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1、Metabolism of lipidsCourse ContentDigestion and absorption of lipidsplasma lipoprotein metabolismTriacylglycerol metabolismPhospholipid metabolismCholesterol metabolism目的要求：目的要求：1、掌握掌握血浆脂蛋白的分类、组成及功能，血浆脂蛋白的分类、组成及功能，甘油三酯的分解代谢及胆固醇的转化。甘油三酯的分解代谢及胆固醇的转化。2、熟悉熟悉脂类的分类脂类的分类,甘油三酯、胆固醇的合甘油三酯、胆固醇的合成。成。3、了解了解磷脂代谢磷
2、脂代谢,多不饱和脂肪酸的重要衍多不饱和脂肪酸的重要衍生物。脂类代谢紊乱与疾病关系生物。脂类代谢紊乱与疾病关系第一节第一节 脂类的分布和生理功能脂类的分布和生理功能一、脂类分布一、脂类分布 甘油三酯（三酰甘油、脂肪）：真脂、储存脂、可变脂甘油三酯（三酰甘油、脂肪）：真脂、储存脂、可变脂 皮下、腹腔大网膜、肠系膜、内脏周围皮下、腹腔大网膜、肠系膜、内脏周围脂库脂库 类脂：类脂：基本脂、固定脂基本脂、固定脂 生物膜、神经组织生物膜、神经组织二、脂类的生理功能二、脂类的生理功能（一）三酰甘油的生理功能：（一）三酰甘油的生理功能：1、是一种能源物质，储能和氧化供能、是一种能源物质，储能和氧化供能 2、提
3、供、提供必需脂肪酸必需脂肪酸essential fatty acids 3、溶解脂溶性维生素、溶解脂溶性维生素（二）类脂功能：（二）类脂功能：1、是生物膜的组成成分、是生物膜的组成成分cell membrane components 膜的流动性和坚固性与脂类有关膜的流动性和坚固性与脂类有关 2、协助脂类及脂溶性维生素的吸收和运输、协助脂类及脂溶性维生素的吸收和运输 absorption and transportation of fat-soluble vitamins 3、胆固醇是合成、胆固醇是合成vitaminD3、胆汁酸、胆汁酸bile acid和各种类固和各种类固醇激素醇激素stero
4、id hormones等物质的原料等物质的原料一一、脂类消化、脂类消化(digestion)：酯键水解酯键水解消化部位：小肠消化部位：小肠(small intestine)消化酶：消化酶：胰脂酶胰脂酶(steapsin,pancreatic lipase)胰磷脂酶胰磷脂酶(pancreatic phosphatidase)胆固醇酯酶胆固醇酯酶(cholesterase)等等二、脂类吸收二、脂类吸收(absorption)植物固醇不吸收、抑制胆固醇的吸收植物固醇不吸收、抑制胆固醇的吸收胆汁酸促进脂类消化吸收胆汁酸促进脂类消化吸收消化产物：脂肪酸、单酰甘油（消化产物：脂肪酸、单酰甘油（monoac
5、ylglycerol ）溶血磷脂溶血磷脂(lysophosphatide)、胆固醇、胆固醇第二节第二节 脂类的消化和吸收脂类的消化和吸收小肠上段小肠上段是主要的消化场所是主要的消化场所脂类脂类(TG(TG、ChCh、PLPL等等)微团微团胆汁酸盐胆汁酸盐乳化乳化胰脂肪酶、辅脂酶等水解胰脂肪酶、辅脂酶等水解甘油一脂、溶血磷脂、甘油一脂、溶血磷脂、长链脂肪酸、胆固醇等长链脂肪酸、胆固醇等混合微团混合微团乳化乳化脂类的吸收脂类的吸收在在十二指肠下段十二指肠下段及及空肠上段空肠上段吸收吸收混合混合微团微团扩散扩散小肠粘膜小肠粘膜细胞内细胞内重新酯化重新酯化载脂蛋白结合载脂蛋白结合乳糜微粒乳糜微粒门静脉
6、门静脉肝脏肝脏Digestion of Triacylglycerols一、血脂的组成与含量一、血脂的组成与含量(blood fat,plasma lipids)（一）概念：血浆中所含的脂类。（一）概念：血浆中所含的脂类。（二）主要成分：（二）主要成分：三酰甘油三酰甘油(triacylglycerol)磷脂磷脂(phospholipid)胆固醇和胆固醇酯胆固醇和胆固醇酯(cholesterol and cholesterol ester)游离脂肪酸游离脂肪酸(free fatty acid)（三）血脂含量：不稳定（三）血脂含量：不稳定第三节第三节 血脂血脂plasma lipids（二）血脂的
7、来源和去路（二）血脂的来源和去路构成生物膜构成生物膜转变为其它物质转变为其它物质食物食物体内合成体内合成脂库动员脂库动员氧化供能氧化供能脂脂库库储存储存血脂血脂CM脂肪酸脂肪酸-清蛋白清蛋白 VLDL三、血浆脂蛋白三、血浆脂蛋白(lipoprotein)（血脂的运输形式）（血脂的运输形式）成分：脂类、蛋白质（载脂蛋白）成分：脂类、蛋白质（载脂蛋白）（一）血浆脂蛋白的分类与命名（一）血浆脂蛋白的分类与命名 1、电泳、电泳(electrophoresis)分类法：分类法：-脂蛋白、前脂蛋白、前-脂蛋白脂蛋白pre-、-脂蛋白、脂蛋白、乳糜微粒乳糜微粒(chylomicron,CM）2、超速离心、超
8、速离心(ultracentrifugation)分类法：分类法：CM、VLDL、LDL、HDL（一）电泳法（一）电泳法electrophoresis按其移动的快慢，可将脂蛋白依次分为：按其移动的快慢，可将脂蛋白依次分为：-脂蛋白、脂蛋白、前前-脂蛋白、脂蛋白、-脂蛋白，乳糜微粒脂蛋白，乳糜微粒chylomicron在原点不动在原点不动+CM 前前 血浆脂蛋白琼脂糖凝胶电泳图谱血浆脂蛋白琼脂糖凝胶电泳图谱（二）超速离心法（二）超速离心法按密度大小依次为：按密度大小依次为：密密度度颗颗粒粒乳糜微粒乳糜微粒（CMCM）极低密度脂蛋白极低密度脂蛋白（VLDL)低密度脂蛋白低密度脂蛋白 (LDL)高密度
9、脂蛋白高密度脂蛋白(HDL）HDL又可分为又可分为HDL1、HDL2、HDL3等亚类。等亚类。尚有脂蛋白尚有脂蛋白(a)LP(a)。游离脂肪酸游离脂肪酸(FFA)与清蛋白结合而运输与清蛋白结合而运输.3 3、电泳分类法与超速离心法的对应关系、电泳分类法与超速离心法的对应关系（三）、血浆脂蛋白的结构特点：（三）、血浆脂蛋白的结构特点：以非极性脂（如：三酰甘油）为核心，表面覆盖以单层极以非极性脂（如：三酰甘油）为核心，表面覆盖以单层极 性分子（如：磷脂、载脂蛋白及游离的胆固醇等）。性分子（如：磷脂、载脂蛋白及游离的胆固醇等）。电泳分类法电泳分类法 超速离心分类法超速离心分类法小小 小小 CM CM
10、 VLDL 前前-LDL HDL迁迁移移率率密密度度（二）、血浆脂蛋白的组成（二）、血浆脂蛋白的组成 蛋白质（载脂蛋白蛋白质（载脂蛋白apolipoprotein,apoprotein)血浆脂蛋白血浆脂蛋白 脂类（三酰甘油、胆固醇及其酯、磷脂脂类（三酰甘油、胆固醇及其酯、磷脂）外周载脂蛋白外周载脂蛋白Peripheral apoprotein磷脂磷脂Phospholipid三酰甘油三酰甘油Triacylglycerol胆固醇酯胆固醇酯Cholesterol ester非极性脂类核心非极性脂类核心Core of mainly nonpolar lipids游离胆固醇游离胆固醇Free chole
11、sterol整合的载脂蛋白整合的载脂蛋白Integral apoprotein血浆脂蛋白的结构特点：血浆脂蛋白的结构特点：以非极性脂以非极性脂nonpolar lipids为核心，表面覆盖以单层极性分子为核心，表面覆盖以单层极性分子polar molecule，组成球状颗粒。组成球状颗粒。载脂蛋白载脂蛋白(apolipoprotein,Apo)：血浆脂蛋白中的蛋白质部分。血浆脂蛋白中的蛋白质部分。Apo至少有至少有18种，分为种，分为ApoA(A1、A)、(B100、B48)、C(C1、C、C)、D、E、F、J及及Apo(a)。功能：功能：(1)结合和转运脂类；结合和转运脂类；(2)调节酶活性
12、调节酶活性；(3)作为脂蛋白受体的配体。作为脂蛋白受体的配体。（四）血浆脂蛋白的代谢与功能（四）血浆脂蛋白的代谢与功能1、代谢、代谢乳糜微粒（乳糜微粒（CM）合成部位及来源合成部位及来源:小肠粘膜细胞内合成。转运小肠粘膜细胞内合成。转运 外源性脂类外源性脂类.主要代谢变化主要代谢变化:新生新生CM从从HDL获得获得ApoC、ApoE转变为成熟转变为成熟的的CM，C激活肝外毛细血管内皮细胞表面的激活肝外毛细血管内皮细胞表面的LPL，从而，从而使使CM中的中的TG反复水解（反复水解（90%以上），表面过多的以上），表面过多的ApoA、ApoC及磷脂、及磷脂、Ch转移给转移给HDL，并从，并从HDL
13、处接受处接受CE(胆固醇胆固醇酯酯)（CETP协助）。成为协助）。成为 富含富含ApoE 及及CE的的CM残粒。残粒。CM残粒可被残粒可被Apo E受体受体识别和摄取识别和摄取.清清除除方方式式:迅迅速速被被肝肝脏脏清清除除，一一半半通通过过LRP，另另一半则通过一半则通过ApoBE受体。受体。CM颗粒大能使光散射，密度小。饭后血清，颗粒大能使光散射，密度小。饭后血清，4过夜形成奶油层。过夜形成奶油层。P P ChChA AE ECCHDLHDLapo-E apo-E ReceptorReceptorTG TG ChChCCE EA AB48B48MatureMatureCMCMP.Ch ap
14、o-A.apo-C apo-E.apo-CDietary Dietary TGTG小小肠肠淋巴淋巴TG TG ChChA AB48B48Nascent CMNascent CMSmall Small IntestineIntestineLymphaticsLymphaticsCholesterolCholesterolFatty acidsFatty acidsLIVERLIVER脂蛋白脂酶脂蛋白脂酶fatty acidfatty acidLipoprotein Lipoprotein LipaseLipase肝外组织肝外组织GlycerolGlycerolExtrahepatic Extra
15、hepatic tissuestissuesTGTGChChapo-Eapo-EB48B48Rump Rump CMCM2）VLDL、IDL、LDL VLDL亦为较大颗粒，当血中水平升高时，血清外观呈乳浊，亦为较大颗粒，当血中水平升高时，血清外观呈乳浊，但但4过夜不形成奶油层。过夜不形成奶油层。Lipoprotein Lipoprotein LipaseLipaseExtrahepa-Extrahepa-tic tissuestic tissuesFatty Fatty acidsacidsGlycerolGlycerolP P ChChAE ECCHDLHDLTGCTGCh hapo-Cap
16、o-Capo-Eapo-Eapo-B100apo-B100MatureVLDLVLDLP.ChP.Ch.apo-C.apo-Capo-C apo-EB100B100TGTGChChapo-Eapo-EIDLIDLapo-Eapo-ETG TG ChChB100B100Nascent VLDLIntestineIntestineExtrahepatic Extrahepatic tissuestissues Fatty acids Fatty acidsCholesterolCholesterolapo-B apo-B、E E ReceptorReceptorChChapo-Bapo-B1001
17、00LDLLDL1、CM 含含TG90%，小肠黏膜细胞合成，新生，小肠黏膜细胞合成，新生CM 有有apoA、B-48，在血液中从，在血液中从HDL处获得处获得apoC、apoE成为成熟成为成熟CM，在肝，在肝降解。半衰期降解。半衰期5-15min.组成和代谢特点：组成和代谢特点：2、VLDL、IDL、LDL VLDL含含TG 60%，肝合成，新生，肝合成，新生VLDL 有有apoB100、apoE，在血液中从在血液中从HDL获得获得apoC、apoE成为成熟成为成熟VLDL。TG水解、水解、apoC移至移至HDL后形成后形成IDL，IDL的的TG继续被组织继续被组织LPL水解，水解，apoE移
18、至移至HDL，最后剩下，最后剩下胆固醇酯为主（胆固醇酯为主（50%）和和apoB100 即即形成了形成了LDL。LDL与肝或肝外中特异受体（与肝或肝外中特异受体（apoB100受体受体,apoBE受体）结合，放出受体）结合，放出Ch 利用或被肝降解。利用或被肝降解。3、HDL 含含C 20%，磷脂，磷脂25%，蛋白质，蛋白质50%。肝、小肠合成，有肝、小肠合成，有apoA、apoC、apoE，血浆血浆LCAT使新生使新生HDL的胆固醇酯化，成的胆固醇酯化，成为成熟为成熟HDL，在肝降解。，在肝降解。血浆脂蛋白的功能血浆脂蛋白的功能 血浆脂蛋白血浆脂蛋白 合合 成成功功 能能 C M代谢代谢小肠
19、小肠转运转运外源性脂类外源性脂类（三酰甘油为主）（三酰甘油为主）至全身至全身 VLDL代谢代谢 肝脏肝脏运输运输内源性脂类内源性脂类（三酰甘油为主）（三酰甘油为主）由肝至全身由肝至全身 LDL代谢代谢肝脏，血浆中肝脏，血浆中VLDL代谢而来代谢而来运输肝合成的内源性运输肝合成的内源性胆固醇胆固醇至全身至全身 HDL代谢代谢肝脏、小肠肝脏、小肠运输外周组织的运输外周组织的胆固醇胆固醇至肝脏（胆固醇的至肝脏（胆固醇的逆转运逆转运）一、一、甘油三酯的分解代谢甘油三酯的分解代谢 triacylglycerol catabolism第四节第四节 甘油三酯的中间代谢甘油三酯的中间代谢intermediar
20、y metabolism 甘油甘油 glycerol脂肪酸脂肪酸 fatty acid脂库三酰甘油脂库三酰甘油triacylglycerol脂肪酶脂肪酶（一）脂肪动员一）脂肪动员fat Mobilization 1、概念：、概念：2、关键酶、关键酶key enzyme：三酰甘油脂肪酶：三酰甘油脂肪酶 （激素敏感性脂肪酶（激素敏感性脂肪酶 hormone-sensitive lipase）脂解激素脂解激素抗脂解激素：胰岛素抗脂解激素：胰岛素insulin Mobilization of triacylglycerolsMobilization of triacylglycerols:in the
21、 adipose tissue,breaks down triacylglycerols to freefatty acids and glycerol(fattyacids are hydrolyzed initiallyfrom C1or C3 of the fat)hormone sensitive lipase cleave a fatty acid from atriglyceride,then other lipasecomplete the process of lipolysis,and fatty acid are released intothe blood by seru
22、m albumin脂肪脂肪组织组织贮存贮存的甘的甘油三油三酯的酯的动员动员 CH2OOCR1R2COOCH CH2OOCR3 CH2OHR2COOCH CH2OOCR3 CH2OHR2COOCH CH2OH脂肪酶脂肪酶脂肪酶脂肪酶脂肪酶脂肪酶 CH2OH HOCH CH2OH+RCOOH（二）甘油的氧化（二）甘油的氧化 CH2OH HOCH CH2OH甘油激酶甘油激酶 CH2OH HOCH CH2OPO3H2Pi甘油脱氢酶甘油脱氢酶 CH2OH O=C CH2OPO3H2 甘油甘油-甘油磷酸甘油磷酸二羟丙酮磷酸二羟丙酮磷酸(dihydroxy-acetone phosphate)dihydro
23、xy-acetone phosphate)糖代谢、糖代谢、糖异生途径糖异生途径glyconeogenesis(三）脂肪酸的氧化三）脂肪酸的氧化(Oxidation)氧化方式：氧化方式：氧化氧化、氧化、氧化、氧化等氧化等概念概念脂酰基（脂肪酸）在线粒体内的氧化分解是从脂酰基的脂酰基（脂肪酸）在线粒体内的氧化分解是从脂酰基的-碳原子开始，进行碳原子开始，进行脱氢、加水、再脱氢、硫解脱氢、加水、再脱氢、硫解产生乙酰产生乙酰CoA的的反应过程。反应过程。氧化过程氧化过程：（1）脂肪酸的活化脂酰）脂肪酸的活化脂酰CoA(acyl-CoA)的生成的生成 活化部位：胞液活化部位：胞液（2）脂酰）脂酰CoA进
24、入线粒体进入线粒体 载体载体:肉（毒）碱肉（毒）碱(carnitine)酶：肉（毒）碱脂酰转移酶酶：肉（毒）碱脂酰转移酶(carnitine acyl transferase)review Catabolism of TAG Mobilization of triacylglycerolsMobilization of triacylglycerols:in the adipose tissue,breaks down triacylglycerols to freefatty acids and glycerol(fattyacids are hydrolyzed initiallyfrom
25、 C1or C3 of the fat)hormone sensitive lipase(HSL)cleaves a fatty acid from atriglyceride,then other lipasescomplete the process of lipolysis,and fatty acid are released intothe blood by serum albumin清清蛋白蛋白.The glycerol is absorbed by the liver and converted to glycolytic intermediatesFatty acid bata
26、 oxidationMITOCHONDRIONcell membraneFA=fatty acidLPL=lipoprotein lipaseFABP=fatty acid binding proteinACSFABPFABPFA3FABPacyl-CoA4CYTOPLASMCAPILLARYLPL lipoproteins2FAFA1albuminFAFAFAFrom adipose cellcarnitinetransporteracyl-CoA5 Overview of fatty acid degradation ACS=acyl CoA synthetaseacetyl-CoATCA
27、cycle-oxidation67Acyl CoA synthetase reaction occurs on the mitochondrial membrane1.Activation of Fatty AcidsCarnitine肉毒碱肉毒碱 carries long-chain activated fatty acids into the mitochondrial matrix.2.Transport into Mitochondrial MatrixEach round in fatty acid degradation involves four reactions1.oxida
28、tion totrans-2-Enoly-CoARemoves H atoms from the and carbons-Forms a trans C=C bond-Reduces FAD to FADH23.Fatty acid Beta oxidation 2.Hydration to L3Hydroxylacyl CoAAdds water across the trans C=C bondForms a hydroxyl group(OH)on the carbon 3.Oxidation to3Ketoacyl CoAOxidizes the hydroxyl groupForms
29、 a keto group on the carbon 4.Thiolysis to produce AcetylCoAacetyl CoA is cleaved:By splitting the bond between the and carbons.To form a shortened fatty acyl CoA that repeats steps 1-4 of -oxidation-Oxidation of-Oxidation of Fatty Acid:Fatty Acid:、-enoyl CoA-enoyl CoA Acyl CoA Acyl CoA dehydrogenas
30、edehydrogenaseFADFADFADHFADH2 2Acyl CoAAcyl CoA（Rn-Rn-2 2）thiolasethiolaseSH-CoASH-CoAAcetyl CoAAcetyl CoA-ketoacyl CoA-ketoacyl CoANADNADNADH+HNADH+H+Hydroxyacyl CoA Hydroxyacyl CoA DehydrogenaseDehydrogenaseAcyl CoAAcyl CoA（RnRn）Fatty acidsFatty acids（RnRn）TCATCACCDehydrogenationHydrationDehydroge
31、nationThiolysis(Carbon-Carbon Cleavage)Carbon Backbone Reaction Sequence:-hydroxyacyl CoA-hydroxyacyl CoAEnoyl CoA hydrataseEnoyl CoA hydrataseH2OCycles of-OxidationThe length of a fatty acidDetermines the number of oxidations and the total number of acetyl CoA groups Carbons in Acetyl CoA -Oxidatio
32、n CyclesFatty Acid (C/2)(C/2 1)12 6 514 7 6168718 98-Oxidation and ATPActivation of a fatty acid requires:2 ATPOne cycle of oxidation of a fatty acid produces:1 NADH 3 ATP 1 FADH2 2 ATPAcetyl CoA entering the citric acid cycle produces:1 Acetyl CoA12 ATPATP for Myristic Acid肉豆蔻酸肉豆蔻酸 C14ATP productio
33、n for Myristic(14 carbons):Activation of myristic acid-2 ATP7 Acetyl CoA7 acetyl CoA x 12 ATP/acetyl CoA 84 ATP6 Oxidation cycles 6 NADH x 3ATP/NADH18 ATP6 FADH2 x 2ATP/FADH212 ATPTotal 102 ATPOxidation of Special Cases(monounsaturated fatty acids)Odd Carbon Fatty Acids5 Cycles5 CH3COSCoA +CH3CH2COS
34、CoAPropionyl丙酰丙酰CoAD-Methylmalonyl甲基丙二酰甲基丙二酰CoAL-MethylmalonylCoASuccinyl CoATCA CyclePropionyl CoA Carboxylase羧化酶羧化酶ATP/CO2EpimeraseMutaseVit.B12Ketogenesis酮体生成酮体生成:the formation of Ketone Bodies*2 CH3COSCoA CH3COCH2COSCoAThiolaseCH3COSCoAAcetoacetyl CoA乙酰乙酰辅酶乙酰乙酰辅酶AHOOC-CH2-C-CH2COSCoAOHCH3-Hydrox
35、y-methylglutaryl戊二酰戊二酰 CoA(HMG CoA)HMG CoASynthase合酶合酶Cholesterol(in cytosol)SeveralstepsKetogenesis(in liver:mitochon-drial matrix)HMG CoAHMG CoAKetogenesis:formation of Ketone BodiesHO2C-CH2-C-CH2COSCoAOHCH3HMG CoACH3COCH2CO2HAcetoacetic Acid乙酰乙酸乙酰乙酸HMG CoA lyaseHMG CoA lyase-CH3COSCoA-CO2CH3COCH3
36、Acetone(volatile挥发性的挥发性的)CH3CHCH2CO2HOH-Hydroxybutyrate羟基丁酸羟基丁酸NADH+H+NAD+DehydrogenaseKetone bodies are important sources of energy,especially in starvationAcetoacetate-Hydroxybutyrate-Hydroxybutyrate dehydrogenaseNAD+NADHCitricAcidCycle2 Acetyl CoACoAThiolaseAcetoacetyl CoASuccinyl CoASuccinateCoA
37、 transferaseOxidation of ketone bodies in brain,muscle,kidney,and intestineSuccinyl CoA synthetase=loss of GTPThe significance of ketogenesis and ketogenolysisKetone bodies are water soluble,they are convenient to transport in blood,and readily taken up by non-hepatic tissues.In the early stages of
38、fasting,the use of ketone bodies by heart,skeletal muscle conserves glucose for support of central nervous system.With more prolonged starvation,brain can take up more ketone bodies to spare glucose consumption High concentration of ketone bodies can induce ketonemia酮血症酮血症 and ketonuria酮酮尿尿,and even
39、 ketosis and acidosis酸中毒酸中毒 When carbohydrate碳水化合物碳水化合物 catabolism is blocked by a disease of diabetes mellitus糖尿病糖尿病 or defect of sugar source,the blood concentration of ketone bodies may increase,the patient may suffer from ketosis酮症酮症 and acidosisTCACOverview Catabolism of TAGglycerolKetone bodie
40、sFatty acid are synthesized and degraded by different pathways.from acetyl CoA-原料原料in the cytosol(肝肝、肾、脑、肺、乳腺、肾、脑、肺、乳腺、脂肪等脂肪等组织的组织的胞液胞液)intermediates are attached to the acyl carrier protein(ACP)the activated donor is malonyl丙二酰丙二酰ACPUses NADPH+H+as reductantstops at C16(palmitic acid 软脂酸软脂酸)Lipogen
41、esis脂肪生成脂肪生成:Fatty Acid Biosynthesis合成过程：合成过程：乙酰乙酰CoA从线粒体向胞液的转运：苹果从线粒体向胞液的转运：苹果酸酸柠檬酸穿梭系统柠檬酸穿梭系统(Malate-Citrate suttle)/柠檬酸穿梭系统柠檬酸穿梭系统(Citrate suttle）丙二酸单酰丙二酸单酰CoA(Malonyl-CoA)的形成的形成 软脂酸的合成过程软脂酸的合成过程AcetylCoA is synthesized in the mitochondrial matrix,whereas fatty acids are synthesized in the cytoso
42、lAcetylCoA units are shuttled out of the mitochondrial matrix as citrate:Citrate ShuttleFormation of malonylCoA is the committed step关键步骤关键步骤 in fatty acid synthesisFormation of Malonyl Coenzyme A O|CH3CSCoA +HCO3-+ATP Acetyl CoA O O|-OCCH2CSACP+ADP+PiMalonyl(丙二酰丙二酰)CoA乙酰乙酰CoA羧化酶羧化酶Acetyl CoA carbox
43、ylase高等动物中高等动物中:脂肪酸合成酶系：脂酰基载体蛋白（脂肪酸合成酶系：脂酰基载体蛋白（ACP)6种酶活性的多功能酶种酶活性的多功能酶:6种酶活性都在一条多肽链上，有三个结构域，种酶活性都在一条多肽链上，有三个结构域，属多功能酶，由一个基因编码；有活性的酶为属多功能酶，由一个基因编码；有活性的酶为两个相同亚基首尾相连组成的二聚体。两个相同亚基首尾相连组成的二聚体。辅基为辅基为4磷酸泛酰氨基乙硫醇。磷酸泛酰氨基乙硫醇。硫酯酶硫酯酶乙酰基转移酶乙酰基转移酶丙二酰基转移酶丙二酰基转移酶-酮脂酰合成酶酮脂酰合成酶-酮脂酰还原酶酮脂酰还原酶-羟酰脱水酶羟酰脱水酶-烯脂酰还原酶烯脂酰还原酶具体过程
44、具体过程Condensation缩合缩合 and Reduction In reactions 1 and 2 of fatty acid synthesis:Condensation by a synthase combines acetyl-ACP with malonyl-ACP to form acetoacetyl-ACP(4C)and CO2(reaction 1)Reduction converts a ketone to an alcohol by using NADPH(reaction 2)Dehydration and ReductionIn reactions 3 an
45、d 4 of fatty acid synthesis:Dehydration forms a trans double bond(reaction 3)Reduction converts the double bond to a single bond by using NADPH(Reaction 4)Lipogenesis Cycle Repeats Fatty acid synthesis continues:Malonyl-ACP combines with the four-carbon butyryl-ACP to form a six-carbon-ACP.The carbo
46、n chain lengthens by two carbons each cycleLipogenesis Cycle Completed Fatty acid synthesis is completed when palmitoyl棕榈酰棕榈酰 ACP reacts with water to give palmitate(C16)and free ACP.Summary of Lipogenesispalmitic acid biosynthesispalmitic acid biosynthesisMalonyl-CoAMalonyl-CoAAcetyl-CoAAcetyl-CoAc
47、arboxylasecarboxylaseCOCO2 27 7 Acetyl-CoAAcetyl-CoAAcetyl-CoAAcetyl-CoA7 7 7 7 Acetyl-CoAAcetyl-CoAFatty acid synthase Fatty acid synthase complexcomplexPalmitic acidPalmitic acid（16C16C）microsome mitochondriamitochondriaEndoplasmic reticulum(内质网内质网)systems introduce double bonds into long chain ac
48、ylCoAsReaction combines both NADH and the acylCoAs to reduce O2 to H2OElongation and Unsaturationconvert palmitoylCoA to other fatty acidsReactions occur on the cytosolic face of the endoplasmic reticulum.MalonylCoA is the donor in elongation reactions Oxidation and Fatty Acid SynthesisFatty Acid Fo
49、rmationShorter fatty acids undergo fewer cycles Longer fatty acids are produced from palmitate by using special enzymesUnsaturated不饱和的不饱和的 cis顺式顺式 bonds are incorporated into a 10-carbon fatty acid that is then elongated furtherWhen blood glucose is high,insulin胰岛素胰岛素 stimulates glycolysis and pyruv
50、ate oxidation to obtain acetyl CoA to form fatty acids.The stoichiometry of palmitate synthesis:Synthesis of palmitate from MalonylCoASynthesis of MalonylCoA from AcetylCoAOverall synthesisStoichiometry化学计量学化学计量学of FA synthesisThe malate dehydrogenase and NADP+linked malate enzyme reactions of the c