血液生物化學(xué)

1、第二十一章 血液生物化學(xué)（Blood Biochemistry ）重慶醫(yī)科大學(xué)生物化學(xué)教研室曾昭淳,圖1 血清蛋白醋酸纖維素薄膜電泳結(jié)果,左邊接負(fù)極，右邊接正極。在pH8.6的巴比妥緩沖液中，蛋白質(zhì)帶負(fù)電荷，向正極移動(dòng)。各蛋白帶已注明。清蛋白染色最深，泳動(dòng)的距離最長(zhǎng)，?-球蛋白的帶最寬，泳動(dòng)的距離最短。,血液凝固途徑,血液凝固的外源性途徑,外源性途徑是組織因子（TF）進(jìn)入血液，引起因子VII的活化并形成VII-Ca2+-T

2、F復(fù)合物，激活因子X，凝血酶原，催化纖維蛋白原形成纖維蛋白，這是體內(nèi)主要的凝血途徑。,內(nèi)源性凝血途徑不是體內(nèi)主要的凝血途徑。通常是因?yàn)檠軆?nèi)皮損傷所引起，常常是病理現(xiàn)象。抽出的血液也會(huì)凝固，通常是通過與玻璃管壁接觸，而啟動(dòng)內(nèi)源性凝血途徑。,內(nèi)源性凝血途徑,凝血因子VIII膜結(jié)合結(jié)構(gòu)域的結(jié)構(gòu),人類抗凝血酶III的結(jié)構(gòu),因子X肽鏈骨架在空間的走向,N為肽鏈的氨末端，C為肽鏈的羧末端。圖中粗線部分代表EGF樣結(jié)構(gòu)域。,因子VIIa的蛋白酶

3、結(jié)構(gòu)域的條帶結(jié)構(gòu),活性中心的底物結(jié)合口袋由H（代表193位His）、S（代表344位Ser）、D（代表338位Asp）構(gòu)成。TF inhibitory peptide代表結(jié)合組織因子的區(qū)域。PN~P`N區(qū)域?yàn)閿U(kuò)大的底物結(jié)合區(qū)。E210和E220（代表210位和220位的Glu）是鈣離子結(jié)合部位。,從cDNA推導(dǎo)的TF肽鏈氨基酸順序,TF是一個(gè)跨膜蛋白質(zhì)，其N-末端在細(xì)胞外，1~219氨基酸殘基構(gòu)成胞外結(jié)構(gòu)域；220~242氨基酸殘基構(gòu)成

4、跨膜結(jié)構(gòu)域；羧末端的21氨基酸殘基構(gòu)成胞液結(jié)構(gòu)域。,含?-羧基谷氨酸的蛋白質(zhì)共同的結(jié)構(gòu)特點(diǎn),,N-末端為含?-羧基谷氨酸殘基的區(qū)域；羧末端為絲氨酸蛋白酶結(jié)構(gòu)域；EGF代表與表皮生長(zhǎng)因子類似的結(jié)構(gòu)域。酶解激活部位通常在形成二硫鍵的兩個(gè)半胱氨酸之間某個(gè)氨基酸殘基形成的肽鍵。,含?-羧基谷氨酸酶原結(jié)構(gòu)及酶解部位,圖中箭頭表示酶解部位，數(shù)字代表氨基酸的位置。凝血酶原第二個(gè)水解部位在二硫鍵外的區(qū)域，結(jié)果?-羧基谷氨酸殘基被切除，不再保留在凝血酶內(nèi)

5、。水解因子VII Arg152-Ile153之間的肽鍵而激活它。水解因子IX的Arg145和Arg180 組成的肽鍵，釋放出分子量大約11 000的肽段，而激活它。因子X含一條輕鏈和一條重鏈，二者通過二硫鍵連接，水解重鏈的Arg194-Ile195之間的肽鍵可激活它。蛋白C也含通過二硫鍵連接一條輕鏈和一條重鏈，水解重鏈的Arg169-Ile170之間的肽鍵可激活它。,凝血酶原激活示意圖,凝血酶原的320位精氨酸羧基側(cè)肽鍵首先被酶解，生成

6、的兩個(gè)肽段由原有的二硫鍵連接。隨后284位精氨酸羧基側(cè)肽鍵被酶解，生成由原有的二硫鍵連接的A肽和B肽的、有活性的?-凝血酶并釋放F1.2肽段。,纖維蛋白原分子結(jié)構(gòu)示意圖,纖維蛋白原分子由?、?、?肽鏈各兩條組成?？臻g結(jié)構(gòu)似兩個(gè)棒形區(qū)連接三個(gè)球形區(qū)。中間一個(gè)球形區(qū)內(nèi)，通過二硫鍵將?、?、?各條肽鏈共價(jià)連接在一起,纖維蛋白原形成血凝塊,,纖維蛋白原被凝血酶水解釋放出兩個(gè)A肽和兩個(gè)B肽，形成可溶性纖維蛋白單體。纖維蛋白單體聚集成纖維蛋白軟凝塊

7、，再由XIIIa催化纖維蛋白單體之間共價(jià)交聯(lián)，形成血凝塊。,纖維蛋白單體之間的交聯(lián)反應(yīng),血小板在凝血過程中的作用,凝血調(diào)理素的功能,凝血調(diào)理素與凝血酶形成復(fù)合物，使凝血酶水解纖維蛋白原的活性轉(zhuǎn)變成酶解激活蛋白C的活性，活化的蛋白C在輔助因子蛋白S 的協(xié)助下，滅活因子VIIIa和因子XIIIa，使凝血酶的作用由促進(jìn)凝血轉(zhuǎn)變成抗凝血。,溶纖酶水解纖維蛋白的作用,TFPI的結(jié)構(gòu),圖中有三個(gè)球形的結(jié)構(gòu)域， 結(jié)構(gòu)域1抑制VIIa， 結(jié)構(gòu)域2抑

8、制Xa，結(jié)構(gòu)域3是胞吞TFPI、VIIa、Xa 與TF形成的復(fù)合物所必需。箭頭表示每個(gè)結(jié)構(gòu)域的活性部位。,假定的組織因子途徑抑制機(jī)制,TFPI、Xa、VIIa與細(xì)胞膜上的TF形成復(fù)合物。抑制了Va、XIIa的活性，且Va、XIIa 隨后被胞吞降解。,2,3-二磷酸甘油酸支路,2,3-二磷酸甘油酸支路是糖酵解途徑的一條支路.由3-磷酸甘油變位酶催化1,3-二磷酸甘油酸生成2,3-二磷酸甘油酸,再由2,3-二磷酸甘油酸磷酸酶催化生成3-磷

9、酸甘油酸,回到糖酵解途徑.,,2,3-DPG與血紅蛋白的結(jié)合,2,3-DPG可以進(jìn)入Hb分子4個(gè)亞基的對(duì)稱中心的孔穴內(nèi)，與其結(jié)合。它帶的負(fù)電荷與組成孔穴側(cè)壁的2個(gè)亞基上的正電荷基團(tuán)形成鹽鍵。使Hb的構(gòu)象更加穩(wěn)定，降低Hb與O2的親和力。,2,3-DPG與血紅蛋白的結(jié)合,,血紅素的結(jié)構(gòu),δ-氨基γ-酮戊酸(ALA)的生成,膽色素原的生成,,,線狀四吡咯的生成4分子膽色素原在尿卟啉原同合酶I的作用下,生成線狀四吡咯,,,尿卟啉原III的

10、生成線狀四吡咯在由尿卟啉原III同合酶催化生成生成尿卟啉原III,糞卟啉原III生成尿卟啉原III在脫羧酶催化下，卟啉環(huán)上的1、3、5、8位置上的4個(gè)乙?；擊绒D(zhuǎn)變成甲基，尿卟啉原III就轉(zhuǎn)變成糞卟啉原III,原卟啉原IX生成,糞卟啉原III在酶的催化下脫氫氧化生成原卟啉原IX。原卟啉原IX與糞卟啉原III的區(qū)別在于2、4兩個(gè)位置上的丙酸基氧化脫羧成乙酰基。.,原卟啉IX的生成,原卟啉原IX中連接四個(gè)吡咯環(huán)的甲烯基脫氫氧化成甲炔

11、基。四個(gè)吡咯環(huán)N原子上的氫脫掉兩個(gè)。,血紅素的生成,原卟啉IX與Fe 2+螯合，生成血紅素。,血紅素合成的全過程,高鐵血紅素的作用,高鐵血紅素抑制cAMP變構(gòu)激活A(yù)激酶，抑制了eIF－2激酶的磷酸化，保持在無活性狀態(tài)，使 eIF－2不能被磷酸化，保持持續(xù)的活性狀態(tài)，促進(jìn)蛋白質(zhì)的合成。因而也促進(jìn)血紅蛋白的合成。,血紅蛋白的氧飽和曲線,2,3－DPG對(duì)氧飽和曲線的影響,2,3－DPG在紅細(xì)胞中的濃度越高，血紅蛋白的氧飽和曲線越左移。達(dá)到50

12、％氧飽和度所需要的氧分壓越低。在肺部，氧分壓高血紅蛋白與氧的結(jié)合不受影響，在組織氧分壓低但氧合血紅蛋白能釋放更多的氧,pH對(duì)氧飽和曲線的影響,血液的pH增高，氧飽和曲線左移，血液的pH降低，氧飽和曲線右移。,溫度對(duì)氧飽和曲線的影響,溫度降低，血紅蛋白氧飽和曲線左移，溫度升高，血紅蛋白氧飽和曲線右移。,組織細(xì)胞產(chǎn)生的二氧化碳進(jìn)入經(jīng)血液進(jìn)入紅細(xì)胞后的變化,第21章 血液生化選擇題,,1、在血凝塊的形成中：,A 從纖維蛋白原形成纖維蛋白，蛋白

13、酶解?-羧基谷氨酸殘基是必需的。B 通過因子XIII的轉(zhuǎn)谷氨酰胺酶作用，纖維蛋白分子之間的交連穩(wěn)定血凝塊。C 凝血酶惟一的作用是激活因子VII。D 凝血過程開始時(shí)，因子III，即組織因子必需被滅活。E 鈣離子的主要作用是結(jié)合纖維蛋白分子，聚集它們形成血凝塊,2、轉(zhuǎn)變凝血酶原成凝血酶必需的因子Xa ，通過復(fù)合物TF-VII-Ca2+作用于因子X而形成。,A 只存在于凝血的外源性途徑B 只存在于凝血的內(nèi)源性途徑C

14、 既是內(nèi)源性途徑也是外源性途徑的一部分D 只有當(dāng)正常的凝血‘瀑布’效應(yīng)被抑制時(shí)，才會(huì) 發(fā)生。E 當(dāng)出現(xiàn)纖溶時(shí)才會(huì)發(fā)生。,3、纖維蛋白凝塊的溶解,A 和血凝塊的形成平衡B 當(dāng)溶纖酶結(jié)合于血凝塊時(shí)才開始C 需要水解溶纖酶原形成輕鏈和重鏈D 蛋白酶抑制劑對(duì)溶纖酶原的作用可調(diào)節(jié)E 需要組織溶纖酶激活劑轉(zhuǎn)換溶纖酶原成 溶纖酶。,4、血小板的聚集,A 在損傷部位通過轉(zhuǎn)

15、變纖維蛋白原成纖維蛋白而啟動(dòng)B 在未損傷的血管，由完整的內(nèi)皮細(xì)胞分泌PGG2而抑制。C 引起形態(tài)學(xué)的變化和釋放血管舒張劑血清素D 通過釋放ADP和thromboxaneA2 而被抑制E 被vWF抑制。,5 因子XIII激活后是,A蛋白水解酶 B酶的輔助因子 C蛋白酶的抑制劑 D蛋白酶的激活劑 E轉(zhuǎn)谷氨酰胺酶,6 血漿清蛋白,A在生理pH條件下，帶凈電荷為正。B用5

16、0%硫酸銨把它從血清沉淀下來。C能結(jié)合并運(yùn)輸維生素A 。D維持血漿膠體滲透壓，在毛細(xì)血管靜 脈側(cè)，水分從血管流入組織。 E它既能結(jié)合金屬離子，也能結(jié)合有機(jī)陰離子。,7 維生素K稱為凝血維生素是因?yàn)?A 促進(jìn)肝合成的凝血因子 II、V、IX、X的谷氨酸殘基的?-羧化。 B 促進(jìn)肝合成的凝血因子II 、 VII 、 IX、X 的谷氨酸殘基?-羧化。 C 促進(jìn)肝合成的凝血因子III、 VII、VIII、

17、IX、 谷氨酸殘基?-羧化。 D 促進(jìn)肝合成的凝血因子III、VII、IX、X、 谷氨酸殘基?-羧化。 E 促進(jìn)肝合成的凝血因子II、VIII、IX、 XIII谷氨酸殘基?-羧化。,8、下列哪種蛋白運(yùn)輸血漿中游離的脂肪酸,A運(yùn)鐵蛋白 B銅藍(lán)蛋白 C清蛋白 D結(jié)合珠蛋白 E ?1-酸性糖蛋白D,9、肝功能受到損壞后受到影響較輕的是,A纖維蛋白原 B因子VIII 、V、X C 血漿清蛋白 D 凝

18、血酶原 E 因子XIII,,10、血液中運(yùn)輸CO2的主要形式是,A 溶解在血液中的 HCO3- B 紅細(xì)胞內(nèi)氨基甲酸血紅蛋白 C 溶解在血液中的CO2 D 與血漿蛋白結(jié)合CO2 ECaCO3,11、合成血紅素的基本原料是,A 乙酰輔酶A、Fe2+B 琥珀酰輔酶A、 Fe2+C 甘氨酸、琥珀酰輔酶AD 甘氨酸、 Fe

19、2+E 甘氨酸、琥珀酰輔酶A、Fe2+,12、血紅素合成的限速酶是,AALA合酶 BALA脫水酶 C膽色素原脫氨酶 D尿卟啉原III氧化脫羧酶 E亞鐵螯合酶。,13、存在于成熟紅細(xì)胞的代謝有,A糖的異生 B脂肪酸合成 C磷酸戊糖途徑 D 酮體合成 E 氧化磷酸化,14、ALA合成酶,A受血紅素的變構(gòu)抑制 B受高鐵血紅素的變構(gòu)

20、激活 C受血紅蛋白的變構(gòu)激活 D受睪丸素5-??還原物的阻遏 EEPO促進(jìn)其活性,15 關(guān)于2，3-二磷酸甘油酸，正確地是：,A 主要是由 3- 磷酸甘油酸生成 B 分子在生理?xiàng)l件下帶有6個(gè)負(fù)電荷C 能于血紅蛋白的?-亞基通過鹽鍵結(jié)合D 血紅蛋白與它結(jié)合后，氧飽和曲線向右 移。 E 平原地區(qū)生活的人紅細(xì)胞的含量比在高原地區(qū)生活的人紅細(xì)胞的含量高。,16 凝血酶原激活物是

21、,AIIIa-Ca2+-Va BIXa -Ca2+-Va CVIIa -Ca2+-Va DXa -Ca2+-Va EVIIa -Ca2+- IIIa,17 血液中非蛋白N含量最多的物質(zhì)是,A肌酸 B肌酐 C尿酸 D 尿素 E小分子肽,18 紅細(xì)胞內(nèi)最主要的抗氧化物質(zhì)是,A NADH+H+ B

22、 FMNH2 C FADH2 D GSH E HbH2,19 凝血因子XIII,A 是一個(gè)蛋白酶，可水解因子X B 是凝血酶原激活物的輔助因子 C 抑制血漿中抗凝血因子的活性 D 催化在纖維蛋白之間形成異肽鍵 E 抑制血漿中溶纖酶的活性,20、既是蛋白酶的底物，激活后又作酶的輔助因子的凝血因子是,A 因子VIII

23、 B 因子VII C 因子IX D 因子XII E 因子III,21、不參與接觸活化的凝血因子有,A 因子VII B 因子XII C 因子XI D 高分子激肽原 E 激肽釋放酶原,1題 答案,答案A 錯(cuò)誤答案B 正確。凝血過程中，凝血酶催化纖維蛋白原轉(zhuǎn)變成纖維蛋白，因子V、VIII、XIII也對(duì)凝血酶敏感。因子XIII的轉(zhuǎn)谷氨酰胺酶作用，催

24、化纖維蛋白分子之間的交連，形成穩(wěn)定血凝塊。因子III即組織因子是激活外源性凝血途徑必需的。鈣離子在凝血過程中參與凝血因子與血小板磷脂之間的‘搭橋’作用。答案C錯(cuò)誤答案D錯(cuò)誤答案E錯(cuò)誤,2題 答案,答案A正確。TF-VII-Ca2+作用于因子X生成Xa是外源性途徑的一步反應(yīng)，它不出現(xiàn)在內(nèi)源性凝血途徑，也不出現(xiàn)在內(nèi)、外源途徑的共同部分。更不是纖溶過程的反應(yīng)。答案B 錯(cuò)誤答案C 錯(cuò)誤答案D 錯(cuò)誤答案E 錯(cuò)誤,3題 答案,答案

25、A 錯(cuò)誤 答案 B 錯(cuò)誤答案 C 錯(cuò)誤答案 D 錯(cuò)誤答案 E 正確 溶解纖維蛋白需要溶纖酶的作用，溶纖酶原本來就含有通過二硫鍵連接的一條重鏈和一條輕鏈。溶纖酶原在組織溶纖酶激活劑或尿激酶的作用下，暴露或形成酶的活性中心，轉(zhuǎn)變成溶纖酶。,4題 答案,答案A 錯(cuò)誤答案 B 錯(cuò)誤答案 C 正確血小板的積聚，引起血小板形態(tài)上的改變，釋放血清素， ADP、某些類型的磷脂和蛋白質(zhì)，有助于血液的凝固和損傷組織的修復(fù)。 答案

26、D 錯(cuò)誤答案 E 錯(cuò)誤,5題 答案,答案 A 錯(cuò)誤 答案 B 錯(cuò)誤答案 C 錯(cuò)誤答案 D 錯(cuò)誤答案 E 正確因子XIII 是轉(zhuǎn)谷氨酰胺酶原，激活后成谷氨酰氨酶，催化可溶性纖維蛋白形成異肽鍵相連。形成纖維蛋白網(wǎng)。,6題 答案,答案 A 錯(cuò)誤答案 B 錯(cuò)誤答案 C 錯(cuò)誤答案 D 錯(cuò)誤答案 E 正確 前清蛋白可以結(jié)合游離脂肪酸，膽紅素等小分子有機(jī)化合物，也能結(jié)合鈣離子。,7題 答案,答案 A 錯(cuò)誤答案 B 正確 因子I

27、I、VII、IX、X肽鏈合成后，其谷氨酸殘基需要進(jìn)行?-羧化修飾，才具有凝血活性，維生素K是谷氨酸?-羧化酶的輔助因子。答案 C 錯(cuò)誤答案 D 錯(cuò)誤答案 E 錯(cuò)誤,8題 答案,答案 A 錯(cuò)誤答案 B 錯(cuò)誤答案 C 正確血漿中的游離脂肪酸是與血漿中的清蛋白結(jié)合而運(yùn)輸。答案 D 錯(cuò)誤答案 E 錯(cuò)誤,9題 答案,答案 A 錯(cuò)誤。答案 B 錯(cuò)誤。答案 C 錯(cuò)誤。答案 D 錯(cuò)誤。答案 E 正確。纖維蛋白原、因子VIII 、

28、V、X、 血漿清蛋、凝血酶原均在肝合成，故肝功能受到損壞后受到的影響較大。因子XIII不在肝合成肝功能受到損壞后受到影響較輕。,10題 答案,答案 A正確: 溶解在血液中的 HCO3- ,溶解在血液中的 HCO3- ，占血液運(yùn)輸CO2的88%，是血液運(yùn)輸CO2主要形式。答案 B 錯(cuò)誤答案 C 錯(cuò)誤答案 D 錯(cuò)誤答案 E 錯(cuò)誤,11題 答案,答案A 錯(cuò)誤。答案B 錯(cuò)誤。答案C 錯(cuò)誤。答案D 錯(cuò)誤。答案E 正確。合成血紅素的

29、基本原料是甘氨酸、琥珀酰輔酶A、Fe2+。,12題 答案,答案 A 正確。血紅素合成的限速酶是ALA合酶。該酶催化琥珀酰輔酶A和甘氨酸反應(yīng)生成ALA。答案 B 錯(cuò)誤。答案 C 錯(cuò)誤。答案 D 錯(cuò)誤。答案 E 錯(cuò)誤。,13題 答案,答案 A 錯(cuò)誤。答案 B 錯(cuò)誤。答案 C 正確。酮體合成和氧化磷酸化是在限粒體內(nèi)進(jìn)行，成熟的紅細(xì)胞沒有線粒體，故不能進(jìn)行酮體合成和氧化磷酸化。成熟的紅細(xì)胞不能從頭合成脂肪酸，也不能合成糖原，但可以進(jìn)

30、行糖酵解和磷酸戊糖途徑。答案 D 錯(cuò)誤。答案 E 錯(cuò)誤。,14題 答案,答案 A 正確。血紅素合成可受多種因素的調(diào)節(jié)，但ALA合酶是血紅素合成的限速酶,主要受血紅素的反饋抑制。答案 B 錯(cuò)誤答案 C錯(cuò)誤答案 D錯(cuò)誤答案 E 錯(cuò)誤,15題 答案,答案 A 錯(cuò)誤 答案 B 錯(cuò)誤答案 C 錯(cuò)誤答案 D 正確2,3－DPG由1,3DPG生成，在生理?xiàng)l件下分子帶5個(gè)負(fù)電荷，可進(jìn)入血紅蛋白中心孔隙，與?－亞基帶的正電荷生成鹽鍵，它

31、與血紅蛋白結(jié)合后，使血紅蛋白的氧飽和曲線向右移，氧合血紅蛋白釋放更多的氧。高原地區(qū)生活的人，紅細(xì)胞的 2,3－DPG含量比平原地區(qū)生活的人高。答案 C 錯(cuò)誤,16題 答案,答案 A 錯(cuò)誤 答案 B 錯(cuò)誤。答案 C 錯(cuò)誤。答案 D 正確。無論凝血的內(nèi)源性或外源性途徑，都需要形成Xa -Ca2+-Va，即凝血酶原激活物，激活凝血酶原，生成凝血酶。答案 E 錯(cuò)誤。,17題 答案,答案 A 錯(cuò)誤 答案 B 錯(cuò)誤。答案 C 錯(cuò)誤。

32、答案 D 正確。血液中的非蛋白類含氮化合物主要有尿素、肌酸、肌苷、尿酸、膽紅素和氨等，它們含的氮總稱非蛋白氮，其中血尿素氮約占NPN的1/2。答案E正確。,18題 答案,答案 A 錯(cuò)誤 答案 B 錯(cuò)誤。答案 C 錯(cuò)誤。答案 D 正確。GSH是紅細(xì)胞內(nèi)最主要的抗氧化物質(zhì)，它被氧化后生成GSSG，GSSG可由NADPH提供H，在谷胱甘肽還原酶的催化下，還原成GSH。GSH的氧化可以保護(hù)紅細(xì)胞內(nèi)的蛋白質(zhì)、酶、膜脂質(zhì)免受氧化損傷。答案

33、E正確。,19題 答案,答案 A 錯(cuò)誤 答案 B 錯(cuò)誤。答案 C 錯(cuò)誤。答案 D 正確。因子XIII是一個(gè)酶原，被酶解激活后，是生成轉(zhuǎn)谷氨酰胺酶，催化在纖維蛋白之間形成異肽鍵，即谷氨酰胺殘基與賴氨酸的?氨基之間生成異肽鍵。 答案 E 正確。,20題 答案,答案 A 正確。因子VIII被酶解激活后，生成VIIIa，與因子IXa生成1:1的復(fù)合物，作為IXa的輔助因子,激活因子X。答案B錯(cuò)誤。答案C錯(cuò)誤。答案D錯(cuò)誤。答案E錯(cuò)

34、誤。,21題 答案,答案 A 正確。接觸活化途徑即內(nèi)源性途徑。因子VII參與外源性途徑凝血過程，但又不參與兩條途徑的共同部分。答案B 錯(cuò)誤。答案C 錯(cuò)誤。答案D 錯(cuò)誤。答案E 錯(cuò)誤。,Hans Fischer – BiographyKarl Landsteiner – Biography,,,Hans Fischer was born in July 27, 1881 at Hoechst, on the river Mai

35、n, in Germany. His father was Dr. Eugen Fischer, Director of the firm of Kalle & Co, Wiesbaden, and Privatdozent at the Technical High School, Stuttgart; his mother was Anna Herdegen. He went to a primary school in S

36、tuttgart, and later to the "humanistische Gymnasium" (grammar school with emphasis on the classics) in Wiesbaden,,,matriculating in 1899. He read chemistry and medicine simultaneously, first at the University o

37、f Lausanne and then at Marburg. He obtained his chemistry degree under T. Zincke at Marburg in 1904; two years later, in 1906, a licence for medicine was conferred on him at Munich. In 1908 he qualified for his M.D. unde

38、r F. von Müller, also at Munich.,,Fischer spent his first working years at the Second Medical Clinic in Munich and at the First Berlin Chemical Institute under Emil Fischer. He returned to Munich in 1911 and qualifi

39、ed as lecturer on internal medicine one year later. In 1913 he was appointed E.F. Weinland's successor at the Physiological Institute (O. Frank) in Munich, where he became a lecturer on physiology. In 1916 Fischer fo

40、llowed the invitation of the University of Innsbruck to succeed Windaus as Professor of Medical Chemistry; from there he went to the University of Vienna in 1918.,,From April 1, 1921 until his death he held the position

41、of Professor of Organic Chemistry at the Technische Hochschule (Technical University) in Munich, as successor to Wieland.,,Fischer's scientific work was mostly concerned with the investigation of the constitutive pro

42、perties of the pigments in blood, bile, and also leaves, as well as with the chemistry of pyrrole. The main reason for the latter investigation was the synthesis of these natural pyrrole pigments. Of special importance w

43、as his synthesis of bilirubin. His numerous papers were mostly published in Liebigs Annalen der Chemie and Hoppe-Seylers Zeitschrift für physiologische Chemie.,,In recognition of his work in these fields, the title

44、of a "Geheimer Regierungsrat" (Privy Councillor) was conferred upon Hans Fischer in 1925; in 1929 he was awarded the Liebig Memorial Medal; Harvard University bestowed the title of honorary doctor on him in 193

45、6; he received the Davy Medal in 1937. Fischer received the greatest honour of all, the Nobel Prize for 1930, for his work on the chemistry of pyrrole and the synthesis of haemin. In 1935, Professor Fischer married Wiltr

46、ud Haufe. He died on March 31, 1945 in Munich.,Karl Landsteiner – Biography,Karl Landsteiner was born in Vienna on June 14, 1868. His father, Leopold Landsteiner, a doctor of law, was a well-known journalist and newspa

47、per publisher, who died when Karl was six years old. Karl was brought up by his mother, Fanny Hess, to whom he was so devoted that a death mask of her hung on his wall until he died. After leaving school, Landsteiner stu

48、died medicine at the Univerisity of Vienna, graduating in 1891.,,Even while he was a student he had begun to do biochemical research end in 1891 he published a paper on the influence of diet on the composition of blood a

49、sh. To gain further knowledge of chemistry he spent the next five years in the laboratories of Hantzsch at Zurich, Emil Fischer at Wurzburg, and E. Bamberger at Munich.,,Returning to Vienna, Landsteiner resumed his medic

50、al studies at the Vienna General Hospital. In 1896 he became an assistant under Max von Gruber in the Hygiene Institute at Vienna. Even at this time he was interested in the mechanisms of immunity and in the nature of an

51、tibodies. From 1898 till 1908 he held the post of assistant in the University Department of Pathological Anatomy in Vienna, the Head of which was Professor A. Weichselbaum, who had discovered the bacterial cause of menin

52、gitis, and with Fraenckel had discovered the pneumococcus.,,Here Landsteiner worked on morbid physiology rather than on morbid anatomy. In this he was encouraged by Weichselbaum, in spite of the criticism of others in th

53、is Institute. In 1908 Weichselbaum secured his appointment as Prosector in the Wilhelminaspital in Vienna, where he remained until 1919. In 1911 he became Professor of Pathological Anatomy in the University of Vienna, bu

54、t without the corresponding salary.,,Up to the year 1919, after twenty years of work on pathological anatomy, Landsteiner with a number of collaborators had published many papers on his findings in morbid anatomy and on

55、immunology. He discovered new facts about the immunology of syphilis, added to the knowledge of the Wassermann reaction, and discovered the immunological factors which he named haptens (it then became clear that the acti

56、ve substances in the extracts of normal organs used in this reaction were, in fact, haptens). He made fundamental contributions to our knowledge of paroxysmal haemoglobinuria.,,He also showed that the cause of poliomyeli

57、tis could be transmitted to monkeys by injecting into them material prepared by grinding up the spinal cords of children who had died from this disease, and, lacking in Vienna monkeys for further experiments, he went to

58、the Pasteur Institute in Paris, where monkeys were available. His work there, together with that independently done by Flexner and Lewis, laid the foundations of our knowledge of the cause and immunology of poliomyelitis

59、.,,Landsteiner made numerous contributions to both pathological anatomy, histology and immunology, all of which showed, not only his meticulous care in observation and description, but also his biological understanding.

60、But his name will no doubt always be honoured for his discovery in 1901 of, and outstanding work on, the blood groups, for which he was given the Nobel Prize for Physiology or Medicine in 1930.,,In 1875 Landois had repor

61、ted that, when man is given transfusions of the blood of other animals, these foreign blood corpuscles are clumped and broken up in the blood vessels of man with the liberation of haemoglobin. In 1901-1903 Landsteiner po

62、inted out that a similar reaction may occur when the blood of one human individual is transfused, not with the blood of another animal, but with that of another human being, and that this might be the cause of shock, jau

63、ndice, and haemoglobinuria that had followed some earlier attempts at blood transfusions.,,His suggestions, however, received little attention until, in 1909, he classified the bloods of human beings into the now well-kn

64、own A, B, AB, and O groups and showed that transfusions between individuals of groups A or B do not result in the destruction of new blood cells and that this catastrophe occurs only when a person is transfused with the

65、blood of a person belonging to a different group. Earlier, in 1901-1903, Landsteiner had suggested that, because the characteristics which determine the blood groups are inherited, the blood groups may be used to decide

66、instances of doubtful paternity.,,Much of the subsequent work that Landsteiner and his pupils did on blood groups and the immunological uses they made of them was done, not in Vienna, but in New York. For in 1919 conditi

67、ons in Vienna were such that laboratory work was very difficult and, seeing no future for Austria, Landsteiner obtained the appointment of Prosector to a small Roman Catholic Hospital at The Hague. Here he published, fro

68、m 1919-1922, twelve papers on new haptens that he had discovered, on conjugates with proteins which were capable of inducing anaphylaxis and on related problems, and also on the serological specificity of the haemoglobin

69、s of different species of animals.,,His work in Holland came to an end when he was offered a post in the Rockefeller Institute for Medical Research in New York and he moved there together with his family. It was here tha

70、t he did, in collaboration with Levine and Wiener, the further work on the blood groups which greatly extended the number of these groups, and here in collaboration with Wiener studied bleeding in the new-born, leading t