synthetase,(COX-1),COX-2,Hydroperoxidase,Prostaglandin endoperoxide synthetase (also called cyclooxygenase) possesses both cyclooxygenase and hydroperoxidase activity Two forms of cyclooxygenase: COX -1 - constitutively expressed COX -2 - inducib

5、le,PGH2,PGG2,PGH2 central intermediate (Head of pathway),PGF2 labor induction (Fetus),Conversion of PGH2 to prostaglandins and thromboxane of the “2-series”,TXB2 inactive,Non-Enzymatic,Leukotriene Biosynthesis,Arachidonic acid,5-Hydroperoxyeicosa- 6,8,11,14-tetraenoic acid (5-HPETE),5-Lipoxygenase,L

6、eukotriene A4 (LTA4),5-Lipoxygenase,Glutathione LTC4 synthase,Leukotriene C4 (LTC4),Leukotriene E4 (LTE4),- Glu - Gly,LTA Hydrolase,Leukotriene B4 (LTB4),Leukotrienes are important mediators of inflammation,Cysteinyl leukotrienes,Leukotriene Biosynthesis (Contd),Arachidonic acid,12-Lipoxygenase,12-H

7、ydroperoxyeicosa- 5,8,10,14-tetraenoic acid (12-HPETE),12-Hydroxyeicosa- 5,8,10,14-tetraenoic acid (12-HETE),Leukotriene Receptor,Accolate,Anti-inflammatory glucocorticoids inhibit phospholipase A2 and, therefore, prevent both prostaglandin and leukotriene formation Nonsteroidal anti-inflammatory dr

8、ugs (NSAIDs) inhibit cyclooxygenase (COX), and thus prevent only prostaglandin/thromboxane synthesis Zyflo inhibits lipoxygenase to preclude only leukotriene synthesis; Accolate is a selective leukotriene receptor antagonist (blocker),Cyclooxygenase (COX) Inhibitors,Nonsteroidal antiinflammatory dru

9、gs:,Acetylsalicylic acid (aspirin),Ser-530,Irreversible inhibition of COX by acetylation of the active site,Actions of Aspirin: Antiinflammatory (COX-2 inhibition) GI injury (COX-1 inhibition),COX-2 Selective Inhibitors,Rofecoxib (Vioxx),Celecoxib (Celebrex),Glucocorticoids block COX-2 expression,Le

10、ukotriene Biosynthesis Inhibition,Zileuton (Zyflo) An inhibitor of 5-lipoxygenase Used in the treatment of asthma,Function of Prostaglandins,TXA2 platelets aggregation vasoconstriction PGI2 endothelial cells platelet disaggregation vasodilation gastric mucosa decreased stomach acid PGE2 many cells w

11、aking pain inflammation fever renal arteriolar dilation,Function of Prostaglandins,PGD2 mast cells, fat cells sleep precursor to PGJ2 PGF2 labor inducing PGJ2 fat cells from PGD2 induces fat cell differentiation,Biological activities of leukotrienes,LTB4- potent chemoattractent - mediator of hyperal

12、gesia - growth factor for keratinocytes LTC4- constricts lung smooth muscle - promotes capillary leakage 1000 X histamine LTD4- constricts smooth muscle - lung airway hyperactivity - vasoconstriction LTE4- 1000 x less potent than LTD4 (except in asthmatics),Function of AA,Second signal Improve cAMP,

13、 cGMP Immunity HETEs, HPETEs, LT inhibit immune cell LTB4, LTD4, LTE4 inhibit immunity Cardiovascular Disease,Liver and Gallbladder Inflammation Nerve Cell Division,Application,Nannie, Pregnant, Baby FAO/WHO baby recipe milk powder AA 60mg/kg DHA 40mg/kg,Application,Improve remember and eyesight Adj

14、ust blood TG and Sugar Prevent CVD Anti-tumor Cometic Other,Animal experiment results,AA的产业化技术路线,工业化生产,菌体,提油,菌体胶囊,干菌体,油胶囊,功能保健品,纯化油,食品添加剂,高级饲料,前列腺素,科 研,新 药,-FA,Zhang Dequan,-3 PUFA,18:2 Linoleic acid(LA) 18:3 -Linolenic acid(GLA) 20:3 Dihomo-linolenic acid 20:4 Arachidonic acid(AA) 22:4 Adrenic acid

15、,18:3 -Linolenic acid(LNA) 20:5 Eicosapentaenoic acid (EPA) 22:5 Docosapentaenoic acid(DPA) 22:6 Docosahexaenoic acid (DHA),-6 PUFA,KINDS,-6 and -3 synthesize,-6 LA GLA AA -6 eicosanoids,-3 LNA EPA DHA -3 eicosanoids,Eicosanoids synthesis,AA,PGH2,The eicosanoids and their biosynthetic origins. A) Sy

16、nthesis from -6 precursors,LA(6),PGI2,PGE2,PGD2,PGF2,TXA2,TXB2,LTs,A.,The eicosanoids and their biosynthetic origins. B) Synthesis from -3 precursors,B.,-Linolenic Acid (3 essential fatty acid) for membrane integrity in phospholipids,Diet -3 fatty acids,Eicosapentaenoic Acid EPA (3) for membrane int

17、egrity in phospholipids,plant sources,Docosahexaenoic Acid DHA (3) in breast milk; required for infant brain development,-FA also leads to production of PGI3 and TXA3 PGI3 production is favored, and it also has much greater intrinsic activity (than its TXA3 counter-hormone) to favor vasodilation and

18、 platelet disaggregation with a reduced risk of thrombosis (blood clotting). This explains why -3 dietary fatty acids prevent vascular disease and heart attacks,Control of platelet aggregation. Suppression of platelet aggregation by drug or dietary intervention,-6 promote TXA2 synthesizing -3 promot

19、e TXA3 synthesizing,FUNCTION Anticancer,CVD,-6 promote PGE2 synthesizing -3 inhibit PGE2 synthesizing -3 inhibit platelet aggregation and blood to clot by promoting formation TXA3, PGI3 modify dyslipidemia EPA/DHA inhibit VLDL and apoB, by lower triacylglycerols and Cholesterol, increase in HDL2-C,i

20、mprove arterial function, inhibit monocytes migratinon into plaque, and cytkine, PDGF and its mRNA production, relax blood vessels and reduce BP by stimulate endothelial production of NO anti arrhythmias by altering cell membrane fatty acids composition and electrophysiological function, reduce vuln

21、erability to ventricular fibrillation, and less risk of cardiac arrest & sudden death anti-inflammation by reducing production of TXB2, PGE2,-6 Decreased Chol & LDL C Small reduction HDL Small reduction TGs Lower serum cholesterol Increased thromboxane A2 Increased prostacylin 12 Control of inflamma

22、tion Platelet aggregation Vasoconstriction/dilation Membrane structure - fluidity, receptors, enzymes and channels,-3 Decreased Chol & TG Little effect on LDL Decreased thromboxane A2 Increased prostacylin 12 Antithrombotic effect Reduce platelet aggregation Preventing cardiac arrest Decreasing risk

23、 of breast and colon cancer Both omega 3 and 6 FA improve blood pressure, Omega 3 FA has a greater effect than omega 6 FA,LNA,Structure,-Linolenic ALA 18:3 cis9,12,15 - Linolenic GLA 18:3 cis 6,9,12,ALA GLA EPA Dihomo-GLA DHA AA,ALA,Perilla oil 45% 50% oil，ALA 60% Linseed oil 35% oil，ALA 50%,GLA,Eve

24、ning Primrose 23%30% oil, GLA 8%10%,CONJUGATED LINOLEIC ACID CLA,STRUCTURE,trans 10, cis 12 CLA cis 9, trans 11 CLA linoleic acid,HISTORY,1951. Nichols synthesize CLA. 1966,.Kepler discover that 9c,11t-CLA is the mediators of hydrogenation of linoleic in ruminant. 1978, Michael Pariza dicover CLA ca

25、n anticancer. 1985, Pariza, CLA inhibit mouse skin cancer. 1991，Ha et al, CLA inhibit BP induced tumor. 1994, Ip, CLA inhibit mouse galactophore cancer. 1990s, the evidence of CLA anti-tumor. 1997, Pariza, CLA decrease fat mass, increase LBM. 1999, Japan, built CLA plant，CLA capsule of decreasing fa

26、t come into market in USA. 2002, China, CLA “Tenth five Plan”. 2003, CLA product will come into market,Body Composition,Increased lean body mass (LBM) and decreased fat mass(FM) 提高肉毒碱棕榈酰转移酶（一种脂肪-氧化的限速酶） 提高荷尔蒙敏感酶（负责脂肪水解释放至血液中的酶） inhibit 脂蛋白脂肪酶 （促进脂肪吸收） Increase 3T3-L1脂肪细胞中的脂肪水解速度,Body Composition,Exa

27、mple 2000,Blankson, 1.7-6.8g CLA /d FM decreased obviously LBM decreased obviously 2001, Riserus, et.al, 4.2g CLA /d FM decreased obviously 2001, Smedman, , et al. 4.2g CLA /d FM decreased obviously,Body Composition, 2001, Mougios, 3g/dCLA, 90d 20%less FM 5%more LBM 2001, Smedman, et al, Mice diets

28、containing 0.5% CLA 60% less FM 10% more LBM 2002, Riserus, et al.3.4g CLA/d FM decreased obviously,Body Composition, 2003, Susie, et al. 60 subjects 5 groups 12 capsules/day Placebo = olive oil Treatment Groups CLA Doses g/d: 1.7 3.4 5.1 6.8,Body Composition,Changes from Weeks 0 to 12 1.7 3.4 5.1 6

29、.8 9 Weight, kg -0.4 -0.4-0.1-0.8+1.4 BFM, kg-1.2*-1.7*-0.4-1.3*+1.5 LBM, kg 0.9 1.3 0.5 0.9* -0.05,*Significant changes from placebo (p 0.05) *Significant changes within groups ( 0.05),Daily Dosage of CLA,Placebo,g/d,Body Composition, 2003, Susie, et al. 6 men, 3 g CLA /day, 6 weeks,CLA Possible Me

30、chanism,Bloodstream,Muscle,Triglyceride,FFA,Adipocytes,LPL,Step 1: CLA decreases the activity of adipocyte LPL,Step 2: CLA increases the activity of Hormone Sensitive Lipase within the adipocyte increasing lipolysis,CLA - Potential Mechanism,Bloodstream,Muscle,FFA,TG,B-Oxid,CO2,Energy,TG,TG,Prevent

31、Cancer,动物实验证明：CLA对胃癌、皮肤癌、前列腺癌有明显的抑制作用。 细胞培养实验也证明，CLA能抑制人乳腺癌、肠癌、肺癌、黑色素癌、白血病、间皮瘤、皮胶质细胞癌、卵巢癌、结肠癌、前列腺癌和肝癌等细胞株的生长和增殖。实验同时也发现，植物油中普遍存在的亚油酸对癌细胞的增殖具有促进作用。,Prevent Cancer,CLA is a potent anticancer Direct influence Decrease fat Improve cachexia,Prevent Cancer,Prevent Cancer,Increase of 55mg/d of CLA reduce t

32、he risk of breast cancer “If margarine was replaced by butter in the American diet it would increase CLA intake by approximately 54mg/day.”,Prevent CVD,CLA能够降低LDL与HDL的比例 能够抑制由花生四烯酸或胶原质引起的血小板聚集，阻止脂肪和血小板在粥样病变的动脉壁上的沉积，从而抗血栓。,Prevent CVD,Rabbits were fed 0.5 g CLA per day Lower circulating LDL Lower tri

33、glyceride concentrations Less atherosclerosis,CLA Impact on TC,CLA: Impact on HDLc,CLA: Impact on LDL,CLA: Impact on TG,Prevent diabetes,CLA can adjust and decrease blood glucose, prevent diabetes.,Prevent diabetes Plasma Glucose,Decrease blood pressure,CLA具有扩张和松弛血管平滑肌、抑制血液运动中枢的作用，降低了血液循环的外周阻力，使血压下降

34、，尤其是使舒张压下降更为明显。,Promote growth,CLA能够提高体内维生素A的水平，并被认为可能是重要的生长因子。动物实验证明：补充了CLA的个体，对食物的吸收效率更高，生长发育更快。用添加了CLA的食物喂养怀孕期的老鼠，能使其生出的小鼠比一般的小鼠长得更快；断奶后，持续补充CLA的小老鼠能保持自己的生长优势。,Anti-oxidation,CLA是一种强有力的抗氧化剂。研究人员在比较CLA与其它抗氧化剂时发现，在磷酸盐缓冲液/乙醇溶液中CLA可以抑制不饱和脂肪酸的过氧化，其效果与丁基羟基甲苯(BHT)相近，而优于维生素E。,Improve bone metabolism,CLA能

35、够促进骨组织的分裂与再生，促进软骨细胞的合成及矿物质在骨组织中的沉积，对骨质健康有积极作用。,Increase immunity,研究证明，CLA能够促进细胞分裂，阻止肌肉退化，延缓机体免疫机能衰退，减少有脂多糖诱导的炎症反应。上述结果表明，CLA能提高动物免疫系统功能，增强仔猪的抗病能力。,Source,Naturally occurring fatty acid found in ruminants, meat + dairy products Product of normal fermentation in the rumen Processed now from safflower

36、oil Greater than 90% of the cis-9, trans-11 CLA secreted in the milk of grazing cows is produced in the mammary gland from endogenous conversion of trans-11 18:1 via 9-desaturase (Figure 1). Trans-11 18:1 is an intermediate formed during biohydrogenation of linoleic and linolenic acids. Increasing t

37、he concentration of CLA in milk should be possible if the mammary supply of trans-11 18:1 is increased.,Source,Intake quantity,3g/70kg,TRANS FATTY ACIDS TFAs,Trans Fatty Acid,Saturated Fatty Acid,Cis Fatty Acid,Structure,Cis-9-octadecenoic acid Trans-9-octadecenoic acid (Oleic acid) (Elaidic acid),D

38、rawing by S,Structure,History,1990, Rondld Mensink, TFA increase LDLc, dcrease HDLc. 1994, Institute of Shortenings& Edible Oils similar report. 1994, Joseph Judd (Research Center of Human Nutrition, TFA increase the risk of CVD. FAO/WHO point out not to intake much more TFA. 1994, USA CSIP required

39、 that FDA should take measure to TFA. 1999, FDA 64FR62746. 2004, FDA Issue.,Unnatural shape effects enzymes reduces eicosanoids Effects structure of cell membranes Increase LDLc Decrease HDLc Increase TG Increased CHD Impact Type II Diabetes Incorporate into brain cell and nerve cell membranes,Why a

40、re TFAs undesirable?,Source,Natural occurrence (biohydrogenation CLAs 3% of FAs) Milk products Tallow Hydrogenation of oils and fats (up to 35% of Fatty Acids) Margarines Frying fats Cooking/baking shortenings Salad oils Fillings frostings coatings Heating,Control,Hydrogenation Control Hydrogenation

41、 conditions New catalyzer SCF Reaction Interesterification Deodororising Soft Column Deodororising System The Dual Temperature Deodorizer Freeze-condensing vacuum systems for deodorization,Lower TFAs,Interesterification More stable vegetable oils Jelling or texture building agents Antioxidants to in

42、crease oil stability Blending of more stable vegetable oils with partially hydrogenated fats Reassessment of tropical oils and fats Combination of some or all of the above,Limits of TFA in Food,TFA5 in Lipid food, Holand and Sweden FDA Ruling Labels on all food and dietary supplements TFA 0.5 g/serv

43、ing can declare zero Currently no % Daily Value Low SFA food, TFA 0.5 g/serving Reduced SFA food, total of TFA and SFA below 25% Low Cholestero1 food， TFA and SFA below 2 g TFA and SFA above 4g, dont sign health claim,*intake of trans fat should be as low as possible,Revised Nutrition Facts PanelLis

44、ting Trans Fat,*,Foot note not mandated,高油脂食品体系的热加工过程具有复杂多样性 油脂会在热加工过程中发生反式异构化、热氧化、热裂解、环化、醚化、聚合等多种反应，形成各种有害产物。,高油脂食品加工过程产生的有害物,FOOD,Adsorption,Vaporization,Steam,Volatiles,Antioxidants,Steam,Solubilization,Colored compounds,Food lipids,Aeration,Oxidation,dienes,),Fission,Polymers, Alcohol,Changes oc

45、curring during deep fat frying,FOOD,Adsorption,Vaporization,Steam,Volatiles,Antioxidants,Steam,Hydrolysis,Free fatty acids,Mono,Diglyceride,Glycerin,Hydrolysis,Free fatty acids,Mono,Diacyglycerols,Solubilization,Colored compounds,Food lipids,Aeration,dienes,),Fission,Aeration,Hydroperoxides,(conjuga

46、ted,dienes,),Fission,Aldehydes,Hydrocarbons, Alcohol, Polymers,Heating(without oxygen ),Dimers, Cyclic compounds,TAG with MCFA,TAG with ketone and expoxide,Dimers,1025%,Volatile aldehydes 7%,Mechanism of carbonyl formation in frying oils by decomposition of hydroperoxide,RCHR (Glycerol),O O H,hydrop

47、eroxide,RCHO,Aliphatic aldehyde,CHO R(Glycerol),Glycerol type aldehyde,O,R-C-R (Glycerol),Glycerol type ketone,6883%,Cytotoxicity,R: methyl-terminal R: carbonyl-terminal,油脂聚合反应会生成二聚体、多聚体及环状化合物 油脂热加工过程中（120200）会产生高浓度的环氧乙烷，具有致癌性。 油脂的热分解反应生成各种挥发性物质，如醇、醛、酮及游离脂肪酸等极性化合物，损害人体的呼吸系统，典型刺激性气体是丙烯醛。 丙烯醛进一步氧化或脱水产

48、生丙烯酸，丙烯酸再与氨作用，最终会生成丙烯酰胺 油脂在受光、热、酸碱或催化剂及氧化剂的作用下，双键的位置和构型会发生变化，产生对人体健康具有严重影响的反式脂肪酸。,危害： 增加患心血管疾病的危险 导致患糖尿病的风险增加 导致必需脂肪酸缺乏 抑制婴幼儿生长发育 造成大脑功能衰退 来源： 油脂的氢化加工 油脂工艺脱臭 反刍动物肌肉脂肪及乳脂 食品的烹饪加工,反式脂肪酸,反式,顺式,气相色谱分离37种混合脂肪酸标准品,C18:1n9t（32.549min）,C18:2n6t (33.846min),调和油脂肪酸的主要成分,研究热点油脂加工工艺，减少反式脂肪酸 不同加热方式、不同食品体系中反式脂肪酸生

49、成规律,微波和传统加热处理过程中反式脂肪酸含量的变化,加热温度和时间对反式脂肪酸含量的影响,不论在微波加热还是传统加热过程中，反式脂肪酸都随着加热温度的增加而增加，在156之后更加剧烈。 微波加热条件下的变化比传统加热要更为剧烈。 微波加热提供的是一种微波能，使油脂产生更加剧烈的变化，降低顺反异构所需活化能，从而导致脂肪酸的顺反异构和裂解,反式脂肪酸,EATING HEALTH,提供能量 构成机体组织 提供必需脂肪酸 内分泌作用 帮助机体更有效地利用碳水化物和节约蛋白质作用 增加饱腹感、改善食物的感观性状、提供脂溶性维生素并促进维生素A、D、E、K的吸收,1.油脂是人体三大营养素之一,三大营养

50、素对人体的供能比,油脂营养与人体健康,2. 油脂营养价值的主要影响因素,脂肪酸组成 饱和脂肪酸、单不饱和脂肪酸、多不饱和脂肪酸（必需脂肪酸的含量） 天然微量营养成分及脂肪伴随物 脂溶性维生素、胆固醇、植物甾醇及甾醇酯、酚类等 没有或极少存在对人体健康有害的物质 农残、重金属残留、 反式脂肪酸、氧化副产物等 转基因油料油脂,脂溶性维生素：VA、VD、VE、VK，为机体必需有机化合物 甾 醇：植物甾醇预防心脑血管疾病 胆固醇是生物膜正常发挥作用的重要物质，过量摄入可导致心脑血管疾病 磷 脂：对生物膜的生理活性和机体的正常代谢有重要调节功能，如卵磷脂等 酚类物质：芝麻素具有降低血清胆固醇作用 花生中

51、白藜芦醇具有抗肿瘤，预防和治疗动脉粥样硬化和心脑血管疾病 色 素：叶绿素治疗慢性和急性胰腺炎；促进组织再生作用 类胡萝卜素中叶黄素、玉米黄素是眼睛视网膜的营养成分之一 其 他：米糠油中谷维素具有调节人体植物神经功能，促进生长发育等作用 二十八醇是全球公认的抗疲劳生理活性物质，改善心肌功能,（2）类脂物和脂质伴随物对人体健康的影响,（3）转基因食用油脂,转基因食品存在以下安全隐患 营养成分减少，英国伦理和毒性中心的试验报告表明转基因食品中对人体有益的成份减少了12%至14% 引起人体过敏反应 产生毒素或增加食品毒素含量，会导致某些遗传类疾病，奥地利政府于当地时间2008年11月11日发布最新科学

52、研究，首次证实转基因玉米会导致小白鼠繁殖能力下降 转基因油料作物：大豆、油菜和玉米等，目前在超市销售的大豆调和油90%以上的配料都采用的是转基因大豆色拉油,Vegetable oil - world supply - 68% Cocoa butter - solid fat Oil seeds - liquid oil Animal fat - 28% (from Hogs and Cattle) Marine oil - 4% Whale oil cod liver oil,DIETARY GUIDELINES 30% or less of all calories from fat 10%

53、 or less saturated 10% or less polyunsaturated At least 10% monosaturated Less than 300 mg of cholesterol daily,SFA:MUFA:PUFA 1：1：1 MUFA12 LA6 LNA1 EPA+DHA 0.5,-6/-3 WHO -6:-3 =510:1， Sweden -6:-3=5:1, Japan -6:-3=2-4:1， China -6:-3 =46:1 Dietary Food 1420 Canada -3 PUFA 1.2-1.6g/d America-3 PUFA1%，

54、0.5% from LNA， 0.5%from EPA+ DHA ；or LNA 2.2g/d， EPA+DHA0.65g/d，LA not above 6.7g/d NATO EPA +DHA 0.27%，or 0.8g/d,1.膳食推荐标准 FAO和WHO推荐人体能量摄入标准（2003）,膳食指南与食用油脂来源,膳食指南推荐标准（成年人，%能量）,多数国家油脂推荐摄入标准及限制成分的摄入量较为一致,中国膳食宝塔建议的食物量,2007年中国营养学会推荐的居民膳食指南： 油脂供能比为25%-30%，油脂总摄入量为30g-50g/天、食用油25g-30g/天,食物中脂肪的绝大部分来源于动物性食物、豆类、坚果和食用油,2.食用油来源与分布,畜肉中猪肉脂肪含量最高，分别达到30.8% 禽肉中鹅和鸭脂肪含量最高，分别为19.9%和19.7% 蛋类鸭蛋黄和鹅蛋黄油脂含量最高，分别为33.8%和26.4% 豆类制品豆腐干和腐竹油脂含量最高，分别为35.2%和27.2% 坚果与种子类山核桃和榛子仁油脂含量最高，分别为64.5%和52.9% 以畜肉中饱和脂肪酸含量较高，禽肉中单不饱和脂肪酸含量较高，鱼和坚果种子中多不饱和脂肪酸较高,按照食品中饱和脂肪酸的含量和中国膳食指南中推荐的膳食模式，因从食物中摄入的饱和脂肪酸占总能量的5%以上，根据饱和脂肪酸摄入量总能量10%的膳食标准，来源于