生化脂代谢.ppt

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,2021,*,10.1 概述,脂类物质是生物体维持正常生命现象不可缺少,的.脂类包括的范围很广,脂类在化学结构、理化性质方面存在很大差异,但有共同点:不溶于水而溶于非极性有机溶剂,定义:,能被生物体利用,不溶于水,易溶于脂溶性溶剂的生物分子,生,物,功,能,生物膜的主要成分,储能物质,(1g糖或Pr17kJ 1g lip38kJ),保护、御寒功能,促进脂溶性物质的吸收,1,2021,分类,类脂,脂类,脂酸醇,复(合)脂:,脂类的水解产物:脂肪酸,萜,甾,脂肪,油,蜡,单(纯)脂:,脂酸醇非脂性物质,(糖/磷酸/氮碱/蛋白质),存在,形式,体质脂形式:作为原生质体存于细胞内,贮藏脂形式:贮于皮下等,2,2021,组成,脂肪(三酰甘油),CH,2,O-CO-R,1,CHO-CO-R,2,CH,2,O-CO-R,3,R,1,COOH,R,2,COOH +,R,3,COOH,脂酸,偶碳(C,4,C,28,),饱和/不饱和R,1,/R,2,/R,3,可相同也可不同,软脂酸C,16:0,硬脂酸C,18:0,油酸C,18:1,9,亚油酸C,18:2,9,12,亚麻酸C,18:3,9,12,15,CH,2,OH,CHOH ,CH,2,OH,甘油,c(顺),t(反),3,2021,磷脂,CH,2,O-CO-R,1,CHO-CO-R,2,CH,2,O-P-O-,X,+,O,O,胆碱:,HO-CH,2,CH,2,N,+,(CH),3,胆胺:,HO-CH,2,CH,2,N,+,H,3,丝氨酸:,HO-CH,2,CH(NH,2,)COOH,肌醇:,环己六醇,10.2 脂类的酶促降解,脂肪 二酰甘油 单酰甘油 甘油,脂酶,脂酶,脂酶,H,2,O 脂酸,H,2,O 脂酸,H,2,O 脂酸,4,2021,CH,2,O-CO-R,1,R,2,-CO-OCH,CH,2,O-P-O-,X,+,O,O,磷脂酶A,1,磷脂酶A,2,磷脂酶D,磷脂酶C,磷脂,5,2021,CH,2,O-CO-R,1,R,2,-CO-OCH,CH,2,O-P-O-,X,+,O,O,磷脂酶A,2,CH,2,O-CO-R,1,HO-CH,CH,2,O-P-O-,X,+,O,O,溶血磷脂,CH,2,-OH,HO-CH,CH,2,O-P-O-,X,+,O,O,无毒,蛇毒蜂毒蝎毒,6,2021,(CH,2,),n,-CH,3,-,-,C=O,胆固醇酯,胆固醇酯酶,7,2021,甘油三酯的消化与吸收,8,2021,10.3 脂肪的分解代谢,一.甘油的分解(胞浆中进行),CH,2,OH,CHOH,CH,2,OH,CH,2,OH,CHOH,CH,2,O-P,甘油,甘油-3-P,二羟丙酮-P,CH,2,OH,C=O,CH,2,-P,ATP ADP,NAD NADH,2,甘油-P-脱氢酶,甘油激酶M,g,2+,丙酮酸,G,酵解,异生,9,2021,1mol甘油分解为CO,2,+H,2,O,产生多少ATP?,甘油,甘油酸-1,3-2P,乙酰C,O,A,10ATP,NADH,2,ATP,ATP,NADH,2,NADH,2,ATP,18.5 ATP,甘油-3-P,二羟丙酮-P,甘油酸-3-P,丙酮酸,CO,2,+H,2,O,10,2021,二.脂肪酸的分解,-,-,-分解(氧化),-氧化1904年,F.Knoop实验证实,用奇碳、偶碳的苯脂酸饲养动物,收集尿液分析,11,2021,1.,-氧化,脂酸,活化,-氧化,胞浆,线粒体,a.反应历程,RCH,2,CH,2,CH,2,COOH,硫激酶,M,g,2+,ATP AMP,+,HSC,o,A PP,i,活化,脂酸,脂酰C,o,A,脂酰C,o,A,转运,脂酰C,o,A,乙酰C,o,A,RCH,2,CH,2,CH,2,COSC,o,A,12,2021,转运,RCH,2,CH,2,CH,2,COSC,o,A,RCH,2,CH,2,CH,2,COSC,o,A,转运,肉毒碱,脂酰肉毒碱,HSC,o,A,HSC,o,A,RCH,2,CH,2,CH,2,CO,SC,o,A,H,SC,o,A,(CH,3,),3,N,+,CH,2,CHCH,2,C-O,-,O,OH,(CH,3,),3,N,+,CH,2,CHCH,2,C-O,-,RCH,2,CH,2,CH,2,C=O,O,O,脂酰肉毒碱,肉毒碱,脂酰C,o,A,脂酰C,o,A,脂酰C,o,A,转移酶,转移酶,13,2021,转移酶,14,2021,-氧化,RCH,2,C,H,2,C,H,2,COSC,o,A,脂酰C,o,A,反-,-烯脂酰C,o,A,-羟脂酰C,o,A,RCH,2,C=CCOSC,o,A,H,H,-酮脂酰C,o,A,RCH,2,COSC,o,A,脂酰C,o,A(少2C),FAD FADH,2,脱氢酶,脱氢酶,水化酶,RCH,2,CHC,H,2,COSC,o,A,OH,H,2,O,NAD NADH,2,RCH,2,CCH,2,COSC,o,A,O,HSC,o,A,CH,3,COSC,o,A,硫解酶,TCA,循环,15,2021,特点,-位脱氢,-位加OH,-位加H,-位脱H,-位裂解,-氧化,b.能量,活化,脱氢,脱氢,以软脂酸(C,16:0,)为例计算能量,FADFADH,2,+1.5ATP,NADNADH,2,+2.5ATP,-氧化一轮+4ATP,ATPAMP+PP,i,-2ATP,C,16:0,C,14:0,C,12:0,2C+2C,(n/2 1)次循环,2P,i,16,2021,生成8mol CH,3,COSC,o,A,活化,-氧化,TCA循环,-2ATP,(n/2 1)次循环 7,4 +28ATP,8,10 +80ATP,+106ATP,CH,3,(CH,2,),14,COOH+ATP+7FAD+7H,2,O+8HSC,o,A+7NAD,+,总反应,8CH,3,COSC,o,A+AMP+PP,i,+7FADH,2,+7NADH,2,储能,30.52,1069790.56=0.33=33%,17,2021,c.奇数碳脂肪酸的,-氧化,奇碳脂酸,5C3C+2C,CH,3,CH,2,COSC,o,A+CH,3,COSC,o,A,丙酰C,o,A,乙酰C,o,A,丙酰C,o,A,琥珀酰C,o,ATCA,丙二酰C,o,A乙酰C,o,A TCA,CO,2,动物,植物,d.不饱和脂肪酸的,-氧化,以油酸(C,18:1,9,)为例,CH,3,(CH,2,),7,CH=CH(CH,2,),7,COOH,活化转运,CH,3,(CH,2,),7,CH=CH(CH,2,),7,COSC,o,A,18,2021,CH,3,(CH,2,),7,CH=CH(CH,2,),7,COSC,o,A,-氧化,16C,14C,12C(3次循环),CH,3,(CH,2,),7,CH=CHCH,2,COSC,o,A,顺-,-烯脂酰C,o,A,CH,3,(CH,2,),7,CH,2,C=CCOSC,o,A,反-,-烯脂酰C,o,A,H,H,异构酶,-氧化,2C5+2C,5次循环,能量,少1次脱氢(少得1mol FADH,2,),2C3,19,2021,能计算,4,(n/2-1),+,10,(n/2),1.5,双键数,-2,活化,-氧化次数,乙酰C,o,A分子数,2.,-氧化,RCH,2,COOH,R,COOH,单加氧酶,CO,2,2H,O,2,少1C羧酸,3.,-氧化,CH,3,(CH,2,),n,COOHHOCH,2,(CH,2,),n,COOH,HOOC(CH,2,),n,COOH,-氧化,末端甲基(,-端)氧化,-C氧化,O,H,RC,H,COOH,O,RCCOOH,O,2,单加氧酶,-氧化,20,2021,4.酮体的生成和利用,A.酮体的生成,-羟丁酸 CH,3,CH(OH)CH,2,COOH,脂酸,-氧化乙酰C,o,A,肝外组织,肝内组织,氧化不完全,乙酰乙酸CH,3,COCH,2,COOH,丙酮CH,3,COCH,3,酮体,TCA,酮体,21,2021,CO,2,CoASH,CoASH,NAD,+,NADH+H,+,-羟丁酸,脱氢酶,HMGCoA,合酶,乙酰乙酰CoA硫解酶,HMGCoA,裂解酶,22,2021,乙酰乙酰CoA还原酶,NADPH+H,+,NADP,+,CH,3,CHCH,2,CSCoA,OH,O,=,(,-羟丁酰CoA),-丁酰CoA,脱酰基酶,H,2,O,HSCoA,饥饿或糖尿病,23,2021,NAD,+,NADH+H,+,琥珀酰CoA,琥珀酸,CoASH+ATP,PPi+AMP,CoASH,琥珀酰CoA转硫酶,（心、肾、脑及骨骼肌的线粒体）,乙酰乙酰CoA硫激酶,（肾、心和脑的线粒体）,乙酰乙酰CoA硫解酶,（心、肾、脑及骨骼肌线粒体）,B.酮体的利用,24,2021,丙酮去路,a.随尿排出,b.直接从肺部呼出,c.转变为丙酮酸或甲酰基及乙酰基,酮体在肝脏合成,肝外分解,正常情况下,血液中酮体浓度相对恒定,饥饿/膳食中糖供给不足/糖尿病脂肪动员加速肝脏中酮体生成增加,糖代谢减少,丙酮酸缺乏,可与乙酰C,o,A缩合成柠檬酸的草酰乙酸,酮体去路,酮血症酸中毒,25,2021,10.4 脂肪的合成代谢,一.甘油的合成,G二羟丙酮-P 甘油-,-P,EMP,甘油-,-P脱氢酶,NADH,2,NAD,+,或,甘油 甘油-,-P,甘油-P激酶,ATP ADP,二.脂肪酸的合成,合成部位:胞浆(主要),线粒体/微粒体/叶绿体,26,2021,原料,:,乙酰CoA、NADPH,2,乙酰CoA(线粒体),胞浆,丙酮酸,甘油,乳酸,G,AA,脂酸,1.从头合成,非线粒体酶系合成,丙二酰C,o,A途径,乙酰C,o,A转运,27,2021,线,粒,体,膜,胞液,线粒体基质,丙酮酸,丙酮酸,苹果酸,草酰乙酸,柠檬酸,柠檬酸,乙酰CoA,NADPH+H,+,NADP,+,苹果酸酶,CoA,乙酰CoA,ATP,ADP Pi,柠檬酸裂解酶,CoA,草酰乙酸,H,2,O,柠檬酸合成酶,苹果酸,CO,2,CO,2,柠檬酸丙酮酸穿梭,28,2021,柠,檬,酸,柠,檬,酸,CH,3,CSC,o,A,O,CH,3,CSC,o,A,O,柠檬酸,合成酶,柠檬酸,裂解酶,草酰乙酸+H,2,O,HSC,o,A,草酰乙酸,+ADP+P,i,HSC,o,A,+ATP,丙二酸单酰C,o,A的合成,乙酰C,o,A羧化酶,M,g,2+,V,H,CO,2,+H,2,O+ATP,ADP+P,i,+H,+,HOOCCH,2,CSC,o,A,O,CH,3,CSC,o,A,O,丙二酸单酰CoA,29,2021,脂酸碳链的迭加,脂酸合,成酶系,酰基载体蛋白(ACP,ACPSH),六种酶,脂酰基转移酶E,1,丙二酰基转移酶E,2,-酮脂酰-ACP合成酶E,3,-酮脂酰-ACP还原酶E,4,-羟脂酰-ACP脱水酶E,5,-烯脂酰-ACP还原酶E,6,分子量40万,30,2021,-氧化:脱氢水合脱氢硫解,合成:缩合还原脱水还原,原始反应:,ACP-SH,HSC,o,A,E,2,ACP-SH,HSC,o,A,E,1,丙二酸单酰-S-ACP,乙酰-S-ACP,O,HOOCCH,2,CS,C,o,A,CH,3,CS,ACP,O,CH,3,CS,C,o,A,O,O,HOOCCH,2,CS,ACP,丙二酸单酰CoA,31,2021,CH,3,CS,ACP,O,O,H,OOC,CH,2,CS,ACP,+,CO,2,+ACPSH,E,3,CH,3,CCH,2,CS,ACP,O,O,乙酰乙酰-S-ACP,E,4,NADPH,2,NADP,CH,3,C,H,CH,2,CS,ACP,O,O,H,-羟丁酰-S-ACP,反-,-烯丁酰-S-ACP,E,5,H,2,O,E,6,NADPH,2,NADP,CH,3,CCCS,ACP,H,H,O,CH,3,CH,2,CH,2,CS,ACP,O,丁酰-S-ACP,循环,增,C,2,乙酰-S-ACP,丙二酸单酰-S-ACP,32,2021,循环,增,C,2,即,缩合,还原,脱水,还原,脂酰,ACP,硫酰酶,ACP-SH,H,2,O,脂酸,CH,3,CS,ACP,O,O,H,OOC,CH,2,CS,ACP,如:软脂酸(C,16:0,)的合成,需:循环7次,CH,3,CS,C,o,A,O,O,H,OOC,CH,2,CS,C,o,A,1mol,7mol,33,2021,总反应,CH,3,CSC,o,A,O,O,7HOOCCH,2,CSC,o,A,+7CO,2,+7H,2,O+7ATP,7CH,3,CSC,o,A,O,+7ADP+7P,i,O,+7HOOCCH,2,CSC,o,A,+14NADPH,2,CH,3,(CH,2,),14,COOH+14NADP+7CO,2,+8HSC,o,A+6H,2,O,8CH,3,CSC,o,A,O,+H,2,O+7ATP+14NADPH,2,CH,3,(CH,2,),14,COOH+7ADP+7P,i,+14NADP+8HSC,o,A,34,2021,ACP,乙酰CoA,乙酰基,HSCoA,丙二酰CoA,丙酰基,乙酰基,乙酰基,乙酰基,b,-酮脂酰基,CO,2,NADPH,NADP,+,b,-羟脂酰基,H,2,O,反式-,D,2,-烯脂酰基,NADPH,NADP,+,脂酰基,脂酰CoA,FFA,HSCoA,HSCoA,HSCoA,中央巯基,外围巯基,脂酰基转移酶,丙二酰基转移酶,b,-酮脂酰-ACP合成酶,b,-酮脂酰-ACP还原酶,b,-羟脂酰-ACP脱水酶,b-,烯脂酰-ACP还原酶,脂酸,合成酶,35,2021,36,2021,*,除酵母菌主要产生硬脂酸(C,18:0,)外,大多数机体脂酸合成到16C为止,可能因为,-酮脂酰-ACP合成酶只能接受14C的脂酰基,而不能接受大于14C的脂酰基的缘故,2.线粒体(微粒体)中的合成,脂酸碳链延长的合成,CH,3,CSC,o,A,O,软脂酰,C,o,A,延长,C链,(24C),从头合成,逆,-氧化,软脂酰,C,o,A(16C)+,CH,3,CSC,o,A,O,缩合,(18C),还原,硬脂酰,C,o,A(18C),还原,脱水,37,2021,3.奇碳饱和脂酸合成,起始为丙二酰,C,o,A,4.不饱和脂酸合成,不饱和键通过脂酰,C,o,A加氧酶催化形成,必须脂酸:亚油酸,(18:2,9,12,),亚麻酸,(18:2,9,12,15,),三.脂肪的合成,R,1,COSC,o,A,R,2,COSC,o,A,转酰酶,2HSC,o,A,CH,2,OH,CHOH +,CH,2,O-P,CH,2,O-COR,1,CHO-COR,2,CH,2,O-P,脂酰C,o,A,甘油-,-P,L-,-磷脂酸,38,2021,CH,2,O-COR,1,CHO-COR,2,CH,2,O-P,R,3,COSC,o,A,L-,-磷脂酸,磷酸酶,CH,2,O-COR,1,CHO-COR,2,CH,2,OH,甘油二酯,H,2,O P,i,甘油二酯转酰基酶,HSC,o,A,CH,2,O-COR,1,CHO-COR,2,CH,2,O-COR,3,脂肪,39,2021,CH,2,O-CO-R,1,R,2,-CO-OCH,CH,2,O-P-O-,X,+,O,O,磷脂酶A,1,(B,1,),磷脂酶A,2,(B,2,),磷脂酶D,磷脂酶C,10.5 磷脂的代谢,磷脂的分解,40,2021,磷脂的合成,甘油二酯,CDP-X,转移酶,CDP-X CMP,CH,2,O-COR,1,CHO-COR,2,CH,2,OH,CH,2,O-CO-R,1,R,2,-CO-OCH,CH,2,O-P-O-X,+,O,O,磷脂酸,CDP-甘油二酯,磷脂酰Ser,磷脂酰胆胺,磷脂酰胆碱,CH,2,O-COR,1,CHO-COR,2,CH,2,O-,CDP,CTP-X PP,i,Ser CMP,CO,2,CH,3,CH,2,O-COR,1,CHO-COR,2,CH,2,O-P,41,2021,CDP-X的合成,HO(CH,2,),2,N,+,H,3,HO(CH,2,),2,N,+,(CH,3,),3,HOCH,2,CHCOOH,NH,2,CDP-Ser,CDP-胆碱,CDP-胆胺,Ser,激酶,ATP,ADP,胆胺,激酶,ATP,ADP,胆碱,激酶,ATP,ADP,磷酰胆胺,转胞苷酶,CTP,PP,i,磷酰Ser,转胞苷酶,CTP,PP,i,磷酰胆碱,转胞苷酶,CTP,PP,i,CO,2,CH,3,P-CH,2,CHCOOH,NH,2,P-(CH,2,),2,N,+,(CH,3,),3,P-(CH,2,),2,N,+,H,3,42,2021,10.6 胆固醇代谢,1.胆固醇的转化,转变为,非开环,的各种衍生物,进一步被利用,并非彻底氧化分解,胆固醇,类固醇,进一步利用,排出体外,排出体外,少量,少量,性激素,胆汁酸,V,D,肾上腺皮质激素,43,2021,2.胆固醇的合成,(胞浆/微粒体),胆固醇(27C),原料:乙酰C,o,A,a.乙酰C,o,A+乙酰乙酰C,o,A,-羟-甲戊二酸(6C),b.脱羧异戊二烯单位(5C),c.6个异戊二烯单位缩合鲨烯(30C),d.羊毛脂固醇(30C),e.胆固醇(27C),44,2021,45,2021,46,2021,