生物化学本科课件英文版讲授chapter24fatty

1、CHAPTER 24 FATTY ACID METABOLISM FAs, containing a long hydrocarbon chain and a terminal carboxylate group, have 4 major physiologic roles e.g CH3(CH2)14COOHas building blocks of phospholipids磷脂磷脂 and glycolipids糖脂糖脂, these amphipathic (两亲两亲) molecules are important components of biological membrane

2、smany proteins are modified by the covalent attachment of FAs, which targets them to membrane locations膜定位膜定位FA are fuel molecules, stored as triacylglycerols (TAG三脂酰甘油酯三脂酰甘油酯) (neutral fats甘油与脂肪酸甘油与脂肪酸形成的不带电的酯形成的不带电的酯or triglycerides)FA derivatives serve as hormones and intracellular messengers 激素和

3、胞内信使激素和胞内信使(如前如前列腺素列腺素) TAG are highly concentrated energy stores TAGs are reduced and anhydrous (无水的无水的)The yield from the complete oxidation of FA is about 9 kcal/g, in contrast with about 4 kcal/g for carbohydrates and protein ( x 2)The reason for this is that FAs are much more highly reduced (C1

4、6H32O2 : C6H12O6)TAGs are very nonpolar and stored in a nearly anhydous无水的无水的 form ( x 3) (1克干糖原结合克干糖原结合2克克水水)a gram of nearly anhydous fat stores more than 6 times ( x 6) as much energy as a gram of hydrated glycogen this is why TAGs rather than glycogen were selected in evolution as major energy r

5、eservoirIn mammals, the major site of accumulation of TAG is the cytoplasm of adipose cells (fat cells) which are specialized for synthesis and storage of TAG their mobilization into fuel molecules that are transported to other tissues by blood TAG通常含有通常含有1424C之间的之间的偶数碳链脂肪酸，链可以是饱偶数碳链脂肪酸，链可以是饱和或不饱和的（

6、含一个或几个和或不饱和的（含一个或几个双键）。双键）。TAGs are hydrolized by cAMP-regulated lipases脂酶脂酶initial step in the utilization of fat as energy source: TAG+ 3H2Oglycerol+ 3 FAs +3H+ Hormones, such as epinephrine, norepinephrine (去甲肾上腺素去甲肾上腺素), glucagon and adrenocorticotropic hormone (促肾上腺皮质促肾上腺皮质) induce lipolysis：ho

7、rmonesadenylate cyclase腺苷酸环化酶腺苷酸环化酶cAMPprotein kinase A lipasecAMP is a second messenger in activation of lipolysis in fat cells, as it is in activation of glycogen breakdown In contrast, insulin inhibits lipolysis胰岛素抑制脂解胰岛素抑制脂解Glycerol is phosphorylated and oxidized to DHAP (and then isomerized to

8、GAl-3-P) which is on both glycolytic and GNG pathways 脂肪组织中储存的脂肪转变成其它组织所需的能量须脂肪组织中储存的脂肪转变成其它组织所需的能量须经历：经历：1. TAG降解为脂肪酸和甘油，从脂肪组织释放并运送到需降解为脂肪酸和甘油，从脂肪组织释放并运送到需能组织。能组织。 2. 脂肪酸被激活运送进入上述组织细胞的线粒体中进脂肪酸被激活运送进入上述组织细胞的线粒体中进行降解行降解 (氧化氧化) 。 3. 脂肪酸逐步降解为乙酰脂肪酸逐步降解为乙酰CoA，然后进入柠檬，然后进入柠檬酸循环。酸循环。FAs are degraded by the

9、sequential removal of two-carbon units Franz Knoop made a critical contribution to elucidation of mechanism of FA oxidationWhen a FA with an even (odd) number C was fed直链脂肪酸的直链脂肪酸的碳原子与苯环连碳原子与苯环连接接, phenylacetic acid苯乙酸苯乙酸 (benzoic acid苯甲酸苯甲酸) was produced FA are degraded by oxidation at the carbonTh

10、e use of a synthetic label (the phenyl group) and radioisotope label to elucidate reaction mechanisms is a landmark in biochemistry合成性标记物用于生物化学合成性标记物用于生物化学领域早于放射性同位素几十年领域早于放射性同位素几十年,它们用于它们用于阐明反应机制是生物化学发展史上的里阐明反应机制是生物化学发展史上的里程碑程碑 FAs are linked to coenzyme A before they are oxidized -oxidation of FAs

11、 occurs in mitoATP drives the formation of a thioester linkage between carboxyl group of FA and sulfhydryl group of CoA, making FAs activated脂肪酸羧基和脂肪酸羧基和CoA巯基之巯基之间间(由由ATP驱动驱动)形成硫酯键形成硫酯键(脂酰脂酰CoA),使脂肪酸活化使脂肪酸活化 This activation reaction occurs on outer mito membrane catalyzed by acyl CoA synthetase: R-

12、COO+ ATP+ HS-CoA (R-CO-AMP)脂酰腺苷酸中间物脂酰腺苷酸中间物 R-CO-S-CoA+ AMP+ PPi(以两个高能键为代价以两个高能键为代价)The hydrolysis of PPi drives the overall reaction irreversible a repeated theme: many biosynthetic reactions are made irreversible by hydrolysis of inorganic pyrophosphate焦磷酸水解焦磷酸水解Another recurring motif is: acyl ad

13、enylates脂酰腺苷酸中间物脂酰腺苷酸中间物(acyl-AMP) are frequently formed when carboxyl groups are activated in biochemical reactions被激活羧基经常与腺苷酸形成被激活羧基经常与腺苷酸形成酰基腺苷酸中间物酰基腺苷酸中间物e.g. in AA activation for Pro synthesis: AA+ATPAA-AMP(aminoacyl-AMP氨酰氨酰AMP)+PPi AA-AMP + tRNA AA-tRNA+AMP（氨基酸然后与（氨基酸然后与tRNA3端端AMP中核糖的中核糖的3羟基相连

14、羟基相连)。Carnitine 肉碱肉碱carries long-chain activated FAs into the mito matrix A special transport mechanism is needed to make long-chain acyl CoA molecules traverse inner mito membrane It is by conjugating (綴合綴合) long-chain FAs to carnitine, a zwitterionic (兼性兼性) compound formed from Lys来源于来源于Lys的兼性化合物的

15、兼性化合物acyl group is transferred from S atom of CoA to -OH of carnitine to form acyl-carnitineThis reaction is catalyzed by carnitine acyl transferase肉碱酰基转移酶肉碱酰基转移酶it is bound to outer mito membrane 线粒体外膜线粒体外膜(側側)Acyl carnitine is shuttled across inner mito membrane by a translocase 移位酶移位酶 acyl group

16、is transferred back to CoA on matrix side of membrane This reaction is catalyzed by carnitine acyl transferase肉碱酰基转肉碱酰基转移酶移酶Finally, carnitine is returned to cytosolic side by translocase, in exchange for an ing acyl carnitineIt is not required for permeation of medium-chain acyl CoAs into mito matr

17、ix C4C14(典型地典型地C8或或C10)脂酰脂酰CoA进入线粒体基进入线粒体基质不需肉碱质不需肉碱The defect in the transferase or translocase (or a deficiency of carnitine) will impair the oxidation of long-chain FAsdemonstrating that impaired flow of a metabolite from one compartment of a cell to another can cause disease Acetyl CoA, NADH, an

18、d FADH2 are generated in each round of FA oxidation saturated acyl CoA is degraded by a recurring sequence of 4 reactions oxidation by FAD: Acyl CoA+ E-FADtrans-2-enoyl CoA烯脂酰烯脂酰+E-FADH2Hydration水合水合: Trans-2 -enoyl CoA+ H2OL-3-hydroxyacyl羟脂酰羟脂酰CoAoxidation by NAD+: L-3-hydroxyacyl CoA+NAD+3-ketoacy

19、l酮脂酰酮脂酰CoA+ NADH+ H+thiolysis 硫解硫解by CoA: 3-ketoacyl CoA (n carbons)+ HS-CoAacetyl CoA+ acyl CoA (n-2 carbons) 脂酰脂酰CoA(n)“烯烯” “羟羟” “酮酮”脂酰脂酰CoA(n-2)+乙乙酰酰CoA112fatty acyl chain is shortened by 2 carbon atoms as a result of these reactions, and FADH2, NADH, and acetyl CoA are generatedThe former 3 reac

20、tions of 4 steps of -oxidation pathway in each round of FA degradation closely resemble the last steps in the citric acid cycle: (氧化与TCA循环中的对应几步)十分相似Acyl CoAenoyl CoAhydroxyacyl CoAketoacyl CoA Succ琥珀酸fum延胡索酸malate苹果酸OAA The preceeding reactions have oxidized -CH2- at C-3 to -C=O 碳原子碳原子(由亚甲基碳由亚甲基碳)被

21、氧化被氧化(为羰基碳为羰基碳)The long-chain, medium-chain, and short-chain acyl CoA DH catalyze FAs containing 12-18, 4-14, and 4和和6 carbons, respectivelyBy contrast, -ketothiolase -酮硫解酶酮硫解酶, hydroxyacyl CoA DH, and enoyl CoA hydratase have broad specificity 长、中、短链脂酰长、中、短链脂酰CoA脱氢酶氧化不同脱氢酶氧化不同(长度碳原子的长度碳原子的)底物底物, 而而

22、酶酶4（烯脂酰（烯脂酰CoA水合酶）、水合酶）、5（羟脂酰（羟脂酰CoA脱氢酶）、脱氢酶）、6（硫解酶）则普遍适用（硫解酶）则普遍适用(长、长、中、短链底物通用中、短链底物通用)The complete oxidation of palmitate棕榈酸棕榈酸 yields 106 ATP palmitoyl CoA+ 7FAD+ 7NAD+ 7H2O 8 acetyl CoA+ 7FADH2+7NADH+ 7H+ So, the yield of ATP is: 10 x8(acetyl CoA) +1.5x7(FADH2) + 2.5x7(NADH)2 =106 the complete

23、oxidation of a molecule of paltimate yields 106 ATP 脂代谢脂代谢Fatty acid: 8(acetyl CoA) +7(FADH2) +7(NADH) =8 x (3 NADH + FADH2 ) +7(FADH2) +7(NADH) =31 NADH+ 15 FADH2 In oxidative phosphorylation: 4H+ + 4e + O2 =2H2O (每一个还原型电子载体传递一对电子，每一个还原型电子载体传递一对电子，46个电子载体个电子载体(92个电子个电子)共需共需23个氧分子作为电子受体。每个软脂酸（即个氧分子作

24、为电子受体。每个软脂酸（即8个个acetyl CoA）完全氧化生成完全氧化生成16个个CO2， CO2 ：O2 =16：230.7糖代谢：糖代谢： Glucose: C6H12O6 +6O2 =6CO2+6H2O 糖酵解：糖酵解：2NADH；丙酮酸脱氢：；丙酮酸脱氢：2NADH （呼出（呼出2个个CO2 ）；）；TCA循环（呼出循环（呼出4个个CO2 ） ：6个个NADH 和和2个个FADH2 ；共产生；共产生12个还原型电子载体个还原型电子载体(24个电个电子子),即需即需6个氧分子作为电子受体个氧分子作为电子受体; 共呼出共呼出6个个CO2 CO2 ：O2 =1 以及其它（如蛋白等）有机物

25、质的氧化（量较小）以及其它（如蛋白等）有机物质的氧化（量较小）综上所述：综上所述： CO2 ：O2 0.8“In aerobic metabolism, about 0.8 equivalents of CO2 are produced per O2 consumed”(P164)需需(有有)氧代谢中氧代谢中,每吸入每吸入1分子氧气呼出分子氧气呼出0.8 分子分子CO2 。An isomerase and a reductase are required for the oxidation of unsaturated FA Take palmitoleate棕榈油酸棕榈油酸 (C16 Cis

26、-9) as an exampleit is C16 unsaturated FA with one double bond After activated and transported across the inner mito membrane in the same way as palmitatepalmitoleoyl CoA undergoes 3 cycles of degradation (-oxidation)However, the cis-3-enoyl CoA formed in the third round is not a substrate for the p

27、resence of cis-3 prevents formation of trans-2This impasse is resolved by a new reaction that shifts the position and configuration of the cis-3 double bondAn isomerase converts this double bond into a trans-2 double bond, which is a regular substrate in FA -oxidation 若干轮若干轮-氧化氧化后后,奇数双键都成为奇数双键都成为cis

28、-3;异构酶将异构酶将cis-3 转变成转变成trans-2 -氧化的正常底物氧化的正常底物(奇数双键的普遍解决方式奇数双键的普遍解决方式) (每一个奇数双键少每一个奇数双键少收获一个收获一个FADH2)Take linoleate亚油酸亚油酸 (C18 cis-9, cis -12) as another exampleThe cis-3 formed after 3 rounds of-oxidation is converted into trans-2 by the isomerase mentioned aboveIts cis-12 poses a new problem: a c

29、is-4 is formed after 4 rounds of-oxidationDehydrogenation of this species by acyl CoA DH yields a 2,4-dienoyl intermediate, which is not a substrate for the next enzyme in -oxidationThis impasse is circumvented by 2,4-dienoyl CoA reductase, an enzyme that uses NADPH to reduce cis-2, cis-4 to cis-3 将

30、两个顺式双键还原成一个将两个顺式双键还原成一个The isomerase then converts cis-3 to trans-2 若干轮若干轮-氧氧化后化后,偶数双键都成为偶数双键都成为cis-4;用用acyl CoA DH 生成生成trans-2, 这样形成了这样形成了2,4-二烯脂酰中间物二烯脂酰中间物;再用再用2,4-二烯脂酰二烯脂酰CoA还原还原酶酶(NADPH作为还原力作为还原力)将将trans-2, cis-4 还原为还原为cis-3,然后异构酶再将然后异构酶再将cis-3 转变成转变成trans-2 (此为偶数双键的普此为偶数双键的普遍解决方式遍解决方式) (每一个偶数双键

31、需消耗一个每一个偶数双键需消耗一个NADPH)Only two extra enzymes are needed for the oxidation of any polyunsaturated FAOdd-numbered double bonds are handled by isomerase一个奇数双键少收获一个奇数双键少收获一个一个FADH2，（相当，（相当于于1.5个个ATP）even-numbered ones by reductase and isomerase一个偶数双一个偶数双键需消耗一个键需消耗一个NADPH，（相当于，（相当于少收获少收获2.5个个ATP）Odd-cha

32、in FAs yield propionyl丙丙酰酰 CoA in the final thiolysis step The only difference between odd-chain FAs and even-chain FAs in-oxidation propionyl CoA and acetyl CoA are produced in the final round of degradationThe activated three-carbon unit in propionyl CoA enters TCA cycle after it is converted into

33、 succinyl CoA（P641）三碳的）三碳的propionyl CoA羧化生成四碳的羧化生成四碳的succinyl CoA进入柠檬进入柠檬酸循环酸循环 Ketone bodies酮体酮体 are formed from acetyl CoA when fat breakdown predominates “fats burn in the flame of carbohydrates”脂肪在糖的火焰中燃烧(脂肪在糖正常氧化的基础上氧化)acetyl CoA formed in FA-oxidation enters TCA only if fat and carbohydrate de

34、gradation are appropriately balancedbecause entry of acetyl CoA into TCA depends on the availability of OAAthe concentration of OAA is lowered if carbohydrate is unavailable or improperly utilizedOAA is normally formed from Pyr, the product of glycolysis 糖酵解的产物Pyr用来“添补”OAA(和TCA其它中间物)使得TCA循环持续进行In fa

35、sting or diabetes糖尿病糖尿病, OAA is consumed to form Glc by GNG and is unavailable for condensation with acetyl CoAUnder these conditions, acetyl CoA is diverted to formation of acetoacetate and D-3-hydroxybutyrate羟基丁酸羟基丁酸Acetoacetate乙酰乙酸乙酰乙酸, D-3-hydroxybutyrate and acetone丙酮丙酮 are called as ketone bod

36、ies 酮体酮体Acetoacetate is a major fuel in some tissues Acetoacetate and 3-hydroxybu-tyrate (its major site of production is liver) are normal fuels of respiration and quantitatively important as sources of energyheart muscle心肌心肌 and renal cortex肾皮质肾皮质 use acetoacetate in preference to Glc Glc is major

37、 fuel for brain and red blood cells脑和红细胞脑和红细胞 in well-nourished people on a balanced dietHowever, brain adapts to acetoace-tate during starvation and diabetesAcetoacetateacetoacetyl CoA (by CoA transferase)2 acetyl CoA (entering into TCA) liver can supply acetoacetate to other organs because it lack

38、s this particular CoA transferase (pay attention to glucokinase and G-6-Pase in liver!)肝脏是制造并输出酮体的主要场所。肝脏肝脏是制造并输出酮体的主要场所。肝脏缺乏缺乏CoA transferase，即不能利用酮体作为自身，即不能利用酮体作为自身燃料，这是肝脏利它性的又一体现。燃料，这是肝脏利它性的又一体现。Acetoacetate can be regarded as a water soluble, transportable form of acetyl units乙酰乙酸是乙乙酰乙酸是乙酰基的水溶性的

39、可转运形式酰基的水溶性的可转运形式High levels of acetoacetate in blood signify abundance of acetyl units and lead to decrease in rate of lipolysis in adipose tissue Animal cannot convert FAs into Glc animals are unable to convert FAs into Glcacetyl CoA cannot be converted into Pyr or OAA in animals动物不能把动物不能把acetyl C

40、oA转变成转变成OAA或其它或其它TCA循环的中间物循环的中间物(因通过每轮循环因通过每轮循环,它的两个碳原子以二氧它的两个碳原子以二氧化碳形式释出化碳形式释出,OAA不能视为不能视为acetyl CoA经经TCA氧化的氧化的产物产物),即不能将它转变为丙酮酸进而转变成糖即不能将它转变为丙酮酸进而转变成糖two C atoms of acetyl CoA enter TCA but two C atoms leave it OAA is regenerated but it is not formed de novo when the acetyl unit of acetyl CoA is

41、oxidized by TCAPlants are able to convert acetyl CoA into OAA (because of two additional enzymes(异柠檬酸裂合酶和苹果酸合异柠檬酸裂合酶和苹果酸合酶酶)植物通过乙醛酸循环能做到植物通过乙醛酸循环能做到(2个个acetyl CoA 转化成一转化成一个琥珀酸个琥珀酸)FAs are synthesized and degraded by different pathways Synthetic and degradative pathways are almost always distinctFA s

42、ynthesis is not simply a reversal of degradative pathwayIt consists of a new set of reactions and has some important features site场所场所: cytosolmito. immediate link中间物载体中间物载体: ACP酰基载体蛋白酰基载体蛋白CoA（both SH)enzyme integration形成酶复合体与否形成酶复合体与否: multienzyme complex(fatty acid synthase)seperated activated do

43、nor of two-carbon units活性二碳单位供体活性二碳单位供体: malonyl-ACP丙二酰丙二酰ACPacetyl CoA (released in degradation) reductant and oxidants还原剂和氧化剂还原剂和氧化剂: NADPHNAD+, FAD 方向方向synthesis: from methyl to carboxyl end合成从甲基合成从甲基到羧基端到羧基端 degradation: from carboxyl to methyl end降解从羧基降解从羧基到甲基端到甲基端elongation by FA synthase comp

44、lex stops upon formation of palmitate (C16) C16以上以上(脂肪酸脂肪酸)的合成和的合成和去饱和反应是由内质网上的酶系催化的去饱和反应是由内质网上的酶系催化的;氧化酶则可降氧化酶则可降解解16碳以上的脂肪酸碳以上的脂肪酸The formation of malonyl丙二酰 CoA is the committed step in FA synthesis acetyl CoA+ ATP +HCO3malonyl CoA+ ADP+ Pi+ H+ This irreversible reaction is committed step in FA s

45、ynthesisAcetyl CoA carboxylase contains a biotin prosthetic groupits carboxyl group is covalently attached to-amino group of a Lys residue just as in Pyr carboxylase羧化酶都以生物素为辅基羧化酶都以生物素为辅基, 都都在酶的在酶的Lys 残基的残基的-氨基与生物素的羧基之间形成酰胺氨基与生物素的羧基之间形成酰胺键键, 从而形成从而形成“长长的长长的,可伸缩的分子线可伸缩的分子线”The carboxylation steps of

46、acetyl CoA (to malonyl CoA) and Pyr (to OAA) are also similar: Biotin-E+ ATP+HCO3 CO2biotin-E+ ADP+ Pi CO2biotin-E+ acetyl CoA malonyl CoA+ biotin-E It exemplifies a ping-pong reaction mechanism乒乓反应乒乓反应机理：机理： one or more products are released before all substrates are bound This enzyme from E.Coli c

47、onsists of 3 subunitsbiotin carboxyl carrier protein生物素羧基载体蛋白生物素羧基载体蛋白biotin carboxylase生物素羧化酶生物素羧化酶Transcarboxylase转羧基酶转羧基酶length and flexibility of the link between biotin and its carrier protein enable activated carboxyl group to move from one active site to another in enzyme complex, as in Pyr c

48、arboxylaseIntermediates in FA synthesis are attached to an acyl carrier proteinACP Intermediates in FA synthesis in E.Coli are linked to sulfhydryl terminus巯基端巯基端 of phosphopantetheine磷酸磷酸泛酰巯基乙胺泛酰巯基乙胺 group of ACP In degradation of FA, this unit is a part of CoAin synthesis it is attached to a Ser r

49、esidue of ACP, a single polypeptide chain of 77 residuesACP can be regarded as a giant prosthetic group, a “macro CoA”CoA: 磷酸泛酰巯基乙胺磷酸泛酰巯基乙胺+AMP衍生物衍生物ACP: 磷酸泛酰巯基乙胺磷酸泛酰巯基乙胺+77个残基的肽链个残基的肽链(“巨巨CoA”)The elongation cycle in FA synthesis The enzyme system that catalyzes the synthesis of saturated long-chai

50、n FAs from acetyl CoA, malonyl CoA, and NADPH is called FA synthaseconstituent enzymes of bac. FA synthase are dissociated分散分散exist as multienzyme system in higher organisms多酶体系多酶体系 两者的两者的区别区别: 脂肪酸合酶的整体性脂肪酸合酶的整体性(高等生物以多酶复合体系形式存在高等生物以多酶复合体系形式存在,细菌中分离细菌中分离)FA synthetic reactions are similar in both or

51、ganisms相同点相同点:合成合成反应内容相似反应内容相似FAs with even (odd) number of C atoms are synthesized starting with malonyl-ACP丙二酰丙二酰 and acetyl-ACP乙酰乙酰3+2(propionyl-ACP丙酰丙酰3+3)malonyl-ACP is formed from malonyl CoA by malonyl transacylase MT转丙二酰酶转丙二酰酶acetyl -ACP (propionyl-ACP) is formed from acetyl CoA (propionyl-C

52、oA) by acetyl transacylase AT转乙酰酶转乙酰酶Just as the two “preparing” reactions in FA -oxidation, there are 3 “preparing” reactions in FA synthesis:三步三步“准备准备”反应反应(1个羧化两个转移个羧化两个转移),四步四步“正式正式”反应反应 acetyl CoAmalonyl CoA acetyl CoAacetyl-ACP malonyl CoAmalonyl-ACP The 4 “formal” reactions are: condensation,

53、reduction, dehydration and reduction. (oxidation, hydration, oxidation, thiolysis in FAoxidation)缩合缩合,还原还原,脱水脱水,再还原再还原(对比对比: 氧化氧化,水合水合,再氧化再氧化,硫介硫介)condensation (by acyl malonyl-ACP condensing enzyme CE)2+314, not direct 2+24why? Equilibrium for the synthesis of acetoacetyl-ACP乙酰乙酰乙酰乙酰ACP from 2 acet

54、yl-ACP is highly unfavorableIn contrast, equilibrium is favorable if malonyl-ACP is a reactant because its decarboxylation contributes a substantial decrease in free energy脱羧驱动反应向正向进行（而脱羧驱动反应向正向进行（而3碳底物在前一步骤被碳底物在前一步骤被羧化形成则以羧化形成则以ATP为代价）为代价）In effect, the condensation reaction is driven by ATP, thoug

55、h ATP does not directly participate in condensation reaction. ATP is used to carboxylate acetyl CoA to malonyl CoA. The energy thus stored in malonyl CoA is released in decarboxylation panying the formation of acetoacetyl-ACP 乙乙酰乙酰酰乙酰ACPAlthough HCO3 is required for FA synthesis, its C atom does not

56、 appear in the product（ HCO3 “先上去，再下来先上去，再下来”,它的碳它的碳原子没有渗入所合成的脂肪酸产物中原子没有渗入所合成的脂肪酸产物中)all carbon atoms of FAs containing an even number are derived from acetyl CoA (偶数偶数)脂肪酸中的全部脂肪酸中的全部C原子来自原子来自acetyl CoA The next 3 steps reduce the keto group酮基酮基 (C=O) at C-3 (-C atom) to a methylene group亚甲基亚甲基 (CH2

57、) acetoacetyl-ACP is reduced to D-3-hydroxybutyryl-ACP羟丁酰羟丁酰 (byketoacyl-ACP reductase KR 酮脂酰酮脂酰-ACP 还原酶还原酶)This reaction differs from the corresponding one in FA degradation in two respects: A. D rather L epimer is formed, and B. NADPH is the reducing agent (NAD+ in -oxidation)This difference exemp

58、lifies general principle that NADPH is consumed in biosynthetic reactions, whereas NADH is generated in energy-yielding reactionsD-3-hydroxybutyryl-ACP is dehydrated to form crotonyl-ACP (巴豆酰巴豆酰-ACP) which is a trans-2-enoyl-ACP 反式反式-2-烯脂酰烯脂酰ACP(catalyzed by 3-hydroxyacyl-ACP dehydratase 3-羟脂酰羟脂酰ACP

59、脱水酶脱水酶 DH) 乙酰乙酰乙酰乙酰(酮丁酰酮丁酰)羟丁酰羟丁酰烯丁酰烯丁酰(巴豆酰巴豆酰)丁丁(脂脂)酰酰crotonyl-ACP is reduced to butyryl-ACP丁酰丁酰 (by enoyl-ACP reductase ER 烯脂酰烯脂酰-ACP 还原酶还原酶), NADPH is again reductant (FAD is oxidant in corresponding reaction in -oxidation) In the second round of FA synthesis, butyryl-ACP condenses with malonyl-A

60、CP to form a C6-ketoacyl-ACP which is converted (through reduction, dehydration and reduction) into a C6-acyl-ACP “酮酮” “羟羟” “烯烯” 脂酰脂酰ACP (4 + 31= 6)Stoichiometry of FA synthesis 8 acetyl CoA+ 7ATP+ 14NADPH+ 6H+palmitate棕榈酸棕榈酸+ 14NADP+ 8CoA+ 6H2O+ 7ADP+ 7Pi (8 acetyl CoA ,7ATP and 14NADPH are consume