生物活性脂质

1、 Definition and Classification Fatty Acids Glycerolipids Glycerophospholipids Sphingolipids Case Studies Stored Energy Structural Lipids in Membranes as Signals, Cofactors, and Pigments Fatty acids: saturated, unsaturated (C4 to C36). Glycerolipids: mono-, di-, and tri-substituted glycerols Glycerop

2、hospholipids: phospholipids Sphingolipids: common structural feature, a sphingoid base backbone Most naturally occurring fatty acids have a chain of an even number of carbon atoms, from 4 to 28. Length of free fatty acid chains: Short-chain fatty acids (SCFA) , 22 carbons. Specify the chain length a

3、nd number of double bonds, separated by a colon. The 16-carbon saturated palmitic acid is abbreviated 16:0. The positions of any double bonds are specified by superscript numbers following (delta); a 18-carbon fatty acid with one double bond between C-9 and C-10 (C-1 being the carboxyl carbon) and a

4、nother between C-12 and C-13 is designated 18:2( 9,12). The xth is assigned to the number of the first double bond located on carboncarbon bond, counting from the terminal methyl carbon (designated as n or ) toward the carbonyl carbon. The physiological properties of unsaturated fatty acids largely

5、depend on the position of the first unsaturation relative to the end position and not the carboxylate. -Linolenic acid is classified as a n3 or omega-3 fatty acid. The most commonly researched fatty acid biosynthetic pathways are n3 and n6. Humans must ingest because the body requires them for good

6、health but cannot synthesize them. Only two EFAs are known for humans: alpha-linolenic acid (an omega-3 fatty acid) and linoleic acid (an omega-6 fatty acid). Other fatty acids are only conditionally essential including gamma-linolenic acid (an omega-6 fatty acid), lauric acid (a saturated fatty aci

7、d), and palmitoleic acid (a monounsaturated fatty acid).linoleic acidgamma-linolenic acid Polyunsaturated fatty acids (PUFAs), fatty acids that contain more than one double bond. eicosapentaenoic acid or EPA (20:5, n-3) docosahexaenoic acid or DHA (22:6, n-3)EPADHA Since the 1930s, omega-3 fatty aci

8、ds have been known as essential to normal growth and health. Awareness of their health benefits has dramatically increased since the 1990s. DHA and EPA were discovered in the 1970s by researchers studying the Greenland Inuit Tribe. The Greenland Inuit people consumed large amounts of fat from meat,

9、but displayed virtually no cardiovascular disease. A small amount of n3 in the diet (1% of total calories) enabled normal growth, and increasing the amount had little to no additional effect on growth. n6 was better at supporting dermal integrity, renal function, and parturition. The ingested ratio

10、of n6 to n3 (especially linoleic vs alpha-linolenic) fatty acids is important to maintaining cardiovascular health. Optimal ratio of n6:n3 is 4:1 or lower. The ratios of n6 to n3 fatty acids in some common vegetable oils are: canola 2:1, soybean 7:1, olive 313:1, sunflower (no n3), flax 1:3, cottons

11、eed (almost no n3), peanut (no n3), grapeseed oil (almost no n3) and corn oil 46:1 ratio of n6 to n3. On September 8, 2004, the U.S. FDA gave qualified health claim status to EPA and DHA n3 fatty acids, stating that supportive but not conclusive research shows that consumption of EPA and DHA n3 fatt

12、y acids may reduce the risk of coronary heart disease.“ The Canadian Government permits the following biological role claim for DHA: DHA, an omega-3 fatty acid, supports the normal development of the brain, eyes and nerves. Nutritionally important n3 fatty acids include -linolenic acid (ALA), eicosa

13、pentaenoic acid (EPA), and docosahexaenoic acid (DHA). Mammalian brains are also an extremely rich source of not only n-3 fatty acids in general, but DHA in particular. Mammals cannot synthesize n3 fatty acids, but have a limited ability to form the long-chain n3 fatty acids EPA (20-carbon atoms) an

14、d DHA (22-carbon atoms) from the short-chain eighteen-carbon n3 fatty acid ALA. The short-chain n3 fatty acids are converted to long-chain forms (EPA, DHA) with an efficiency below 5% in men, and at a greater percentage in women which may be due to the importance for meeting the demands of the fetus

15、 and neonate for DHA. Fish oil: Heavy metal poisoning by the bodys accumulation of traces of heavy metals, in particular mercury, lead, nickel, arsenic, and cadmium, is a possible risk. Other contaminants (PCBs, furans, dioxins, and PBDEs) might be found, especially in less-refined fish oil suppleme

16、nts. The FDA recommends that the total dietary intake of n3 fatty acids from fish not exceed 3 grams per day, with no more than 2 grams per day from nutritional supplements. Flaxseed and its oil are perhaps the most widely available botanical source of the n3 fatty acid ALA. Flaxseed oil consists of

17、 approximately 55% ALA, which makes it six times richer than most fish oils in n3 fatty acids, although it contains negligible amounts of EPA and DHA, the n-3 fatty acids that FDA considers healthful. On october 31, 2000, the United States FDA noted that known or suspected risks of EPA and DHA consu

18、med in excess of 3 grams per day may include the possibility of: Increased incidence of bleeding Hemorrhagic stroke Oxidation of omega-3 fatty acids Increased levels of low-density lipoproteins (LDL) cholesterol or apoproteins associated with LDL cholesterol among diabetics and hyperlipidemics Reduc

19、ed glycemic control among diabetics In the early 20th century, soybeans began to be imported into the U.S. as a source of protein. Soybean oil was turned into a solid one by hydrogenation to resolve shortage of butter. Trans fat is mainly produced during hydrogenation. As early as 1956 there were su

20、ggestions in the scientific literature that trans fats could be a cause of the large increase in coronary artery disease. Studies in the early 1990s, however, brought renewed scrutiny and confirmation of the negative health impact of trans fats. The National Academy of Sciences recommended that tran

21、s fatty acid consumption be as low as possible while consuming a nutritionally adequate diet. The elimination of trans fat from the diet is not recommended because trans fat is naturally present in many animal foods in trace quantities, and therefore its removal from ordinary diets might introduce u

22、ndesirable side effects and nutritional imbalances if proper nutritional planning is not undertaken. On July 11, 2003, FDA issued a regulation requiring manufacturers to list trans fat on the Nutrition Facts panel of foods and some dietary supplements. Trans fat levels of less than 0.5 grams per ser

23、ving can be listed as 0 grams trans fat on the food label. In most eukaryotic cells, triacylglycerols form a separate phase of microscopic, oily droplets in the aqueous cytosol, serving as depots of metabolic fuel. Adipocytes and germinating seeds contain lipases, enzymes that catalyze the hydrolysi

24、s of stored triacylglycerols, releasing fatty acids for export to sites where they are required as fuel. Humans have fat tissue (composed primarily of adipocytes) under the skin, in the abdominal cavity, and in the mammary glands. The human body can store less than a days energy supply in the form o

25、f glycogen. Glycerol monolaurate (GML) occurring naturally in breast milk is a surfactant that has potential use as an additive to tampons and wound dressings to reduce the incidence of certain bacterial toxin-mediated illnesses. The central architectural feature of biological membranes is a double

26、layer of lipids, which acts as a barrier to the passage of polar molecules and ions. Membrane lipids are amphipathic. Common types of membrane lipids: glycerophospholipids, galactolipids and sulfolipids, archaebacterial tetraether lipids, sphingolipids The fatty acids in glycerophospholipids can be

27、any of a wide variety. The distribution of molecular species is specific for different organisms, different tissues of the same organism, and different glycerophospholipids in the same cell or tissue. The biological significance of the variation in fatty acids and head groups is seldom understood. T

28、he polar alcohol in the head group may be negatively charged, neutral, or positively charged. These charges contribute greatly to the surface properties of membranes. It stimulates platelet aggregation and the release of serotonin (a vasoconstrictor) from platelets. It also exerts a variety of effec

29、ts on liver, smooth muscle, heart, uterine, and lung tissues and plays an important role in inflammation and the allergic response. They are probably the most abundant membrane lipids in the biosphere. The evolutionary pressure to conserve phosphate for more critical roles favored plants made phosph

30、ate free lipids. In humans, at least 60 different sphingolipids have been identified in cellular membranes. The carbohydrate moieties of certain sphingolipids define the human blood groups and therefore determine the type of blood that individuals can safely receive in blood transfusions. Sphingomye

31、lins are present in the plasma membranes of animal cells and are especially prominent in myelin, a membranous sheath that surrounds and insulates the axons of some neurons. Glycosphingolipids, which occur largely in the outer face of plasma membranes Gangliosides, the most complex sphingolipids, are

32、 concentrated in the outer surface of cells, where they present points of recognition for extracellular molecules or surfaces of neighboring cells. Glycosphingolipids as determinants of blood groups. It has been well established that increased serum/plasma cholesterol levels was positively correlate

33、d with coronary heart disease. The relationship between dietary fats and serum cholesterol has been studied extensively for more than three decades. TC = 2.7S 1.35P + 1.5C1/2 (Key et al 1965) TC denotes the change in serum total cholesterol in mg/100mL serum. S and P denote the change in % energy in

34、 intake of SFA and PUFA, respectively. C is the change in dietary cholesterol in mg/1000 kcal per day. It has been established that the SFAs lauric (12:0), myristic (14:0) and palmitic acid (16:0) are equally cholesterolemic, fatty acids with carbon chain lengths of less than 12 have little effect o

35、n blood cholesterol. While the SFA stearic acid (18:0) and monounsaturated oleic acid (18:1) are neutral. The polyunsaturated fatty acids, principally linoleic acid (18:2n-6) are regarded as cholesterol lowering. Recent animal studies on blood lipids and lipoproteins showed C12-C16 saturates were no

36、t equally cholesterolemic. Pronczuk et al. (1991) reported that coconut oil was hypercholesterlemic when compared with tallow, lard and butter, the latter three “saturated fats” were not significantly more cholesterolemic than “polyunsaturated” corn oil. The fatty acid composition of these fats reve

37、aled that coconut oil is rich in the 12:0+14:0, whereas lard and tallow were rich in the 16:0. Dietary intervention studies have found that increase in blood cholesterol levels was highest with 12:0+14:0, moderate with 16:0, and lowest with 18:0 (Tholstrup et al. 1994, Sundram et al. 1994). The 12:0

38、 and 16:0 may be equal (Denke & Grundy 1992, Dougherty & Icano 1992, Temme et al. 1996). The 14:0 was more hypercholesterolemic than 16:0 (Zock et al. 1994). The 16:0 and 18:1 have an equal effect on normocholesterolemic subjects (Becker et al. 1983, Ng et al. 1992, Ghafoorunissa et al. 1995

39、). The 14:0 is the only saturates which raises plasma cholesterol when lipoprotein metaboolism and LDL receptor activity is normal. The aim of this study was to investigate the serum Lp(a) levels, PUFA status and correlates of serum Lp(a) in healthy female vegetarians and omnivores. An cross-section

40、al study in free-living healthy female subjects have been conducted. Cross-sectional comparison Free living subjects: 74 females, aged 20-55 years,50 vegetarians 24 omnivores Each volunteer completed a 12-day food record and a questionnaire,gave a blood sampleFatty acidVegetarianOmnivoresp-value18:2

41、n-620:3n-620:4n-622:4n-622:5n-6Total n-618:3n-320:5n-322:5n-322:6n-3Total n-3n-3/n-629.0 7.0 3.3 1.110.4 3.0 0.5 0.1 0.3 0.143.5 8.7 0.3 0.1 0.7 0.4 1.0 0.3 3.2 1.2 5.2 1.70.12 0.0432.5 8.1 4.5 1.113.7 3.9 0.5 0.1 0.3 0.151.5 12.0 0.3 0.2 1.3 0.8 1.2 0.3 4.8 1.2 7.6 2.20.15 0.030.120.00060.0030.730.

42、010.020.340.0050.150.000040.00030.01Serum phospholipid fatty acid (mg/100g)(Clin Sci, 97, 175-181, 1999)Serum Lp(a)(mg/L)VegetariansOmnivores01002003003000102030405060Lp(a) mg/LPercentage of subjectsOmnivoresVegetarian(Clin Sci, 97, 175-181, 1999)Plasma total cholesterol (mmol/L) VegetariansOmnivore

43、s 012345p0.05-2000200400600800100012002.533.544.555.566.57Plasma total cholesterol (mmol/L)Y = -86.151 + 70.073 * Xr = 0.25p = 0.048 Lp(a)(mg/L)(Clin Sci, 97, 175-181, 1999) The aim of this study was to investigate the vegetarians who consume an increased dietary ALA exhibit a raised tissue n-3 PUFA

44、 and decreased AA/EPA ratio, decreased plasma 11-dehydro TXB2 concentration and reduced in vitro platelet aggregation. Twenty two free -living aged 20-50 (36 7) , non-cigarette smoking healthy male vegetarian recruited from Melbourne metropolitan area.Low ALAMedium ALAHigh ALADay 0Day 14Day 42food r

45、ecord for 8 dfood record for 7 dfood record for 7 dpre-experimental(Am J Clin Nutr, 69, 872-882, 1999)Dietary fat intake (g/d)(Am J Clin Nutr, 69, 872-882, 1999)Mode. ALA group High ALA groupParameterDay 14Day 42Day 14 Day 42TAG (mmol/L)1.26 0.481.38 0.530.77 0.210.80 0.39TC (mmol/L)4.54 1.124.63 1.

46、254.36 0.684.26 0.55LDL-C (mmol/L)2.94 0.912.96 1.122.74 0.522.74 0.33HDL-C (mmol/L)1.12 0.241.14 0.231.33 0.331.22 0.2611-deH TXB2 (ng/L) 37.4 6.536.0 7.936.2 6.544.9 15.5Biochemical parameters(Am J Clin Nutr, 69, 872-882, 1999)Mode. ALA group High. ALA groupParameterDay 14Day 42Day 14Day 42Fib (g/

47、L) 2.4 0.5 2.3 0.5 2.3 0.6 2.4 0.5Factor VII (%) 99 25 99 28 96 12 99 14PLT (x109/L)208 37196 50233 75223 58MPV (fL) 8.7 1.0 9.2 1.3 8.7 1.2 8.7 0.8Haematological parameters(Am J Clin Nutr, 69, 872-882, 1999)Mode. ALA group High ALA groupAgonistsDay 14Day 42Day 14Day 42Collagen (2 mg/L) 12.2 3.213.4

48、 4.816.5 3.115.7 3.9AA (1.0 mmol/L) 9.6 4.511.6 5.413.9 4.714.9 3.6ADP (8 mol/L) 7.2 3.2 8.3 3.311.2 4.510.8 3.4ADP (17 mol/L)10.3 2.810.3 3.312.9 4.612.6 3.3Agonists induced platelet aggregation(Am J Clin Nutr, 69, 872-882, 1999)Platelet PL n-3 PUFA (% of total FA)(Am J Clin Nutr, 69, 872-882, 1999

49、)Platelet PL n-6 PUFA (% of total FA)(Am J Clin Nutr, 69, 872-882, 1999)Plasma PL n-3 PUFA (% of total FA)(Am J Clin Nutr, 69, 872-882, 1999)Plasma TAG n-3 PUFA (% of total fatty acid)(Am J Clin Nutr, 69, 872-882, 1999)CanolaLinseedRed meatFish012BaselineEndpoint*p0.05,*p0.001*Effect of different di

50、et on platelet PL EPA levels(Am J Clin Nutr, 69, 872-882, 1999)Effect of different diet on platelet PL DPA levelsCanolaLinseedRed meatFish0123BaselineEndpoint*p0.001*(Am J Clin Nutr, 69, 872-882, 1999)Relationship between platelet PL PUFA and intake of fish, meat and PUFA The aims of this study were

51、 to investigate: (1) platelet phospholipid (PL) polyunsaturated fatty acid (PUFA) composition in subjects who were the Melbourne Chinese migrants compared with those who were the Melbourne Caucasians, (2) the relationship between platelet PL PUFA and intake of fish, meat and PUFA. The 97 Melbourne C

52、hinese males aged 25 to 55y and 78 age and sex matched Caucasians. Each volunteer completed a semi quantitative FFQ and gave a blood sample. Chinese Caucasians p-valueEnergy (MJ)7.95 2.0312.49 3.430.0001Fat (% of E)25.2 5.4 33.9 6.00.0001Fat (g/d) 54 18 114 420.0001SFA (% of Fat)41.7 4.6 44.1 5.0 0.0004MUFA (% of Fat)43.1 3.1 40.0 3.40.0001PUFA (% of Fat)15.1 4.4 16.0 4.1 0.078Daily dietary intakes (Eur J Clin Nutr, 55, 1036-1042, 2001) ChineseCaucasiansp-valueRed meat (g/d) 37 28146 950.0001White meat (g/d) 87 54 67 410.004