脂質(zhì)的代謝生物化學(xué)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, 動脈粥樣硬化。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、括號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: 亞甲基(-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棕櫚棕櫚(軟軟)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亞油酸亞油酸(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-亞麻酸亞麻酸(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碳原子數(shù)碳原子數(shù)和雙鍵數(shù)和雙鍵數(shù)簇簇formulasatur

8、ated fatty acids軟脂酸軟脂酸(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: 棕櫚酸，軟脂酸; palmitoleate: 軟油酸; stearate: 硬脂酸; oleate: 油酸; linoleate: 亞油酸; linolenate: 亞麻酸; 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, 軟脂酸)b. Palmitolea

11、te (C16, 棕櫚油酸)c. Stearate (C18, 硬脂酸)d. Oleate (C18, 油酸)e. Linoleate (C18, 亞油酸)f. Linolenate (C18, 亞麻酸)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: 簡化符號; The score was 9 to 6: 比分是九比六unsaturated fatty acids亞油酸亞油酸(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: （神經(jīng)）鞘脂類22:14:1620Structural Lipids in Membranes Triacylglycerols (三酰甘油) Phospholipids (磷脂) Glycolipids (糖脂) Archaebacterial ether lipids (古細菌醚脂)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豚鼠脂肪細胞擬南芥子葉細胞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 (類花生酸類花生酸) 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 (類花生酸類花生酸) Carry Messages to Nearby Cells Prostaglandins: stimulate inflammation, modulate synaptic transmission between nerve cells, induce sleep. synapse: 突觸;

19、synaptic transmission: 突觸傳遞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、鎮(zhèn)痛藥); fenbid:

20、 芬必得(布洛芬緩釋膠囊); cyclooxygenase: 加環(huán)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 (動員動員), and Transport of Fats脂肪動員Mobilization of triacylglycerols stored in adipose tissue.Digestion, Mobilization (動員動員), 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: 轉(zhuǎn)位酶Fatty acid entry into mitochondria via th

25、e acyl-carnitine/carnitine (肉堿肉堿) transporter肉堿脂酰轉(zhuǎn)移酶肉堿脂酰轉(zhuǎn)移酶 I : rate-limiting enzyme Acyl CoA dehydrogenase (脂酰輔酶脂酰輔酶A脫氫酶脫氫酶) Enoyl CoA hydratase (烯脂酰輔酶烯脂酰輔酶A水化酶水化酶) Hydroxyacyl CoA dehydrogenase (羥脂酰輔酶羥脂酰輔酶A脫氫酶脫氫酶) Beta-ketothiolase (硫解酶硫解酶)(1) The Oxidation of Saturated Fatty Acids Has Four Basic

26、Steps脂酰輔酶脂酰輔酶A A脫氫酶脫氫酶反式烯脂酰輔酶反式烯脂酰輔酶A A(C16)棕櫚酰輔酶棕櫚酰輔酶A AOxidation烯脂酰輔酶烯脂酰輔酶A A水化酶水化酶羥脂酰輔酶羥脂酰輔酶A AHydration羥脂酰輔酶羥脂酰輔酶A A脫氫酶脫氫酶酮脂酰輔酶酮脂酰輔酶A AOxidation硫解酶硫解酶脂酰輔酶脂酰輔酶A A乙酰轉(zhuǎn)移酶乙酰轉(zhuǎn)移酶豆蔻酰輔酶豆蔻酰輔酶A A(C14)乙酰輔酶乙酰輔酶A AThiolysis MultistepC16 ( Palmitoyl-CoA )C16 ( Palmitoyl-CoA )Oxidation of Fatty Acids棕櫚酰輔酶棕櫚酰輔酶A

27、豆蔻酰輔酶豆蔻酰輔酶A烯脂酰輔酶烯脂酰輔酶A A異構(gòu)酶異構(gòu)酶單不飽和脂肪酸單不飽和脂肪酸Oxidation of Unsaturated Fatty Acids Requires Two Additional Reactions烯脂酰輔酶烯脂酰輔酶A A異構(gòu)酶異構(gòu)酶單不飽和脂肪酸單不飽和脂肪酸Oxidation of Unsaturated Fatty Acids Requires Two Additional Reactionsoleate: 油酸; oleoyl: 油酰; dodecenoyl: 十二烯酰烯脂酰輔酶烯脂酰輔酶A A異構(gòu)酶異構(gòu)酶多不飽和脂肪酸多不飽和脂肪酸linoleate:

28、 亞油酸; linoleoyl: 亞油酰2,4-2,4-二烯脂酰輔酶二烯脂酰輔酶A A還原酶還原酶烯脂酰輔酶烯脂酰輔酶A A異構(gòu)酶異構(gòu)酶烯脂酰輔酶烯脂酰輔酶A A異構(gòu)酶異構(gòu)酶多不飽和脂肪酸多不飽和脂肪酸Complete Oxidation of Odd-Number (奇數(shù)奇數(shù)) Fatty Acids Requires Three Extra Reactionspropionyl: 丙酰; 丙酰輔酶丙酰輔酶A A羧化酶羧化酶甲基丙二酸單酰輔酶甲基丙二酸單酰輔酶A A差向異構(gòu)酶差向異構(gòu)酶D-D-甲基丙二酸單酰輔酶甲基丙二酸單酰輔酶A A 108- 2 (PPi) = 106Energy yie

29、ld:肉堿脂酰轉(zhuǎn)移酶肉堿脂酰轉(zhuǎn)移酶 I肉堿脂酰轉(zhuǎn)移酶肉堿脂酰轉(zhuǎn)移酶 I丙二酸單酰輔酶丙二酸單酰輔酶A丙二酸單酰輔酶丙二酸單酰輔酶AFatty Acid Oxidation Is Tightly Regulated硫解酶硫解酶脂酰輔酶脂酰輔酶A乙酰轉(zhuǎn)移酶乙酰轉(zhuǎn)移酶豆蔻酰輔酶豆蔻酰輔酶A乙酰輔酶乙酰輔酶A羥脂酰輔酶羥脂酰輔酶A脫氫酶脫氫酶酮脂酰輔酶酮脂酰輔酶AFeedback regulation of products(酮體酮體)丙酮丙酮乙酰乙酸乙酰乙酸羥基丁酸羥基丁酸硫解酶CO2 CoASH CoASH NAD+ NADH+H+ -羥丁酸羥丁酸脫氫酶脫氫酶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羥羥甲甲基基戊戊二二酸酸單單酰酰羥羥甲甲基基戊戊二二酸酸單單酰酰CoACoA= =OO= =OOHOCCHHOCCH2 2CCHCCH2 2CSCoACSCoA( (HMGCoAHMGCoA) ) CHCH3 3OHOH羥羥甲甲基基戊戊二二酸酸單單酰酰羥羥甲甲基基戊戊二二酸酸單單酰酰CoACoA= =OO= =OO= =OO= =OOCHCH3 3CHCHCHCH2 2COOH COOH D(D(- -) )- - - -羥羥丁丁酸酸羥羥丁丁酸酸OHOHCHCH3 3CHCHCHCH2 2COOH COOH D(D(- -) )-

32、 - - -羥羥丁丁酸酸羥羥丁丁酸酸CHCH3 3CHCHCHCH2 2COOH COOH D(D(- -) )- - - -羥羥丁丁酸酸羥羥丁丁酸酸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.丙二酸單酰輔酶丙二酸單酰輔酶A 22:14:2696基質(zhì)基質(zhì)細胞質(zhì)細胞質(zhì)檸檬酸檸檬酸檸檬酸合酶檸檬酸合酶草酰乙酸草酰乙酸蘋果酸蘋果酸丙酮酸丙酮酸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轉(zhuǎn)羧酶轉(zhuǎn)羧酶轉(zhuǎn)羧酶轉(zhuǎn)羧酶生物素羧化酶生物素羧化酶丙二酸單酰丙二酸單酰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-磷酸磷酸泛酰泛酰巰基巰基乙胺乙胺Acyl carrier protein (ACP, 酰基載體蛋白?；d體蛋白)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: 化學(xué)計算（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 (還原酶還原酶)Desaturase(去飽和酶去飽和酶) 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乙酰輔酶乙酰輔酶A丙二酸單酰輔酶丙二酸單酰輔酶ARegulation of fatty acid synthesis丙二酸單酰輔酶丙二酸單酰輔酶A22:14:32133Continued Lipid Metabolism22:1

41、4:32134K4 TriacylglycerolsMany Foods Contain Triacylglycerols豚鼠脂肪細胞22:14:33140 Lipoproteins: Triacylglycerols are transported round the body in large lipid-protein particles lipoproteins. 豚鼠脂肪細胞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: （兩部分組成的事物的）一部分22:14:33145l

43、ipin (lipid): 脂質(zhì)，脂類; perilipin: 外周脂質(zhì)脂肪動員(是指儲存在脂肪細胞中的脂是指儲存在脂肪細胞中的脂肪，被肪脂酶逐步水解為肪，被肪脂酶逐步水解為FFA及及甘油甘油并釋放入血以供其他并釋放入血以供其他組織氧化利用的過程。組織氧化利用的過程。)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: 磷酸二羥丙酮 (DHAP)Glyceroneogenesis22:14:35158Regulation of glyceroneogenesisFutile CycleHSLGlyceroneogenesis is regulated reciprocally in the liver and adipose tissue, affecting lipid m