脂质的代谢生物化学英文版

1、22:14:142contentuNomenclature, structure and role of fatty acidsuFatty acid breakdownuFatty acid synthesisuTriacylglycerols.uCholesteroluPhospholipidsuLipoproteins .22:14:143guidancenkeystoneskeystones： 1. fat mobilization, -Oxidation of fatty acid. 2. Generation and utilization of ketone body, and

2、its physiological significance 3. Biotransformation of cholesterol 4. Classification, composition and functions of lipoproteins.ndifficultiesdifficulties： 1. process of fatty acid synthesis 2. metabolic pathways of lipoproteins. ndevelopment development ： abnormality of LDL metabolism and atheroscle

3、rosis (AS, 动脉粥样硬化。22:14:144K1 Structures and roles of fatty acids22:14:147pChain length: usually 14-24 carbon atoms, the most common FA: 16 or 18 C atoms.花生四烯酸花生四烯酸Fatty Acids Are Hydrocarbon Derivatives22:14:158 General formula of A saturated fatty acid : CH3(CH2)nCOOH, (n-an even number) bracket:

4、括号花生四烯酸花生四烯酸22:14:159 Mono-unsaturated fatty acids: one double bond in their structure, polyunsaturated fatty acids:two or more double bonds.The double bonds in polyunsaturated fatty acids are separated by at least one methylene group.methylene: 亚甲基(-CH2-)花生四烯酸花生四烯酸22:14:1510 The properties of fatty

5、 acids depend on their chain length and the number of double bonds.Shorter chain length fatty acids have lower melting temperatures than those with longer chains.Unsaturated fatty acids have lower melting temperatures than saturated fatty acids of the same chain length, whilst the corresponding poly

6、unsaturated fatty acids have even lower melting temperatures.octadecane: 十八烷十八烷酸: octadecanoate十八碳烯酸: octadecenoate十八碳二烯酸: octadecadienoate22:14:1512unsaturated fatty acids棕榈棕榈(软软)油酸油酸(palmitoleic acid)9-十六碳一烯酸十六碳一烯酸16:1-7CH3(CH2)5CHCH(CH2)7COOH油酸油酸(oleic acid)9-十八碳一烯酸十八碳一烯酸18:1 -9CH3(CH2)7CHCH(CH2)

7、7COOH亚油酸亚油酸(linoleic acid)9,12-十八碳二烯酸十八碳二烯酸18:2 -6CH3(CH2)4(CHCHCH2)2(CH2)6COOHa-亚麻酸亚麻酸(a-linolenic acid)9,12,15-十八碳三烯酸十八碳三烯酸18:3 -3CH3CH2(CHCHCH2)3(CH2)6COOH花生四烯酸花生四烯酸(arachidonic acid)5,8,11,14-二十碳四烯二十碳四烯酸酸20:4 -6CH3(CH2)4(CHCHCH2)4(CH2)2COOHCommon nameSystematic name碳原子数碳原子数和双键数和双键数簇簇formulasatur

8、ated fatty acids软脂酸软脂酸(palmitic acid)n-十六烷十六烷酸酸16:0CH3(CH2)14COOH硬脂酸硬脂酸(stearic acid)n-十八烷十八烷酸酸18:0CH3(CH2)16COOH22:14:1513 The systematic names for fatty acids are made by adding oic acid on to the name of the parent hydrocarbon. However, as fatty acids are ionized at physiological pH they are usua

9、lly written as RCOO, and have names ending in ate rather than oic acid. palmitate: 棕榈酸，软脂酸; palmitoleate: 软油酸; stearate: 硬脂酸; oleate: 油酸; linoleate: 亚油酸; linolenate: 亚麻酸; arachidonate: 花生四烯酸.22:14:1514 A C18 saturated fatty acid would be called octadecanoate, a C18 monounsaturated fatty acid octadec

10、enoate, and a C18 fatty acid with two double bonds octadecadienoate. However, many nonsystematic names are still in use (Table 1).octadecane: 十八烷; octadecanoate: 十八烷酸; octadecenoate: 十八碳烯酸; octadecadienoate: 十八碳二烯酸.22:14:1515Fatty Acids Are Hydrocarbon Derivativesa. Palmitate (C16, 软脂酸)b. Palmitolea

11、te (C16, 棕榈油酸)c. Stearate (C18, 硬脂酸)d. Oleate (C18, 油酸)e. Linoleate (C18, 亚油酸)f. Linolenate (C18, 亚麻酸)g. arachidonate: 花生四烯酸22:14:1516 There is also a shorthand notation to show the number of carbon atoms and the position of any double bonds in the structure.A fatty acid with 18 carbons and no doubl

12、e bonds is designated 18:0, while one with 18 carbons and two double bonds is 18:2.shorthand notation: 简化符号; The score was 9 to 6: 比分是九比六unsaturated fatty acids亚油酸亚油酸(linoleic acid)9,12-十八碳二烯酸十八碳二烯酸18:2 -6CH3(CH2)4(CHCHCH2)2(CH2)6COOHsaturated fatty acids硬脂酸硬脂酸(stearic acid)n-十八烷酸十八烷酸18:0CH3(CH2)16C

13、OOH22:14:1517 The carbon atoms in fatty acids are numbered from the carboxylic acid residue, and so the position of double bonds can be described using the number of the first carbon involved in the bond e.g. 9 shows a double bond between carbons 9 and 10 of the fatty acid chain.22:14:1518 The confi

14、guration of the double bonds in most unsaturated fatty acids is cis ; Thus, the full systematic name of linoleate is cis, cis-9, l2- octadecadienoate.22:14:1519pFatty acids have three major biological roles: They are used to make glycerophospholipids and sphingolipids that are essential components o

15、f biological membranes.3. Rolesglycerophospholipid: 甘油磷脂; sphingolipid: （神经）鞘脂类22:14:1620Structural Lipids in Membranes Triacylglycerols (三酰甘油) Phospholipids (磷脂) Glycolipids (糖脂) Archaebacterial ether lipids (古细菌醚脂)22:14:1621Fatty acids act as fuel molecules, u being stored as triacylglycerols, and

16、 u broken down to generate energy.TriacylglycerolTriacylglycerols Are Fatty Acid Esters of Glycerol豚鼠脂肪细胞拟南芥子叶细胞Triacylglycerols Provide Stored Energy and Insulation22:14:1622Many Foods Contain Triacylglycerols22:14:1623Derivatives of fatty acids serve as u hormones (such as the prostaglandins) and

17、u intracellular second messengers (such as DAG and IP3).花生四烯酸花生四烯酸前列腺素前列腺素E1白三烯白三烯A4血栓烷血栓烷Eicosanoids (类花生酸类花生酸) Carry Messages to Nearby Cells22:14:1624Lipids as Signals, Cofactors, and Pigments (色素色素)肌醇肌醇Phosphatidylinositol 4,5-bisphosphate磷脂酰肌醇磷脂酰肌醇 4,5-二磷酸二磷酸22:14:1626 They are derived from the

18、 common precursor arachidonate. This polyunsaturated fatty acid is a derivative of linoleate.花生四烯酸花生四烯酸前列腺素前列腺素E1白三烯白三烯A4血栓烷血栓烷Eicosanoids (类花生酸类花生酸) Carry Messages to Nearby Cells Prostaglandins: stimulate inflammation, modulate synaptic transmission between nerve cells, induce sleep. synapse: 突触;

19、synaptic transmission: 突触传递22:14:1627 Aspirin (acetylsalicylic acid) : to decrease inflammation, pain and fever, 1974, John Vane discovered how aspirin works. Aspirin inhibits the synthesis of prostaglandins by irreversibly inhibiting prostaglandin synthase. 22:14:1629ibuprofen: 布洛芬(抗炎、镇痛药); fenbid:

20、 芬必得(布洛芬缓释胶囊); cyclooxygenase: 加环氧酶22:14:1630Problems1. Major biological roles of fatty acids.2. Essential fatty acid.3. Common precursor of PG, TXA2 and LTs.4. Derivative of linoleate.22:14:1731Continued Lipid Metabolism22:14:173222:14:1733Processing of dietary lipids in vertebrates.Digestion, Mobi

21、lization (动员动员), and Transport of Fats脂肪动员Mobilization of triacylglycerols stored in adipose tissue.Digestion, Mobilization (动员动员), and Transport of FatsK2 fatty acid breakdown22:14:1737Three stages of fatty acid oxidation. the oxidation of long-chain fatty acids to acetyl-CoA (-oxidation); the oxid

22、ation of acetyl-CoA to CO2 in the citric acid cycle; the transfer of electrons from reduced electron carriers to the mitochondrial respiratory chain.脂酰脂酰CoA合成酶合成酶ATP AMP PPi 脂脂 肪肪 酸酸RCHRCH2 2CHCH2 2C C- -OH OH OO=OO=脂脂 酰酰SCoARCHRCH2 2CHCH2 2C CSCoA SCoA OO=OO=Acyl-CoA synthetase exists in the outer

23、membrane of ER and mitochondria.脂酰脂酰CoA合成酶合成酶ATP AMP PPi 脂脂 肪肪 酸酸RCHRCH2 2CHCH2 2C C- -OH OH OO=OO=脂脂 酰酰SCoARCHRCH2 2CHCH2 2C CSCoA SCoA OO=OO=Acyl-CoA synthetase exists in the outer membrane of ER and mitochondria.Fatty Acids Are Activated and Transported into Mitochondria22:14:1844 The acylcarniti

24、ne is then transported across the inner mitochondrial membrane by a carnitine/acylcarnitine translocase.This integral membrane transport protein transports acylcarnitine molecules into the mitochondrial matrix and free carnitine molecules out.translocase: 转位酶Fatty acid entry into mitochondria via th

25、e acyl-carnitine/carnitine (肉碱肉碱) transporter肉碱脂酰转移酶肉碱脂酰转移酶 I : rate-limiting enzyme Acyl CoA dehydrogenase (脂酰辅酶脂酰辅酶A脱氢酶脱氢酶) Enoyl CoA hydratase (烯脂酰辅酶烯脂酰辅酶A水化酶水化酶) Hydroxyacyl CoA dehydrogenase (羟脂酰辅酶羟脂酰辅酶A脱氢酶脱氢酶) Beta-ketothiolase (硫解酶硫解酶)(1) The Oxidation of Saturated Fatty Acids Has Four Basic

26、Steps脂酰辅酶脂酰辅酶A A脱氢酶脱氢酶反式烯脂酰辅酶反式烯脂酰辅酶A A(C16)棕榈酰辅酶棕榈酰辅酶A AOxidation烯脂酰辅酶烯脂酰辅酶A A水化酶水化酶羟脂酰辅酶羟脂酰辅酶A AHydration羟脂酰辅酶羟脂酰辅酶A A脱氢酶脱氢酶酮脂酰辅酶酮脂酰辅酶A AOxidation硫解酶硫解酶脂酰辅酶脂酰辅酶A A乙酰转移酶乙酰转移酶豆蔻酰辅酶豆蔻酰辅酶A A(C14)乙酰辅酶乙酰辅酶A AThiolysis MultistepC16 ( Palmitoyl-CoA )C16 ( Palmitoyl-CoA )Oxidation of Fatty Acids棕榈酰辅酶棕榈酰辅酶A

27、豆蔻酰辅酶豆蔻酰辅酶A烯脂酰辅酶烯脂酰辅酶A A异构酶异构酶单不饱和脂肪酸单不饱和脂肪酸Oxidation of Unsaturated Fatty Acids Requires Two Additional Reactions烯脂酰辅酶烯脂酰辅酶A A异构酶异构酶单不饱和脂肪酸单不饱和脂肪酸Oxidation of Unsaturated Fatty Acids Requires Two Additional Reactionsoleate: 油酸; oleoyl: 油酰; dodecenoyl: 十二烯酰烯脂酰辅酶烯脂酰辅酶A A异构酶异构酶多不饱和脂肪酸多不饱和脂肪酸linoleate:

28、 亚油酸; linoleoyl: 亚油酰2,4-2,4-二烯脂酰辅酶二烯脂酰辅酶A A还原酶还原酶烯脂酰辅酶烯脂酰辅酶A A异构酶异构酶烯脂酰辅酶烯脂酰辅酶A A异构酶异构酶多不饱和脂肪酸多不饱和脂肪酸Complete Oxidation of Odd-Number (奇数奇数) Fatty Acids Requires Three Extra Reactionspropionyl: 丙酰; 丙酰辅酶丙酰辅酶A A羧化酶羧化酶甲基丙二酸单酰辅酶甲基丙二酸单酰辅酶A A差向异构酶差向异构酶D-D-甲基丙二酸单酰辅酶甲基丙二酸单酰辅酶A A 108- 2 (PPi) = 106Energy yie

29、ld:肉碱脂酰转移酶肉碱脂酰转移酶 I肉碱脂酰转移酶肉碱脂酰转移酶 I丙二酸单酰辅酶丙二酸单酰辅酶A丙二酸单酰辅酶丙二酸单酰辅酶AFatty Acid Oxidation Is Tightly Regulated硫解酶硫解酶脂酰辅酶脂酰辅酶A乙酰转移酶乙酰转移酶豆蔻酰辅酶豆蔻酰辅酶A乙酰辅酶乙酰辅酶A羟脂酰辅酶羟脂酰辅酶A脱氢酶脱氢酶酮脂酰辅酶酮脂酰辅酶AFeedback regulation of products(酮体酮体)丙酮丙酮乙酰乙酸乙酰乙酸羟基丁酸羟基丁酸硫解酶CO2 CoASH CoASH NAD+ NADH+H+ -羟丁酸羟丁酸脱氢酶脱氢酶HMGCoA 合酶合酶乙酰乙酰乙酰乙酰

30、CoA硫解酶硫解酶HMGCoA 裂解酶裂解酶CHCH3 3CSCoA CSCoA = =OOCHCH3 3CSCoA CSCoA = =OO= =OOCHCH3 3CSCoA CSCoA = =OOCHCH3 3CSCoA CSCoA = =OO= =OOCHCH3 3CCHCCH2 2CSCoA CSCoA ( (乙乙酰酰乙乙酰酰乙乙酰酰乙乙酰酰CoACoA) )= =OO= =OOCHCH3 3CCHCCH2 2CSCoA CSCoA ( (乙乙酰酰乙乙酰酰乙乙酰酰乙乙酰酰CoACoA) )= =OO= =OO= =OO= =OOHOCCHHOCCH2 2CCHCCH2 2CSCoACSC

31、oA( (HMGCoAHMGCoA) ) CHCH3 3OHOH羟羟甲甲基基戊戊二二酸酸单单酰酰羟羟甲甲基基戊戊二二酸酸单单酰酰CoACoA= =OO= =OOHOCCHHOCCH2 2CCHCCH2 2CSCoACSCoA( (HMGCoAHMGCoA) ) CHCH3 3OHOH羟羟甲甲基基戊戊二二酸酸单单酰酰羟羟甲甲基基戊戊二二酸酸单单酰酰CoACoA= =OO= =OO= =OO= =OOCHCH3 3CHCHCHCH2 2COOH COOH D(D(- -) )- - - -羟羟丁丁酸酸羟羟丁丁酸酸OHOHCHCH3 3CHCHCHCH2 2COOH COOH D(D(- -) )-

32、 - - -羟羟丁丁酸酸羟羟丁丁酸酸CHCH3 3CHCHCHCH2 2COOH COOH D(D(- -) )- - - -羟羟丁丁酸酸羟羟丁丁酸酸OHOHCHCH3 3CCHCCH3 3 丙丙酮酮丙丙酮酮= =OOCHCH3 3CCHCCH3 3 丙丙酮酮丙丙酮酮CHCH3 3CCHCCH3 3 丙丙酮酮丙丙酮酮= =OO= =OOCHCH3 3CCHCCH2 2COH COH 乙乙酰酰乙乙酸酸乙乙酰酰乙乙酸酸= =OO= =OOCHCH3 3CCHCCH2 2COH COH 乙乙酰酰乙乙酸酸乙乙酰酰乙乙酸酸= =OOCHCH3 3CCHCCH2 2COH COH 乙乙酰酰乙乙酸酸乙乙酰酰

33、乙乙酸酸CHCH3 3CCHCCH2 2COH COH 乙乙酰酰乙乙酸酸乙乙酰酰乙乙酸酸= =OO= =OO= =OO= =OO-Hydroxybutyrate as a fuel. Ketone body formation and export from the liver.22:14:2586Continued Lipid Metabolism22:14:2588K3 Fatty acid synthesisn Fatty acid biosynthesis and breakdown uoccur by different pathwaysucatalyzed by different

34、 sets of enzymesutake place in different parts of the celln Biosynthesis requires the participation of a three-carbon intermediate, malonyl-CoA, unot involved in fatty acid breakdown.丙二酸单酰辅酶丙二酸单酰辅酶A 22:14:2696基质基质细胞质细胞质柠檬酸柠檬酸柠檬酸合酶柠檬酸合酶草酰乙酸草酰乙酸苹果酸苹果酸丙酮酸丙酮酸Shuttle for transfer of acetyl groups from mi

35、tochondria to the cytosoll（1） snythesis of malonyl CoAThe acetyl-CoA carboxylase reactionbiotin carrier protein lAcetyl-CoA carboxylase has three functional regions: biotin carboxylasetranscarboxylase生物素羧化酶生物素羧化酶转羧酶转羧酶转羧酶转羧酶生物素羧化酶生物素羧化酶丙二酸单酰丙二酸单酰CoAThe acetyl-CoA carboxylase reactionlThree functiona

36、l regions : biotin carrier proteinbiotin carboxylasetranscarboxylase.22:14:28104（2） fatty acid synthesis22:14:2810622:14:28108泛酸泛酸4-磷酸磷酸泛酰泛酰巯基巯基乙胺乙胺Acyl carrier protein (ACP, 酰基载体蛋白酰基载体蛋白)AT: Acetyl-CoA-ACP transacetylase22:14:30116Beginning of the second round of the fatty acid synthesis cycle.22:1

37、4:30118 This molecule is not accepted by the acyl-malonyl-ACP condensing enzyme, and so cannot be elongated further by this process. Instead it is hydrolyzed by a thioesterase to give palmitate and ACP.thioesterase: 硫酯酶22:14:30119 The overall stoichiometry for the synthesis of palmitate is:8acetyl C

38、oA + 7ATP + 14NADPH + 14H+palmitate + 14NADP+ + 8CoA + 6H2O +7ADP +7Pistoichiometry: 化学计算（法）(palmitate: 16C saturated fatty acid) Each of the seven rounds: one ATP (used in the synthesis of malonyl-ACP) two NADPH (used in the reduction reactions)Biosynthesis of Fatty AcidsThen seven cycles of conden

39、sation and reduction:The overall process is:The formation of seven malonyl-CoA molecules:（3） elongation of fatty acids beyond C16 palmitateH+NADH NAD+ E-FAD E-FADH2 Fe2+ Fe3+ Fe2+ Fe3+ 油酰油酰CoA+2H2O 硬脂酰硬脂酰CoA+O2 NADH-cytb5 reductase (还原酶还原酶)Desaturase(去饱和酶去饱和酶) Cytb5 Saturatedfatty acylCoAMonounsatur

40、atedfatty acylCoAstearyl: 硬脂酰硬脂酰; oleoyl: 油油酰 花生四烯酸花生四烯酸前列腺素前列腺素E1白三烯白三烯A4血栓烷血栓烷snythesis of malonyl CoA:(1) Regulation by metabolites(2) Regulation by hormonesglucagonepinephrineinsulin乙酰辅酶乙酰辅酶A丙二酸单酰辅酶丙二酸单酰辅酶ARegulation of fatty acid synthesis丙二酸单酰辅酶丙二酸单酰辅酶A22:14:32133Continued Lipid Metabolism22:1

41、4:32134K4 TriacylglycerolsMany Foods Contain Triacylglycerols豚鼠脂肪细胞22:14:33140 Lipoproteins: Triacylglycerols are transported round the body in large lipid-protein particles lipoproteins. 豚鼠脂肪细胞Triacylglycerols Provide Stored Energy and Insulationglycerol 3-phosphate(Rate-limiting enzyme)22:14:33143

42、ATP is not involved in the biosynthesis of TG. Instead the reactions are driven by the cleavage of the high-energy thioester bond between the acyl moiety and CoA.Both phosphatidic acid (phosphatidate) and DAG are also used in the synthesis of membrane phospholipids.moiety: （两部分组成的事物的）一部分22:14:33145l

43、ipin (lipid): 脂质，脂类; perilipin: 外周脂质脂肪动员(是指储存在脂肪细胞中的脂是指储存在脂肪细胞中的脂肪，被肪脂酶逐步水解为肪，被肪脂酶逐步水解为FFA及及甘油甘油并释放入血以供其他并释放入血以供其他组织氧化利用的过程。组织氧化利用的过程。)Mobilization of triacylglycerols stored in adipose tissue.Lipids stored in adipose tissue were gradually hydrolyzed into FFA and glycerol by lipases，then released in

44、to blood and transported to other tissue cells for producing energy via oxidation.Refers to the process that:22:14:33146 The glycerol backbone is also utilized, being transformed into dihydroxyacetone phosphate, an intermediate in glycolysis. This requires two enzymes, glycerol kinase, which uses AT

45、P to phosphorylate glycerol, producing glycerol 3-phosphate, and glycerol 3-phosphate dehydrogenase which produces dihydroxyacetone phosphate.(DHAP)22:14:33147 In the intestine, dietary fats are hydrolyzed by pancreatic lipase and the released fatty acids taken up into the intestinal cells. Both the

46、 digestion and uptake processes are aided by the detergent-like properties of the bile salts.22:14:34148Processing of dietary lipids in vertebrates.22:14:34150Mobilization of triacylglycerols stored in adipose tissue. The catabolic (lipolytic) hormones: glucagon, epinephrine and norepinephrine bind

47、to receptor proteins on the cell surface and increase the levels of cAMP in adipose cells through activation of adenylate cyclase. 22:14:34151 The cAMP allosterically activates cAMP-dependent protein kinase (protein kinase A) which phosphorylates various intracellular enzymes including hormone-sensi

48、tive lipase.Mobilization of triacylglycerols stored in adipose tissue.22:14:34152 Phosphorylation of hormone-sensitive lipase activates it, thereby stimulating the hydrolysis of triacylglycerols, raising the levels of free fatty acids (FFA) in the blood.Mobilization of triacylglycerols stored in adi

49、pose tissue.22:14:34153 22:14:34154 In mammals, triacylglycerol molecules are broken down and resynthesized in a triacylglycerol cycle during starvation. Approximately 75% of all fatty acids released by lipolysis are reesterified to form triacylglycerols rather than used for fuel.22:14:34155 The app

50、arently futile triacylglycerol cycle is sustained via metabolism in two separate organs (adipose tissue and liver) and is coordinately regulated.Futile CycleThe triacylglycerol cycle. function: represent an energy reserve in the bloodstream during starvation, more rapidly mobilized in a “fight or fl

51、ight” emergency than would stored triacylglycerol in adipose tissue.22:14:34156 What is the source of the glycerol 3-phosphate required for this process during starvation? As noted above, glycolysis is suppressed in these conditions by the action of glucagon and epinephrine, so little DHAP is available.dihydroxyacetone phosphate: 磷酸二羟丙酮 (DHAP)Glyceroneogenesis22:14:35158Regulation of glyceroneogenesisFutile CycleHSLGlyceroneogenesis is regulated reciprocally in the liver and adipose tissue, affecting lipid m