生物化學(xué)課件英文版教授講授下冊(cè)習(xí)題答案

1、EXERCISESCHAPTER171.(1) ATP 水解的G0 7.3(kcal/mol), creatineosate 水解的G010.3, 兩者偶聯(lián)的G0為 3,反應(yīng)向左。3.（a）總的G0 7.5(kcal/mol): 7.3 (14.8) = 7.5平衡時(shí)G=0； G=G0 +1.364 lg Keqlg Keq = G0/1.364 = 5.5;Keq = 3.06 x 106(b) Keq = PEP / ATPPyr,ATP / = 10,Pyr / PEP= 3.28 x 1044. 將 G-6-P（3.3）和 G-1-P（5.0）水解的G0疊加（偶聯(lián)）(= 1.7)然后計(jì)

2、算 Keq。（lg Keq = G0/1.364=1.25; Keq = 17.8G-1-P/ G-6-P） G-6-P G-1-P+ PPi）和 acetyl CoA 水解的G0（見 P451）各5. (a) ATP（為7.3 和7.5；總的G0為 0.2（b）Acee + ATP +CoA acetyl CoA + PPi (2 Pi)再與 PPi 的水解偶聯(lián) 0.28.0 = 7.8焦磷酸水解推動(dòng)反應(yīng)朝著形成 acetyl CoA 的方向進(jìn)行.這是生物化學(xué)中的一個(gè)普遍原則:生化反應(yīng)經(jīng)常與焦磷酸水解相偶聯(lián),從而推動(dòng)反應(yīng)朝著正反應(yīng)的方向進(jìn)行(使原本熱力學(xué)上不可行的反應(yīng)成為可行). 如 R-C

3、OO + CoA + ATP acyl CoA +PPi6. G=G0 +2.303RT lg Keq;G0 = 2.303RT lg Keq = 2.303RTG0 = 1.364; (1.364 x值小G0 值小4.8= 6.53)酸性強(qiáng)質(zhì)子轉(zhuǎn)移勢(shì)大Keq值大CHAPTER193. (a)G0=(4.0+ 0.43.4+ 5.7+ 1.8)+ 2x(1.54.5+ 1.1+ 0.47.5)+ 2x(6)= 29.5(b) Glc + 2Pi+ 2P4912 Lac +2ATP+ 2H2O P490, P497 G=G0+ 1.364 lgATP2Lac2/GlcPi22K=(2x10-3)

4、2(0.05x10-3)2/(5x10-3)(0.2x10-3)2(10-3)2=200G=29.5 + 1.364 lg200 = 27.2 kcal/molG=G0+ 1.364 lgKeq4. PEP+Pyr+ ATP平衡時(shí), G=0,可從表中查出G0值,即可計(jì)算出KeqPEP /Pyr=3.06 x 105Keq = PyrATP/PEP“很高的轉(zhuǎn)移勢(shì)”指 PEP(即使在PEP /Pyr很小時(shí))能將磷生成 ATP酸基轉(zhuǎn)移給5. F-1,6-BPGAl-3-P +DHAPaldolase(醇)醛縮(合)酶G=G0+ 1.364 lgKeqG0 Keq x0.001xxxKeq= x2/0

5、.001x8（a）1，3-BPG2,3BPGoxygen affinity of Hb高(低)水平糖酵解產(chǎn)物導(dǎo)致血紅蛋白氧氣親和力的降低(增強(qiáng))（b）己糖激酶缺陷,即糖酵解受阻糖酵解中間物缺乏即 2,3BPG血紅蛋白氧氣親和力（c）酸激酶缺陷,糖酵解出口受阻糖酵解中間物血紅蛋白氧氣親和力9. F-1-P 途徑(直接)形成 Gal-3-P 繞過 PFK(使得過多的酵解產(chǎn)物不能有效抑制PFK), F-1-P(見P491)還刺激生成過多乳酸;.過多乳酸生成導(dǎo)致酸12.（a）PFK 的 ATP 變構(gòu)位點(diǎn)丟失能量充足信號(hào)不能抑制糖酵解糖酵解步伐PFK 的檸檬酸結(jié)合位點(diǎn)丟失糖酵解產(chǎn)物(乙酰輔酶 A) 充足

6、信號(hào)不能抑制糖酵解糖酵解步伐調(diào)控 F-2,6-BP 水平的雙功能酶中磷酸酶結(jié)構(gòu)域丟失 磷酸化功能F-2,6-BP 形成糖酵解步伐（d酸激酶()中 F-1,6-BP 結(jié)合位點(diǎn)失糖酵解前體步驟標(biāo)志物充足信號(hào)不能刺激CP CC糖酵解步伐C C C C C C P(G-6-P)C C C P(F-1,6-BP)C P C C(DHAP)C CC PCC C P(GAl-3-P)+(GAl-3-P)C P C C P(1,3-BPG)C CC P(3-PGA)CC PCC C P C(PEP)COOH C=O CH3(Pyr)(2-PGA)（糖酵解：葡萄糖標(biāo)記的一號(hào)碳原子出現(xiàn)在酸的甲基碳中）COOCOO

7、COOCOOCH3+C=O C=OCH2CH2CH2HOCCOOCH2 COOHCCOOHCOH COOCH2COO-CH2+CO2C=O COO(OAA)(acetyl CoA)(citrate)(isocitrate)(-KG)COOCH2CH2 COO+CO2(succinyl CoA)(上述酸標(biāo)記的甲基碳經(jīng)過氧化脫羧出現(xiàn)在乙酰輔酶 A乙?；募谆贾?，經(jīng) TCA 循環(huán)的前四步，此標(biāo)記的碳原子出現(xiàn)在二羧酸的 2,3 碳原子中)CHAPTER201.(a)Pyr 中的甲基碳(b)Pyr 中的羧基碳Pyr 中的羰基碳(d)acetyl CoA 甲基碳(e)G-6-P 中的1 號(hào)碳a,d,e

8、甲基碳經(jīng)過一輪檸檬酸循環(huán)出現(xiàn)在 OAA 的 C-2(C-3)中.2.(a)Isocitratelyase(6=4+2)andmalatesynenzymes of citric acid cyclese(2+2=4)+(b)one round of glyoxylate: 2acetyl CoA + NAD+ + 2H2O succinate + 2CoA + NADH + 2H+from succinate to OAA in one round of citric acid cycle:succinate + H2O + FAD + NAD+ OAA + FADH2 + NADH+H+)

9、2acetyl CoA + 2NAD+ + FAD + 3H2OOAA + 2CoA +2NADH + FADH2 + 3H+(ADH)4. CH3-CH2-OH + NAD+ CH3CHO +NADH + H+(Gal-3-P DH)1,3-BPG + NADH + H+ Gal-3-P(no H) + NAD+ + Pi(NAD+內(nèi)含一個(gè) H)deuterated:氘標(biāo)記的結(jié)論:脫氫酶與輔酶(NAD+或 NADH)的結(jié)合有兩種不同的方式:ADH 醇脫氫酶(和lac DH 乳酸脫氫酶)與輔酶(NAD+)結(jié)合的特異性是A 型的(即A 位朝外)而Gal-3-P DH 三磷酸甘油醛脫氫酶(和 ma

10、late DH 蘋果酸脫氫酶)與輔酶(NAD+)結(jié)合特異性是 B 型的(即 B 位朝外,環(huán)平面旋轉(zhuǎn)了 180 度)的(見圖 20-16,酰胺環(huán)中, 酰胺基書寫在右側(cè),則 C4 連接氫原子有兩個(gè)不同的位點(diǎn):朝平面外(內(nèi))的為A(B)位; C4 連接一(二)個(gè)氫原子時(shí)為 NAD+(NADH). 5.thiazolone 噻唑酮6.malate + NAD+OAA + NADH 令MALATE/OAA =xG =G0 + 1.364 lgOAANADH/MALATE NAD+7= 1.364 lg 1/8xx=1.75 x 104the value x must be greatern 1.75 x

11、 104for OAA to be formed結(jié)論:在穩(wěn)態(tài)條件下OAA是以催化量(即極低濃度)存在的.9. Dj vu 似曾相識(shí);和水解 F-2,6-BP 的雙功能酶與(其激酶和磷酸酶的活性部位在不同的區(qū)域)相反,修飾異檸檬酸脫氫酶的雙功能酶(P524)用同一個(gè)活性中心催化相反的反應(yīng).CHAPTER211. (b)LacPyr (+1 NADH)(12.5+2.5=15 or 12.5+1.5=14)(c) GlcG-6-P(1)F-6-PF-1,6-BP(1)(30+1+1=32)(d)PEPPyr (+1)(12.5+1=13.5)(e)Gal 半乳糖+ATPGal-1-P(1) +UD

12、P-GlcG-1-P廠G-6-P(311=30)(f)DHAP 磷酸二羥基 GAl-3-P 三磷酸甘油醛1,3-BPG(+1 NADH)3-PGA(+1)2-PG(12.5+2.5+1+1=17 or 12.5+1.5+1+1=16)PPyr(+1)能的改變G0(化2.標(biāo)準(zhǔn)氧還電位(差) E0標(biāo)準(zhǔn)學(xué)反應(yīng)的)平衡常數(shù)Keq(規(guī)定)氫離子濃度(的差異)E0=G0/nF=(RT ln Keq)/nF =2.3 RT lg Keq /nF = 2.3 x 1.987 x 103 x 298 lg Keq/23.063n=(1.364/23.063n ) lgKeq = (0.059/n )lg Keq

13、E0=(0.059/n) lg Keq或由 Nernst 方程：E01= E0+ (0.059/n) lgox1/red (生物化學(xué))E02= E0+ (0.059/n) lgox2/red (普通化學(xué))2H+ +2eH2(Keq=ox/red), n=2E0= E01E02=0.059/n lg (107)2lg (100)2=0.059=0.42V(H+=107 M;H+=1M)結(jié)論：每增加 1 個(gè), E 值減少 0.059V化學(xué)教科書上( =0)2H+/H2: 0V;O2/H2O:1.23V生化教科書上( =7)2H+/H2:0.42V; O2/H2O:0.82VPi/O 磷氧比(ind

14、ex of OP)2e + 2H+ + 1/2O2 = H2O4P:O每消耗一個(gè)氧原子(即傳遞一對(duì)電子)摻入到有機(jī) ATP中的無機(jī)磷酸數(shù)(即消耗的無機(jī)磷酸數(shù)) （NADH：2.5;FADH2: 1.5）(a) H+(translocated)/2e 每傳遞一對(duì)電子被泵出的質(zhì)子數(shù)質(zhì)電比 (NADH:10;FADH2: 6)P/ H+每一個(gè) ATP 并將它轉(zhuǎn)移到胞質(zhì)所需質(zhì)子數(shù)(的倒數(shù))磷質(zhì)比(1/4)5. thermodynamic constra熱力學(xué)限制E0 for Fum./succi.= 0.03V;E0 for NAD+/NADH=0.32Vsucci+ NAD+Fum. + NADHE

15、0 for FAD/FADH2=0VE=0.32V0.03V=0.35V(以 NAD+作為氧化劑)E=0V0.03V=0.03V(以 FAD 作為氧化劑) G0=nFE =46x(0.35)= 16.1 kcal/mol (以 NAD+作為氧化劑)G0=nFE=46(0.03)=1.4 kcal/mol(以 FAD 作為氧化劑)結(jié)論:琥珀酸被 NAD+氧化(成延胡索酸)在熱力學(xué)上不可行;而被 FAD 氧化(成延胡索酸)在熱力學(xué)上可行.6.cyanide antidote化物解毒劑nitrite 亞硝酸鹽化物與細(xì)胞色素氧化酶中 Fe3+相結(jié)合(阻斷氧化磷酸化)而致死; 亞硝酸鹽可將血紅蛋白中的

16、Fe2+氧化成 Fe3+,后者與化物結(jié)合.即鐵血紅蛋白可與細(xì)胞色素氧化酶爭(zhēng)奪化物.且前者的(不損害載氧功能的可用)量遠(yuǎn)大于后者(故可用于治療).8. G =nFE=G0 +2.3 RT lg KeqE=0.2V,so G =n x 23 x 0.2=4.6 n kcal/mol+ Pi = ATP + H2OKeq= ATP H2O / PiA. n=2 G =4.6x2=9.2 kcal/mol9.2=7.3 +1.364lg KeqKeq=101.9/1.364=26.213.8=7.3 +1.364lg KeqKeq=106.5/1.364=6.51x104B. n=3(線粒體懸浮液AT

17、P 一直達(dá)到這一比值的程度)C. n=4結(jié)論:Keq=1011.2/1.364=1.62x108一個(gè)(摩爾)ATP 消耗的能粒體懸浮液中每量約 13 千卡,即需移位約 3 個(gè)質(zhì)子(而不是 7.3 千卡,即不是移位約 2 個(gè)質(zhì)子)10. dicyclohexylcarbodiimideDCCI 二環(huán)己基亞胺CHAPTER221. C6*P-C-C-C-C-C1(G-6-P)C5*P-C-C-C-C1 (Rib-5-P) +CO22. 6-osogluconate ( -ketoacid葡萄糖酮酸)Rib-5-P +CO2isocitrate (oxalosuccinate 草酰琥珀酸) -KG

18、+CO2脫氫 + 脫羧3. Rib-5-P:C5P-C-C-C-C1* (Xyl-5-P) + C5P-C-C-C-C1* (R-5-P)C3P-C-C1 (GAl-3-P) + C7P-C-C-C-C*-C-C1*(Sed-7-P)C4P-C-C-C1 (Ery-4-P) + Cp(6)-C-C-C*-C-C* (1) (F-6-P)6. TA+ substrate Schiff base + NaBH*4 Lys*(in TA )labeledfingrtritiated 氚標(biāo)記的H +H+2GSH+N+7.GSSG+NGSSG+2e2GSH(1)H +H+E0=0.23V+N+2eN(2

19、)E0=0.32V(1) (2) E0=0.09VG0=nFE0 = 46x 0.094.15 kcal/mol=G=G0+ 1.364 lg KeqKeq=104.15/1.364=1126Keq=GSH2N+/GSSG NH/ NH= GSH2/GSSGx+)1/X(X=NX=1/ Keq x GSH2/GSSG=1/1126 x (10)2/1=8.9 x 102 (?) X=1/ Keq x GSH2/GSSG=1/1126 x (102)2/103=8.9 x 1058. (because of F-1,6-BPase deficiency 此酶對(duì) F-2,6-BP 調(diào)控不敏感) G

20、lc（GNG）produce heat (substrate cycling),F-1,6-BPPyracetyl CoAATP9.biotin + Lys-Pyr carboxylase carrier of activated CO2 (fromHCO3 +ATP to Pyr)lipoic acid +Lys-dihydrolipoyl acetyltransferas（e E2）carrierof acetyl group (from TPP to CoA)10. Avidin 親和素, 抗生物素蛋白Chapter 23 習(xí)題1.G-1-P+UTP+glycogenn+H2Oglyco

21、genn+1+UDP+2Pi (P588:(2)(4) )+H+Gal+ATP G-1-P+(P492)Total:Gal+UTP+ATP+glycogenn+H2O glycogenn+1+UDP+ 2Pi+H+2. glycogen*+(Pi+E) G-1-P/Glc=100 (該glycogen+(Pi+E) G-1-P/Glc=10 (正常人)cause: branching enzyme deficiencymuch little branching的分枝酶缺陷,導(dǎo)致該由于糖原糖原時(shí)分枝比正常人少十倍3.(P598)G-6-Pase(ortransporter) G-6-P (oso

22、rylated glycogen synse ba) glycogen5.(P585,503)G-1,6-BP(fromG-1-P+ATP)makestheutase (notosorylated)osorylated.8.(a)P590無活性 Eb-有活性 Ebdegradation變構(gòu)效應(yīng)物不起作用，只有可逆磷酸化才能使磷酸化酶成為 Ea型(b)P590Eb-Eadegradation肝糖原動(dòng)用受阻(c)kinase 過度表達(dá)osorylation of Eactivation ofEdegradationlittle glycogen present(d)P596loss of the

23、geneinhibitor of PP1PP1osorylase aor bdegradation(e) loss of te of G subunit of PP1PP1去磷酸化能力大大下降 (P596)syndegradationse andosorylase(f)glycogeninblock the initiation of glycogen synthesisChapter24習(xí)題+NADH+H+ (P606)ate DH)1. (A)glycerol+ATP+NAD+DHAP+(glycerol kinase and glycerol(B)DHAP(GAl-3-P)+NAD+2o

24、s+PiPyr+NADH+H+2ATP+ H2OTotal: glycerol+ 2NAD+2H+ + H2O2. (A) stearate 硬脂酸+ATP+CoAPPi+ H2O2Pi+PiPyr+ ATP+ 2NADHstearyl-CoA+(P607)+PPi(B) stearyl-CoA+8FAD+8 NAD+8CoA+8 H2O9acetylCoA+8FADH2+8NADH+8H+(P611)(C) 2acetylCoA+ H2Oacetoacee+2CoA (4.5)(P612)stearate+ATP+13.5H2O+8FAD+8NAD+total:e+14.5H+8FADH2+

25、8NADH+4.5acetoace+2Pi4.palmitoleate 棕櫚油酸（16:1 cis9） -7oleate 油酸（18:1 cis9）-9(7 可以自身)linoleate 亞油酸（18:2 cis912）-6linolenate 亞麻酸（18:3 cis91215）-3 (哺乳動(dòng)物沒有這樣的酶:可以將雙鍵引入脂肪酸的第九以上的碳原子.7 只能從必需脂肪酸獲得,并以此為基礎(chǔ)再延長(zhǎng)和去飽和)5. CH3(CH2)nCOOHCH3(CH2)n+1 CH2COOHCH3(CH2)n+1CH2CH2 CH2COOH方向由甲基到羧基,即最后加入的二碳輔酶 A 提供)出現(xiàn)在羧基端.丙二酰輔酶

26、A 三個(gè)碳原子都 14C 標(biāo)記加入到的細(xì)胞提取液中一分鐘后改變此提取液的(由丙二酰脂肪酸使反應(yīng)突然中斷(假定含放射性C 多?一個(gè)棕櫚酸約需),C-1 還是 C-146. see “aldolase form a Schiase with DHAP” (P500); enolate烯醇化. 一個(gè)硫酯的烯醇化陰離子()進(jìn)攻另一硫酯的羰基碳原子(+)形成CC 鍵7. (Pyr)OAP (+CO2) in gluconeogenesis 糖異生8. surfeit 過量 promotor muionprotein kinaseA (adie cell)lipase(byosorylation) (P6

27、06 line4)breakdown of TAGand depletion ot stores 級(jí)聯(lián)放大系統(tǒng)通過使脂(肪)酶磷酸化(促活它),從而促進(jìn)脂肪降解9. Ser in acetyl CoA carboxylase (theof protein kinase) ismuedo Alaactivity of acetyl CoA carboxylase(notinhibited byosorylation 原本是受磷酸化抑制的) FAsynthesisobesity 肥胖10. blocked assets 被阻斷的Carnitine 肉堿 translocase 移位酶 defici

28、encyimpairedtransport of acyl from cytosolo Mito (FA)G-6-P transporter deficiencyimpaired transport of G-6-Pfrom cytosolo endoplasmic reticulum (and then Glc fromERo blood)(Glc)Chapter25Exercises1. (d) Leu -ketoisocaprate-酮苯(P645)(P649)(P647)酸(e)e enylpyruvate酸(f) Tyr AlaPyr;ydroxyenylpyruvate 對(duì)羥苯As

29、pOAA;Glu-KG2(a)AspGlc (by OAA)AAsp+-KG OAA+Glu(aminotransferase-PLP)B. OAA+GTP PEP+CO2+GDP (PEP carboxykinase-Biotin) (P573)C.PEP+ATP+NADH+H+2H2O Glc+NAD+2Pi+(enzymes flycolysis and F-1,6-BPase, G-6-Pase)(P571, P574)Asp+ -KG+GTP+ATP+2H2O+NADH+H+Total:+ GDP+NAD+2Pi1/2 Glc+ Glu+CO2+AspOAA (by Fum.)(b)

30、+A. CO2+NH4 +3ATP+Asp+2H2O Urea+ 2+2Pi+PPi+Fum(P636)B. Fum+H2O+ NAD+ OAA+NADH+ H+Asp+ CO2+NH4 +3ATP+4H2O+ NADTotal:+ NADH+ H+OAA+ Urea+2+4Pi+4. Pyr DH TPP轉(zhuǎn)氨酶中 PLP（中的氮原子）以及Pyr DH 酶中 TPP 焦磷酸硫胺素（噻唑環(huán)中的氮原子）作為電子穴穩(wěn)定負(fù)碳離子（中間物）(515)5. guanidinium 胍基（P635）N+ as electron sink6.底物中的標(biāo)記氘轉(zhuǎn)移到輔酶（與基交換）這個(gè)氘留在輔酶中，輔酶中另一氫原

31、子將產(chǎn)物中基換回基:具未配對(duì)電子,共價(jià)鍵均裂形成8. A. CO2+NH4+3ATP+Asp+2H2O Urea+ 2+2Pi+PPi+FumB. Fum+ H2O+ NAD+ OAA+ NADH+ H+C. OAA+Glu Asp+-KG+Total: CO2+NH4 +3ATP+ NAD + 3H2O+GluUrea+29. 2,4-二+2Pi+ PPi+NADH+ H+-KG (4P)肼（尿檢） +質(zhì)譜測(cè)定：deficiency of allthree enzymes complex(Pyr DH complex; -KG DHcomplex; branched-chain-keto D

32、H complex) (P645)the deficiency of the common enzyme “E3”(三個(gè)脫氫酶系共同含有的二氫硫辛酰胺脫氫酶: DihydrolipoylDH 缺陷)10.Cit瓜氨酸 +Asp argininosuccinate(byargininosuccinate synthetase 精氨酰琥珀酸酶)e 苯乙酸,Treatment: benzoate 苯甲酸,Arg, protein-restricted dietenylacetreatment: providing protein-restricted diet with large amounts

33、ofbenzoate (苯甲酸) andenylacee (苯乙酸) hippurate (馬尿酸) (benzoyl CoA+ Gly) andenylacetyl glutamine (苯乙酰谷氨酰胺) (enylacetyl CoA+ Gln)排出：馬尿酸，苯乙酰谷氨酰胺和瓜氨酸 (與治療氨甲酰磷酸酶以及鳥氨酸轉(zhuǎn)氨甲酰酶缺陷類似, P637)11. aspartame:苯丙二肽酯 （L-氨酰-L-苯丙氨酸甲酯；增甜劑）Chapter1. (A) Glycerol+ATPGlycerol-3-P+27通DHAP 還原生成(P606)(B) Glycerol-3-P + acetyl CoA

34、 lysoosatidate + CoAlysoosatidate + acetyl CoAosatidate 磷脂酸+ CoAosatidate +H2O DAG+ PiDAG+ acetyl CoA TAG+ CoA(P686)(C)FA+ CoA +ATP acetyl CoA+PPix3(P607)total:Glycerol+4ATP+4H2O+3FA TAG+3+7Pi+4H+(P1027)2.(A)Glycerol+ATPGlycerol-3-P+(P606)(B) Glycerol-3-P + acetyl CoA lysoosatidate + CoAlysoosatidat

35、e+acetylCoA osatidate磷 脂 酸 +CoA(P686)(C) FA+CoA+ATPacetylCoA+PPix2(P607)(D)osatidate+CTPCDP-DAG+PPi(P686)(E)CDP-DAG+Shosotidyl Ser+ CMPtotal Glycerol+ 3ATP+ 2H2O+ 2FA+ CTP+Shosatidylserine+CMP+2+6Pi+3H+(P1027)3.(a)CDP-DAG: activatedosatidyl group 活性磷脂酰( 從頭合成)P687(b)CDP-enolamine（+DAG）: activatedosor

36、ylenolamine活性磷酸乙醇胺(節(jié)約利用途經(jīng))P688(c)acyl CoA: activated acyl group 鞘氨醇神經(jīng)酰胺; 活性脂?；?d)CDP-choline: activatedosoryl choline 神經(jīng)酰胺鞘磷脂; 活性磷酸膽堿(P690 Fig 27-6 wrong pringwrong:osatidylcholine DAG; correct: CDP-cholineCMP)書中似有誤(e)UDP-Glc(or -galactose): activated Glc group 神經(jīng)酰胺腦苷脂;活性葡糖(或半乳糖)(f)UDP-Gal: activate

37、d Gal group (P690, 691) 神經(jīng)節(jié)苷脂 GM2神經(jīng)節(jié)苷脂 GM1; 活性半乳糖(g)GPPFPP; GPP 活性十碳(它的焦磷酸“尾”脫去)4.(a)MVAIPP(P693) 6C5C 羧基碳在脫羧時(shí)脫去(b)malonyl CoAacetoacetyl CoA (P693 and P617); 3+214C 脫羧時(shí)脫去both carboxyl C 羧基碳 losthe reactions5. No receptor receptors cant reach the plasma membrane （缺乏胞內(nèi)轉(zhuǎn)運(yùn)信號(hào)或不正確折疊）fail to bind LDL norm

38、ally（LDL 結(jié)合功能域缺陷） fail to cluster in coated pits(不能在被膜小坑成簇；因羧基端區(qū)域缺陷).6.兩個(gè)可能：DNA:（GA？）（CT）可能性不如 RNA 中（CU，僅脫氨）可能性大RNA ： C U (deamination 脫氨), so CAA(Gln) UAA(stop) and apo B-100 肝apo B-48 腸；（DNA）突變可能性不大（因肝中蛋白正常），是腸（轉(zhuǎn)錄時(shí)）RNA 改變（脫氨）所致7雄激素（androgen）的某些功能被二氫睪酮（dihydrotestosterone）介導(dǎo)，后者由睪酮（testosterone）還成，這

39、一步由依賴 NH的 5-還原酶催化。此還原酶缺陷的、為 XY 的出生時(shí)具內(nèi)尿殖道（ernal urogenital tract），但（externalgenitalia）主要是女性的。他們通常被視為。到puberty），由于睪酮水平的升高而呈現(xiàn)陽性化（masculinize）。這些還原酶缺（testes）正常，而（prose gland）較小。陷的男子此信息如何用來設(shè)計(jì)一種治療良性過度生長(zhǎng)（ benignprosic hypertroy）正常老化（aging）過程中的常見病的藥物？大多數(shù) 55 歲以上男子都患有某種程度的腫大（enlargement），這常導(dǎo)致阻塞（urinary obstru

40、ction）。Answer:testosterone睪酮dihydrotestosterone 二氫睪酮 (by 5-redue)theenlargement(腫大) can be treated by inhibitingthe 5-redue( 還原酶 ).Finasteride,the4-azasteroidogofdihydrotestosterone(二氫睪酮的-4 氮類似物), competitivelyinhibitsthe redue but does not act on androgen receptors 雄激素受體.Finasteride 藥物還原酶 睪酮dihydro

41、testosterone(二氫睪酮)but testosterone 睪酮 normal prose()essmaller but testosterone-dependent proses (fertility 生殖, libido 性欲 and muscle strength) unaffected.8.drugidiosyncracies: 藥物特異性;peoplemostsensitivetodebrisoquine（to treat hyperten）deficiency of a liver P450enzyme(ahydroxylasecatalyzing:debrisoquin

42、e hydroxydebrisoquine) gene deficiency: a member of CYP2 subfamilypayattention to exercising in giving other drugs to the above-mentionedpeople(the enzyme handles a broad range of substrates).9.deficiencyof21-hydroxylase,also11 -hydroxylase,17 -hydroxylase, 3-DH, and desmolase 碳鏈酶 adrenal hyplasia腎上

43、腺畸型生長(zhǎng)virilization化 and enlargement of the adrenals腎上腺腫大。10.hydroobic odorants 疏水性有氣味物質(zhì) are deactivated byhydroxylation.O2isactivatedbyacytochromeP450monooxygenase. NH as reductant.Chapter28(glycolysis)1. (1)GlcPyr(2)PyrAla(Glu; aminotransfer)total:+2.N2 NH4 (A)Glu (B)Ser (C)Gly (D) -aminolevulinate-

44、氨基酮戊酸(E)porobilinogen 膽色素原（F）Heme（G）+(A)N fixation, (B)NH4 assimilation, (C)aminotransf719), (D)FH4methylene, (E)與 succinyl CoA 縮合（限速步驟）(F) 二分子-氨基酮戊酸縮合 (G)血紅素3(a) Gly+N5,N10-methelene-FH4 +H2OSer+ FH4 亞甲基(P719)(b)HomoCys 高半胱 + N5-methyl FH4 Met+FH4 甲基(P722)4（P717）5.isovaleric acidemia 異戊酸血癥Leuisoval

45、eryl異戊酰CoA methylcrotonyl甲 基 巴 豆 酰 CoA(P645)（isovaleryl CoA DH）treatment: isovaleryl CoA + Gly isovalerylglycine 異戊酰甘氨酸（水溶性的, in contrast with isovaleryl acid）excreted bykidneys7.cysteine 半胱氨酸 and cystine 胱氨酸cytosol is more reductive -SH group within cells is not easilyoxidized由于胞內(nèi)環(huán)境還原性較強(qiáng), 胞內(nèi)蛋白缺乏二硫鍵

46、,而胞外蛋白卻含有(較多)二硫鍵8To and fro 往復(fù)，血紅素的限速步驟（Gly+succinyl CoA）發(fā)生粒體（其它步驟均在細(xì)胞質(zhì)中進(jìn)行），原因是 succinylCoA 是檸檬酸循環(huán)中粒體內(nèi)形成的9.dangerous trap的截獲Pernicious anemia 惡性貧血(內(nèi)因子缺乏所致 P644)VB12 deficiencythe methyl transfer reactionblocked (HomoCys + N5- methyl FH4 -Met + FH4)四氫葉酸供出甲基的主要途徑被阻斷 FH4 exist only in the form of N5-me

47、thyl FH4 “dangerous trap”(the reduction of N5,N10- methelene-FH4 to methyl FH4 is essentially irreversible, see P720).所以惡性貧血患者體內(nèi)的四氫葉酸主要以甲基四氫葉酸形式存在. 其它形式的四氫葉酸(如甲酰四氫葉酸)缺乏,使堿基(Pu, PyDNA,RNA)得不到一碳的供應(yīng),迅速周轉(zhuǎn)的紅細(xì)胞無法.Chapter291.(a)Glc+ATPG-6-P+(glycolysis)(b)G-6-P+2N+H2OR-5-P+2NH+2H+CO2 (PPP)(c)R-5-P+ATPPRPP+

48、(PRPP synthetase)total:2.(a)Gln+2ATCO3 carbamoylosate+2+Pi+Glu（）(b) carbamoylosate +AspN-carbamoylaspar（）(c) N-carbamoylaspareDHO+H2O（）(d)DHO+NAD+Oroe+NADH+H+（）total:3.(a)PRPP+Gln5-osoriyl-1-amine (P741)(b) carbamoylosate +AspN-carbamoylaspar(P746)(c) Oroe+PRPPOMP+PPi (P746)(d)Nicotinate+PRPPNicotin

49、ate ribonucleotide (P755)(e)Anthranilate鄰 氨 基 苯 甲 酸 +PRPP osoriyl-anthranilate 磷酸核糖鄰氨基苯甲酸 (P725)4.Azaserine 重氮絲氨酸 as anog of Gln inhibits the step 1 andstep4inPursynthesis(P742),PRPPandformylglycinamideribonucleotide 甲酰甘氨酰胺核苷酸 accumulated5.(a)Ser+FH4Gly+ methylene-FH4+H2O (P719)(b)dUMP+ methylene- F

50、H4dTMP+ FH2 (P752)H+H+FH4+N+(c) FH2+ N(P753)total:The price of methylation: besides AA , reducinger required6.the synthesis of folate is inhibited by sulfanilamide 葉酸被對(duì)氨基苯磺酰胺抑制 (as anog of p-aminobenzoate 對(duì)氨基苯甲酸, one of the precursors of folate) 加入對(duì)氨基苯甲酸使此抑制逆轉(zhuǎn)甲酰- FH4 缺乏inhibition of the step3 和 9he

51、Pursynthesis 甘氨酰胺核苷酸和 5-氨基咪唑 4-氨甲酰核苷酸積累細(xì)菌生長(zhǎng)被抑制.7（a）Gln+PRPP 5-osoriyl-1-amine (P741) Pu Nt(de novo synthesis)嘌呤從頭(b)hypoxanthine(Guanine)+ PRPP IMP(GMP)+PPi (P744)PuNt (salvage pathway)補(bǔ)救途徑嘌呤核苷酸(c)Oroe+PRPP OMP+PPi(P746) PyNt(denovosynthesis)嘧啶核苷酸從頭(d) Nicotinate+PRPPNicotinate ribonucleotide (P755)

52、 NAD+重要輔酶 NAD+的(e)ATP+PRPPosoriyl-ATPHis(：氨基酸)(f)Anthranilate 鄰氨基苯甲酸+PRPPosoriylanthranilateTrp (P725)必需氨基酸的9. Dj vu幻覺 the step 7 and 8 in Pu Nt synthesis (AspFum,a NH2 provided) (P742);similarly:he urea cycle: Cit+AspArginisuccinateArg+Fum (P635);also, IMP(P743)10. Pernicious anemia 惡性貧血(內(nèi)因子缺乏所致P64

53、4)VB12deficiencythe methyl transfer reaction blocked(HomoCys +N5- methyl FH4 -Met + FH4) 催化此反應(yīng)的酶以VB12 為輔酶 FH4existonlyintheformofN5-methylFH4 “dangerous trap”(the reduction of N5,N10- methelene -FH4tomethyl FH4 is essentially irreversible, P720).No formyl-FH4left for synthesis of Pu Nt11.(a)ADA(aden

54、osine 腺苷 deaminase 脫氨酶)-deficiency (fordeaminationofadenosineor2-deoxyadenosineP756) accumulation of adenosine or2-deoxyadenosineS-A homoCyshydrolase 水解酶 activity ismarked diminishedlevel of S-AhomoCys elevatedS-腺苷高半胱氨酸腺苷+高半胱氨酸(b)elevated level of S-A homoCysthe activated methyl cycleblocked (P722):

55、 S-A Met S-A homoCys + CH3theactivated methyl cyclocked12. cell A lacks thymidine kinase 胸苷激酶 （for: thymidine todTMP）cell B lacks HGPRT (for: Hypoxanthine or Guanine+PRPPIMP or GMP +PPi) 兩類細(xì)胞都是(節(jié)約利用途徑核苷酸缺陷的)突變型i.HATmedium(H:Hypoxanthine次 黃 嘌 呤 ;A:aminopterin or methotrexate 氨基蝶呤或氨甲蝶呤; T:thymine 胸腺嘧啶

56、)Cell A(胸苷酸補(bǔ)救利用途徑缺陷) : thymidine 胸(腺)苷dTMP (lacks thymidine kinase)dUMPdTMP (aminopterin or methotrexate)Cell B( 次黃嘌呤和鳥嘌呤補(bǔ)救利用途徑缺陷): nosalvage pathway for Pu synthesis (lacks HGPRT)No de novo pathway for Pu synthesis (no materials)CellC( 缺陷互補(bǔ) ):thymine(fromthemedium) thymidinedTMP(from cell B)PySynth

57、esis of IMP and GMP (HGPRT from cellA)Puii.cell A + plasmid (with the gene oferest and athymidine kinase gene)the only cellst will grow in a HAT medium are thoseve acquired a thymidine kinase gene.13. Adjunct therapy 輔助治療:ancer drugcell killed NAdegradationPu degradationuratehyperuricemia 高尿酸血treate

58、d by allopurinol15. G-6-Pase deficiency(糖原增加)GlcATP(肝細(xì)胞胞質(zhì)中) (降解)uratenormal people (by the ingestion of alcohol or by strenuousexercise) a lot of ATP consumedATP uratechapter30Liver contains G-6-Pase (so it can release Glc) and has no CoA transferase (so it can export the ketone body). Another diffe

59、rence: liver contains Glukokinase but no hexose kinase (thus only when there is high concentration of Glc does it take up Glc from blood)(a)GlcG-6-PDHAPglycerol-3-PTAGdeficiency of HK in adithe synthesis of TAGe tie woulderfere withglycogenG-6-PGlc (by G-6-Pase) export toblooddeficiency of G-6-Pase in liver glycogen in liver and blood Glcdeficiency of carnitine acyltransferaseimpairs theoxidationoflong-chainFA fastingandexerciseprecipie muscle crs(FA acyl-CoA acyl-carnitine transmembraneo Mitoacyl-carniti