生物化学：第12章脂类代谢

1、 第十二章脂类代谢第十二章脂类代谢 （）（）20日日AFP時事】最高時時事】最高時体重体重 560記録（記録（41） ） 、記録登録分。、記録登録分。 、200減量達成人減量達成人記録記録 登録。登録。 AFP通信、記録最太人通信、記録最太人 登録。、登録。、200体重減体重減 幸語幸語。記録最体重。記録最体重 重人認定、重人認定、2008年版写真年版写真 載、治療過程紹介。載、治療過程紹介。 Key Terms triacylglycerol (neutral fat, triacylglyceride) bile salt chylomicron acyl adenylate carnit

2、ine b-oxidation pathway vitamin B12 (cobalamin) peroxisome ketone body acyl carrier protein (ACP) fatty acid synthase malonyl CoA acetyl CoA carboxylase megasynthase polyketide nonribosomal peptide AMP-dependent protein kinase (AMPK) protein phosphatase 2A arachidonate prostaglandin eicosanoid II. T

3、ransducing An Overview of Fatty Acid Metabolism Fatty acid degradation and synthesis are relatively simple processes that are essentially the reverse of each other. The process of degradation converts an aliphatic compound into a set of activated acetyl units (acetyl CoA) that can be processed by th

4、e citric acid cycle (Figure 22.2). An activated fatty acid is oxidized to introduce a double bond; the double bond is hydrated to introduce an oxygen; the alcohol is oxidized to a ketone; and, finally, the four carbon fragment is cleaved by coenzyme A to yield acetyl CoA and a fatty acid chain two c

5、arbons shorter. If the fatty acid has an even number of carbon atoms and is saturated, the process is simply repeated until the fatty acid is completely converted into acetyl CoA units. Fatty acid synthesis is essentially the reverse of this process. Because the result is a polymer, the process star

6、ts with monomers in this case with activated acyl group (most simply, an acetyl unit) and malonyl units (see Figure 22.2). The malonyl unit is condensed with the acetyl unit to form a four-carbon fragment. To produce the required hydrocarbon chain, the carbonyl must be reduced. The fragment is reduc

7、ed, dehydrated, and reduced again, exactly the opposite ofdegradation, to bring the carbonyl group to the level of a methylene group with the formation of butyryl CoA. Another activated malonyl group condenses with the butyryl unit and the process is repeated until a C16 fatty acid is synthesized Tr

8、iacylglycerols Are Highly Concentrated Energy Stores Fatty acids are physiologically important as (1) components of phospholipids and glycolipids, (2) hydrophilic modifiers of proteins, (3) fuel molecules, and (4) hormones and intracellular messengers. They are stored in adipose tissue as triacylgly

9、cerols (neutral fat). 一一 脂类的生理功能脂类的生理功能 构成细胞膜的必要成分构成细胞膜的必要成分 氧化供能：氧化供能： 9 9克葡萄糖克葡萄糖1 1克脂肪克脂肪？ 其他功能其他功能： 保持体温保持体温 保护，固定内脏保护，固定内脏 胆固醇是生成胆汁酸，胆固醇是生成胆汁酸，VD3VD3，类固醇激，类固醇激 素的原料素的原料 H H3 3C-C-（CHCH2 2）n-C-C-C=On-C-C-C=O - OHOH 脂肪酸的通式脂肪酸的通式： Triacylglycerols are highly concentrated stores of metabolic energy

10、 because they are reduced and anhydrous. The yield from the complete oxidation of fatty acids is about 9 kcal g-1 (38 kJ g-1), in contrast with about 4 kcal g-1 (17 kJ g-1) for carbohydrates and proteins. The basis of this large difference in calori yield is that fatty acids are much more reduced. F

11、urthermore, triacylglycerols are nonpolar, and so they are stored in a nearly anhydrous form, whereas much more polar proteins and carbohydrates are more highly hydrated. In fact, 1 g of dry glycogen binds about 2 g of water. Consequently, a gram of nearly anhydrous fat stores more than six times as

12、 much energy as a gram of hydratedglycogen, which is likely the reason that triacylglycerols rather than glycogen were selected in evolution as the major energy reservoir.The glycogen and glucose stores provide enough energy to sustain biological function for about 24 hours, whereas the triacylglyce

13、rol stores allow survival for several weeks. Triacylglycerols Are Highly Concentrated Energy Stores The utility of triacylglycerols as an energy source is dramatically illustrated by the abilities of migratory birds, which can fly great distances without eating. Examples are the American golden plov

14、er and the ruby-throated sparrow. The golden plover flies from Alaska to the southern tip of South America; a large segment of the flight (3800 km, or 2400 miles) is over open ocean, where the birds cannot feed. The ruby- throated hummingbird can fly nonstop across the Gulf of Mexico. Fatty acids pr

15、ovide the energy source for both these prodigious feats. In mammals, the major site ofaccumulation of triacylglycerols is the cytoplasm of adipose cells (fat cells). Droplets of triacylglycerol coalesce to form a large globule, which may occupy most of the cell volume (see Figure 22.1). Adipose cell

16、s are specialized for the synthesis and storage of triacylglycerols and for their mobilization into fuel molecules that are transported to other tissues by the blood. 脂肪酸脂肪酸 + + 甘油甘油 形成的酯形成的酯 根据结合的根据结合的脂肪酸分子数目脂肪酸分子数目又分为又分为： 单（脂）酰甘油；单（脂）酰甘油； 二（脂）酰甘油；二（脂）酰甘油； 三（脂）酰甘油：甘油三酯三（脂）酰甘油：甘油三酯/ /脂肪脂肪 二二 脂类的降解脂类

17、的降解 脂肪的水解：脂肪的水解： 甘油的代谢：甘油的代谢： 脂肪酸的分解代谢：脂肪酸的分解代谢： 激素敏感酯酶激素敏感酯酶 Triacylglycerols Are Hydrolyzed by Cyclic AMP-Regulated Lipases Triacylglycerols in adipose tissue are converted into free fatty acids and glycerol for release into the bloodstream in response to hormonal signals. A hormone- sensitive lip

18、ase initiates the process. The Utilization of Fatty Acids as Fuel Requires Three Stages of Processing Peripheral tissues gain access to the lipid energy reserves stored in adipose tissue through three stages of processing. First, the lipids must be mobilized. In this process, triacylglycerols are de

19、graded to fatty acids and glycerol, which are released from the adipose tissue and transported to the energy- requiring tissues. Second, at these tissues, the fatty acids must be activated and transported into mitochondria for degradation. Third, the fatty acids are broken down in a step- bystep fas

20、hion into acetyl CoA, which is then processed in the citric acid cycle. 激活的腺苷酸环化酶激活的腺苷酸环化酶 激活的蛋白激酶激活的蛋白激酶 激活的酯酶激活的酯酶 甘油生成甘油生成3-3-磷酸甘油磷酸甘油后进一步生成后进一步生成 磷酸二羟丙酮磷酸二羟丙酮进入糖酵解途径进入糖酵解途径 甘油还可以生成葡萄糖（糖异生）甘油还可以生成葡萄糖（糖异生） 甘油的代谢：甘油的代谢： 糖酵解糖酵解 甘油甘油 磷酸二羟丙酮磷酸二羟丙酮 葡萄糖葡萄糖 脂肪酸的脂肪酸的 - -氧化氧化 Acetyl CoA, NADH, and FADH2 Ar

21、e Generated in Each Round of Fatty Acid Oxidation Fatty Acids Are Linked to Coenzyme A Before They Are Oxidized 脂肪酸的活化脂肪酸的活化（线粒体外膜）线粒体外膜） 脂酰脂酰CoACoA转运入线粒体转运入线粒体 肉碱肉碱 脂酰脂酰CoACoA 脂酰肉碱脂酰肉碱 转运至转运至 线粒体基质中线粒体基质中 脂酰肉碱脂酰肉碱脂酰脂酰CoACoA 肉碱肉碱 肉碱肉碱 脂酰肉碱脂酰肉碱 脂肪酸脂肪酸 -氧化氧化反应反应 19041904年年 F.KnoopF.Knoop 的研究证明：的研究证明：

22、脂肪酸通过脂肪酸通过连续除去二碳单位连续除去二碳单位 而降解而降解 Fatty Acid Metabolism 脱氢脱氢 水化水化 脱氢脱氢 硫解硫解 脂肪酸脂肪酸 - -氧化的反应过程氧化的反应过程 脂肪酸脂肪酸 - -氧化氧化乙酰乙酰COACOA TCA TCA循环循环 NADH,FADHNADH,FADH2 2电子传递链氧化磷酸化电子传递链氧化磷酸化 活化时消耗两分子活化时消耗两分子ATPATP，净生成净生成 129129分子分子ATPATP 。 三三 1616碳的棕榈酸彻底氧化碳的棕榈酸彻底氧化 131131个个ATPATP Odd-Chain Fatty Acids Yield Pr

23、opionyl Coenzyme A in the Final Thiolysis Step Fatty acids having an odd number of carbon atoms are minor species. They are oxidized in the same way as fatty acids having an even number, except that propionyl CoA and acetyl CoA, rather than two molecules of acetyl CoA, are produced in the final roun

24、d of degradation. The activated three-carbon unit in propionyl CoA enters the citric acid cycle after it has been converted into succinyl CoA 四四 奇数碳原子脂肪酸的氧化奇数碳原子脂肪酸的氧化 丙酸丙酸丙酰丙酰C CO OA A 琥珀酰琥珀酰C COOA TCAA TCA循环循环 硫激酶硫激酶 丙酸丙酸丙酰丙酰COA COA ATPAMP 丙酰丙酰COACOA羧化酶羧化酶 丙酰丙酰- C COOA A D-甲基丙二酸单酰甲基丙二酸单酰C COOA A A

25、TPADP D-甲基丙二酸单酰甲基丙二酸单酰C COOA A琥珀酰琥珀酰C COOA A Odd-Chain Fatty Acids Yield Propionyl Coenzyme A in the Final Thiolysis Step Fatty acids having an odd number of carbon atoms are minor species. They are oxidized in the same way as fatty acids having an even number, except that propionyl CoA and acetyl C

26、oA, rather than two molecules of acetyl CoA, are produced in the final round of degradation. The activated three-carbon unit in propionyl CoA enters the citric acid cycle after it has been converted into succinyl CoA. 丙酰丙酰COA 琥珀酰琥珀酰COA 五五 酮体酮体( (Ketone Bodies) Ketone Bodies Are Formed from Acetyl Co

27、enzyme A When Fat Breakdown Predominates 丙酮丙酮 -羟丁酸羟丁酸 乙酰乙酸乙酰乙酸 前体；前体；乙酰乙酰CoACoA 肝中生成肝外组织分解肝中生成肝外组织分解 分解产物分解产物；乙酰乙酰CoACoA Formation of Ketone Bodies. The Ketone bodies-acetoacetate, d-3-hydroxybutyrate, and acetone from acetyl CoA are formed primarily in the liver. Enzymes catalyzing these reactions

28、are (1) 3-ketothiolase, (2) hydroxymethylglutaryl CoA synthase, (3) hydroxymethylglutaryl CoA cleavage enzyme, and (4) d-3-hydroxybutyrate dehydrogenase. Acetoacetate spontaneously decarboxylates to form acetone. Acetoacetate can be converted into two molecules of acetyl CoA, which then enter the ci

29、tric acid cycle. Ketone Bodies Are a Major Fuel in Some Tissues The major site of production of acetoacetate and 3-hydroxybutyrate is the liver. These substances diffuse from the liver mitochondria into the blood and are transported to peripheral tissues. These ketone bodies were initially regarded

30、as degradation products of little physiological value. However, the results of studies by George Cahill and others revealed that these derivatives of acetyl CoA are important molecules in energy metabolism. Acetoacetate and 3-hydroxybutyrate are normal fuels of respiration and are quantitatively imp

31、ortant as sources of energy. Indeed, heart muscle and the renal cortex use acetoacetate in preference to glucose. In contrast, glucose is the major fuel for the brain and red blood cells in well-nourished people on a balanced diet. However, the brain adapts to the utilization of acetoacetate during

32、starvation and diabetes (Sections 30.3.1 and 30.3.2). In prolonged starvation, 75% of the fuel needs of the brain are met by ketonebodies. Animals Cannot Convert Fatty Acids into Glucose It is important to note that animals are unable to effect the net synthesis of glucose from fatty acids. Specific

33、ally, acetyl CoA cannot be converted into pyruvate or oxaloacetate in animals. The two carbon atoms of the acetyl group of acetyl CoA enter the citric acid cycle, but two carbon atoms leave the cycle in the decarboxylations catalyzed by isocitrate dehydrogenase and a-ketoglutarate dehydrogenase. Con

34、sequently, oxaloacetate is regenerated, but it is not formed de novo when the acetyl unit of acetyl CoA is oxidized by the citric acid cycle. In contrast, plants have two additional enzymes enabling them to convert the carbon atoms of acetyl CoA into oxaloacetate . 六六 脂肪酸的生物合成脂肪酸的生物合成 （16C16C棕榈酸）棕榈酸

35、） 合成前体合成前体：乙酰乙酰CoACoA 反应部位反应部位：细胞质细胞质 1.乙乙酰酰COA的的转转运运 由线粒体转运至细胞质由线粒体转运至细胞质） 2.乙乙酰酰CoA的的羧羧化化 乙乙酰酰COA 丙二酸单酰丙二酸单酰COA 3.脂肪酸脂肪酸链链的合成（分的合成（分为为三三阶阶段行）段行）： 酰酰基的基的转转移：乙移：乙酰酰基基转转移到中央移到中央巯巯 基上再基上再转转移移 到外到外围巯围巯基上基上 脂肪酸脂肪酸链链的延伸：的延伸：缩缩合，合，还还原，脱水，原，脱水，还还原原 脂脂酰酰基的水解：硫解基的水解：硫解酶酶 乙酰乙酰COA的转运的转运 Transfer of Acetyl CoA

36、to the Cytosol. Acetyl CoA is transferred from mitochondria to the cytosol, andthe reducing potential NADH is concomitantly converted into that of NADPH by this series of reactions. 乙酰乙酰COA羧化酶羧化酶 丙二酸单酰丙二酸单酰COA The Formation of Malonyl Coenzyme A Is the Committed Step in Fatty Acid Synthesis Intermed

37、iates in Fatty Acid Synthesis Are Attached to an Acyl Carrier Protein The Elongation Cycle in Fatty Acid Synthesis Fatty Acid Synthesis. Fatty acids are synthesized by the repetition of the following reaction sequence: condensation, reduction, dehydration, and reduction. The intermediates shown here

38、 are produced in the first round of synthesis. II. Transducing and Storing Energy 22. Fatty Acid Metabolism 22.4. Fatty Acids Are Synthesized and Degraded by Different Pathways 酰基的转移：乙酰基转移到中央巯基酰基的转移：乙酰基转移到中央巯基 上再转移到外围巯基上上再转移到外围巯基上 乙酰乙酰COA+酰基载体蛋白酰基载体蛋白(ACP) 乙酰乙酰- ACP 丙二酸单酰丙二酸单酰COA + 酰基载体蛋白酰基载体蛋白(ACP)

39、 丙二酸单酰丙二酸单酰- ACP 脂肪酸合成酶复合体脂肪酸合成酶复合体 包括包括六种酶六种酶和一种和一种酰基载体蛋白酰基载体蛋白(ACP)(ACP)。各种生各种生 物脂肪酸合成过程相似，脂肪酸和酶系统均有物脂肪酸合成过程相似，脂肪酸和酶系统均有 上述上述六种酶六种酶和一种和一种酰基载体蛋白组成，酰基载体蛋白组成，但合酶但合酶 系统的组装形式不同。系统的组装形式不同。 大肠杆菌中，上述大肠杆菌中，上述6 6种酶以种酶以ACPACP为中心，有序地为中心，有序地 组成松散的多酶复合体。动物中，上述组成松散的多酶复合体。动物中，上述6 6种酶，种酶， ACPACP和和1 1种棕榈酰种棕榈酰-ACP-A

40、CP硫脂酶硫脂酶7 7种功能集于一条种功能集于一条 肽链酶系统为含肽链酶系统为含2 2个相同亚基的个相同亚基的2 2聚体。单聚体聚体。单聚体 无活性。无活性。棕榈酰棕榈酰-ACP-ACP硫脂酶硫脂酶只有在合成只有在合成1616碳的碳的 脂肪酸链后才有活性。其他生物缺乏此酶。脂肪酸链后才有活性。其他生物缺乏此酶。 酰基载体蛋白酰基载体蛋白(ACP)(ACP) 酰基转移酶（酰基转移酶（AT） - -丙二酸单酰转移酶（丙二酸单酰转移酶（MTMT） - -酮脂酰酮脂酰ACPACP合成酶合成酶（KSKS） - -酮脂酰酮脂酰ACPACP还原酶（还原酶（KRKR） - -羟脂酰羟脂酰ACPACP脱水酶（脱

41、水酶（HDHD） 烯脂酰烯脂酰ACPACP还原酶（还原酶（ERER） Fatty Acid Synthase Inhibitors May Be Useful Drugs Fatty acid synthase is overexpressed in some breast cancers. Researchers intrigued by this observation have tested inhibitors of fatty acid synthase on mice to see how the inhibitors affect tumor growth. A startlin

42、g observation was made: mice treated with inhibitors of the condensing enzyme showed remarkable weight loss due to inhibition of feeding. The results of additional studies revealed that this inhibition is due, at least in part, to the accumulation of malonyl CoA. Thus, fatty acid synthase inhibitors

43、 are exciting candidates both as antitumor and as antiobesity drugs. Acetyl Coenzyme A Carboxylase Plays a Key Role in Controlling Fatty Acid Metabolism Fatty acid metabolism is stringently controlled so that synthesis and degradation are highly responsive to physiological needs. Fatty acid synthesi

44、s is maximal when carbohydrate and energy are plentiful and when fatty acids are scarce. Acetyl CoA carboxylase plays an essential role in regulating fatty acid synthesis and degradation. Recall that this enzyme catalyzes the committed step in fatty acid synthesis: the production of malonyl CoA (the

45、 activated two-carbon donor). The carboxylase is controlled by three global signals glucagon, epinephrine, and insulin that correspond to the overall energy status of the organism. Insulin stimulates fatty acid synthesis by activating the carboxylase, whereas glucagon and epinephrine have the revers

46、e effect. The levels of citrate, palmitoyl CoA, and AMP within a cell also exert control. Citrate, a signal that building blocks and energy are abundant, activates the carboxylase. Palmitoyl CoA and AMP, in contrast, lead to the inhibition of the carboxylase. Thus, this important enzyme is subject t

47、o both global and local regulation. We will examine each of these levels of regulation in turn. SH SH ACPACP上有一个上有一个活性巯基活性巯基（中央巯基），（中央巯基）， - -酮脂酰酮脂酰-ACP-ACP合酶上也有一个合酶上也有一个活性巯基活性巯基（外围巯基）（外围巯基） 大肠杆菌脂肪酸合酶大肠杆菌脂肪酸合酶 ACP: SerACP: Ser残基上连残基上连 有有: : 4-4-磷酸泛酰巯基磷酸泛酰巯基 乙胺乙胺 缩合缩合 还原还原 脱水脱水 还原还原 脂肪酸链的延伸：缩合，还原，脱水，

48、还原脂肪酸链的延伸：缩合，还原，脱水，还原 脂酰基的水解脂酰基的水解：硫解酶硫解酶 -酮酮脂脂酰酰合成合成酶酶（KS）对对2C至至14C的的酰酰 基基ACP均有很高活性均有很高活性,而而对对16C的棕的棕榈酰榈酰 ACP活性很低活性很低。 棕榈酰棕榈酰-ACP硫脂酶只有在合成硫脂酶只有在合成16碳的脂肪碳的脂肪 酸链后才有活性。酸链后才有活性。 棕榈酰棕榈酰-ACP硫脂酶硫脂酶 七七 脂肪酸代谢调控脂肪酸代谢调控 快速调节快速调节； 柠檬酸柠檬酸激活激活乙酰乙酰C CA A羧化酶羧化酶 棕榈酰棕榈酰CoACoA抑制抑制乙酰乙酰C CA A羧化酶羧化酶 缓慢调节缓慢调节 基因调控基因调控动物饲喂

49、低脂肪饲料时动物饲喂低脂肪饲料时 乙酰乙酰C CA A羧化酶羧化酶 脂肪合成酶含量升高脂肪合成酶含量升高 八八 脂肪酸合成与分解的差别脂肪酸合成与分解的差别 区别点区别点 脂肪酸合成脂肪酸合成 脂肪酸脂肪酸-氧化氧化 反应部位反应部位: : 细胞质细胞质 线粒体线粒体 酶酶 7 7种多酶复合体种多酶复合体 4 4种酶种酶、 、是否多酶合体不明是否多酶合体不明 辅酶辅酶 NADPH FNDNADPH FNDHH NADNADHH 二氢单位二氢单位 丙二酸单酰辅酶丙二酸单酰辅酶A A 乙酰辅酶乙酰辅酶A A 载体载体 ACP ACP 辅酶辅酶 底物转运底物转运 柠檬酸穿梭作用柠檬酸穿梭作用 肉碱转

50、运肉碱转运 循环次数循环次数 7 7次次 7 7次次 反应方向反应方向 从甲基端向羧基端从甲基端向羧基端 由羧基端开始降解由羧基端开始降解 羟脂酰基的羟脂酰基的 立体结构立体结构 D D型型 L L型型 能量能量 消耗消耗7 7个个ATP 14ATP 14个个NADPH NADPH 产生产生 129129个个 ATPATP Fatty Acids Are Synthesized and Degraded by Different Pathways Conceptual Insights, Overview of Carbohydrate and Fatty Acid Metabolism, w

51、ill help you understand how fatty acid metabolism fits in withother energy storage and utilization pathways (glycolysis, citric acid cyclem,pentose phosphate pathwaym, glycogen metabolism), with a focus on carbonand energy flux. Fatty acid synthesis is not simply a reversal of the degradative pathwa

52、y. Rather, it consists of a new set of reactions, again exemplifying the principle that synthetic and degradative pathways are almost always distinct. Some important differences between the pathways are: 1. Synthesis takes place in the cytosol, in contrast with degradation, which takes place primari

53、ly in the mitochondrialmatrix. 2. Intermediates in fatty acid synthesis are covalently linked to the sulfhydryl groups of an acyl carrier protein (ACP), whereas intermediates in fatty acid breakdown are covalently attached to the sulfhydryl group of coenzyme A. 3. The enzymes of fatty acid synthesis

54、 in higher organisms are joined in a single polypeptide chain called fatty acid synthase. In contrast, the degradative enzymes do not seem to be associated. 4. The growing fatty acid chain is elongated by the sequential addition of two-carbon units derived from acetyl CoA. The activated donor of two

55、carbon units in the elongation step is malonyl ACP. The elongation reaction is driven by the release of CO2. 5. The reductant in fatty acid synthesis is NADPH, whereas the oxidants in fatty acid degradation are NAD + and FAD. 6. Elongation by the fatty acid synthase complex stops on formation of pal

56、mitate (C16). Further elongation and the insertion of double bonds are carried out by other enzyme systems. 脂肪酸分解脂肪酸分解 脂肪酸合成脂肪酸合成 九九 糖代谢为脂肪合成提供所有的原料糖代谢为脂肪合成提供所有的原料 甘油甘油 乙酰乙酰CoACoA NADPHNADPH（柠檬酸穿梭，磷酸戊糖途径）（柠檬酸穿梭，磷酸戊糖途径） ATPATP 十十 脂类的运输脂类的运输 游离脂肪酸游离脂肪酸（ （Free fatty acids、） 与清蛋白形成复合体运输与清蛋白形成复合体运输 中性脂肪，

57、胆固醇，胆固醇酯，磷脂中性脂肪，胆固醇，胆固醇酯，磷脂 与与蛋白质蛋白质结合成结合成脂蛋白脂蛋白(lipoprotein)形形 式运输。式运输。 四种脂蛋白四种脂蛋白 乳糜微粒（乳糜微粒（CMCM） 极低密度脂蛋白（极低密度脂蛋白（VLDLVLDL） 低密度脂蛋白（低密度脂蛋白（LDLLDL） 高密度脂蛋白（高密度脂蛋白（HDLHDL） Site of Cholesterol Synthesis. Electron micrograph of a part of a liver cell actively engaged in the synthesis and secretion of ve

58、ry low density lipoprotein (VLDL). The arrow points to a vesicle that is releasing its content of VLDL particles. Courtesy of Dr. George Palade. 极低密度脂蛋白（极低密度脂蛋白（VLDL） Schematic Model of Low-Density Lipoprotein. The LDL particle is approximately 22 nm (220 ) in diameter. 低密度脂蛋白（低密度脂蛋白（LDL） 胆固醇含量高胆固醇含

59、量高 中性脂肪含量高中性脂肪含量高 Endocytosis of LDL Bound to Its Receptor. (A) Electron micrograph showing LDL (conjugated to ferritin for visualization, dark spots) bound to a coated-pit region on the surface of a cultured human fibroblast cell. (B) Micrograph showing this region invaginating and fusing to form a

60、n endocytic vesicle From R. G. W. Anderson, M. S. Brown, and J. L. Goldstein. Cell 10 (1977): 351. III. Synthesizing the Molecules of Life 26. The Biosynthesis of Membrane Lipids and Steroids 26.3. The Complex Regulation of Cholesterol Biosynthesis Takes Place at Several Levels 低密度脂蛋白（低密度脂蛋白（LDL）受体）