生物化學(xué)教學(xué)課件：生化引論

1、1 現(xiàn)代化大學(xué)現(xiàn)代化大學(xué): : 培養(yǎng)科學(xué)思維和創(chuàng)新人才培養(yǎng)科學(xué)思維和創(chuàng)新人才 創(chuàng)造知識(shí)，社會(huì)發(fā)展的原動(dòng)力創(chuàng)造知識(shí)，社會(huì)發(fā)展的原動(dòng)力 科學(xué)研究科學(xué)研究: 凝練和提出問題凝練和提出問題 (思維思維) 如何去解決問題如何去解決問題 (人、經(jīng)費(fèi)、實(shí)驗(yàn)條件人、經(jīng)費(fèi)、實(shí)驗(yàn)條件) 你的成果如何得到社會(huì)的承認(rèn)你的成果如何得到社會(huì)的承認(rèn) (回報(bào)回報(bào)) 如何做好這些？首先是打好基礎(chǔ)如何做好這些？首先是打好基礎(chǔ) 2 Diversity and Unity For the discovery that mature cells can be reprogrammed to become pluripotent “發(fā)現(xiàn)

2、成熟細(xì)胞可以重新編程而獲得多能性發(fā)現(xiàn)成熟細(xì)胞可以重新編程而獲得多能性” Shinya Yamanaka John B. Gurdon 2012年，諾貝爾生理年，諾貝爾生理/醫(yī)學(xué)獎(jiǎng)醫(yī)學(xué)獎(jiǎng) 中樞神經(jīng)中樞神經(jīng) 軟骨軟骨 肌肉肌肉 脂肪脂肪 上皮上皮 畸胎瘤實(shí)驗(yàn)畸胎瘤實(shí)驗(yàn) iPS-derived mice 引入關(guān)鍵基因引入關(guān)鍵基因 體細(xì)胞重新編程體細(xì)胞重新編程 iPS, induced pluripotent stem cell 誘導(dǎo)多能干細(xì)胞誘導(dǎo)多能干細(xì)胞 iMice Robert J. Lefkowitz Brian K. Kobilka “for studies of G-protein-cou

3、pled receptors” 表彰他們對(duì)表彰他們對(duì)G蛋白耦聯(lián)受體的研究蛋白耦聯(lián)受體的研究 人高度緊張時(shí)人高度緊張時(shí)“腎上腺素開始大量分泌腎上腺素開始大量分泌” 2012年，諾貝爾年，諾貝爾 化學(xué)獎(jiǎng)化學(xué)獎(jiǎng) How could the inside of the cell know what was happening on the outside? 腦腦：神經(jīng)信號(hào)警告神經(jīng)信號(hào)警告 身體各部位，釋放身體各部位，釋放 激素激活腎上腺激素激活腎上腺 眼：眼：瞳孔瞳孔 放大，視放大，視 野變窄野變窄 心臟心臟：心率加速心率加速 肺：肺：氣管擴(kuò)張，氣管擴(kuò)張， 呼吸頻率加快呼吸頻率加快 肌肉：肌肉：血量增

4、加，血量增加， 肌肉收縮肌肉收縮 肝臟：肝臟：糖原分解，糖原分解， 糖被釋放到血液糖被釋放到血液 脂肪細(xì)胞：脂肪細(xì)胞：脂肪脂肪 酸被釋放到血液酸被釋放到血液 腸胃：腸胃：流入消化流入消化 系統(tǒng)的血量減少系統(tǒng)的血量減少 Time to flee! 髓質(zhì)髓質(zhì) 皮質(zhì)醇皮質(zhì)醇 腎上腺素腎上腺素 去甲腎上腺素去甲腎上腺素 皮質(zhì)皮質(zhì) 7 G蛋白耦聯(lián)受體：蛋白耦聯(lián)受體： 感受物化刺激，包括多種神經(jīng)遞質(zhì)、肽類激感受物化刺激，包括多種神經(jīng)遞質(zhì)、肽類激 素和趨化因子受體素和趨化因子受體 超過半數(shù)的現(xiàn)代藥物靶向超過半數(shù)的現(xiàn)代藥物靶向 8 英國細(xì)菌學(xué)家弗萊明英國細(xì)菌學(xué)家弗萊明 - 1928- 1928年發(fā)現(xiàn)青霉素年發(fā)

5、現(xiàn)青霉素 弗萊明在簡(jiǎn)陋的實(shí)驗(yàn)室，研究葡萄球菌弗萊明在簡(jiǎn)陋的實(shí)驗(yàn)室，研究葡萄球菌 蓋子沒蓋好蓋子沒蓋好，培養(yǎng)細(xì)菌的瓊脂上附了一層青霉菌，培養(yǎng)細(xì)菌的瓊脂上附了一層青霉菌 ( (來自樓上的一位研究青霉菌學(xué)者的窗口來自樓上的一位研究青霉菌學(xué)者的窗口) ) 在青霉菌的近旁，葡萄球菌不見了在青霉菌的近旁，葡萄球菌不見了 培養(yǎng)這種霉菌，發(fā)現(xiàn)青霉素可快速殺死將葡萄球菌培養(yǎng)這種霉菌，發(fā)現(xiàn)青霉素可快速殺死將葡萄球菌 發(fā)明了第一種能夠治療人類疾病的抗生素發(fā)明了第一種能夠治療人類疾病的抗生素- -青霉素青霉素 也有的藥物：有一定作用也有的藥物：有一定作用 但其副作用是人類但其副作用是人類付出巨大代價(jià)付出巨大代價(jià)之后才

6、了解之后才了解 9 Thalidomide：人類藥物史：人類藥物史 上的著名案例，其出名不上的著名案例，其出名不 是因?yàn)樗幬锆熜?，而是毒是因?yàn)樗幬锆熜?，而是?性性-“海豹胎事件海豹胎事件” 沙利度胺沙利度胺 (Thalidomide)： 手性化合物手性化合物 R-R-構(gòu)型：抑制妊娠反應(yīng)；構(gòu)型：抑制妊娠反應(yīng)；S- S-構(gòu)型有致畸性構(gòu)型有致畸性 手性藥物：手性藥物：1990年銷售額年銷售額 180億，億，2005年年-1720億美元億美元 2006年全球暢銷藥物的前四名均為單旋體手性藥物年全球暢銷藥物的前四名均為單旋體手性藥物 沙利度胺的新認(rèn)識(shí)：沙利度胺的新認(rèn)識(shí)： 在免疫、抗炎、抗血管生成的藥理

7、和一些疑難病癥上在免疫、抗炎、抗血管生成的藥理和一些疑難病癥上 的研究和治療應(yīng)用中取得了令人欣喜的結(jié)果的研究和治療應(yīng)用中取得了令人欣喜的結(jié)果 11 生物化學(xué)是生物學(xué)和醫(yī)學(xué)研究的必備基礎(chǔ)生物化學(xué)是生物學(xué)和醫(yī)學(xué)研究的必備基礎(chǔ) 12 Definition of Biochemistry Biochemistry is the chemistry of life. The study of the molecular basis of life and the interact with each other or understanding life phenomena in chemical te

8、rms. The combination of biology and chemistry or the application of chemical principles to understand biology. 13 Living organisms vs. inanimate objects chemical complexity and organization use energy in a systemic way self-replication and self-assembly Biochemistry Explains: Diverse lives in unifyi

9、ng chemical terms All macromolecules are made of a few simple compounds 14 Main Questions for Biochemistry I (This semester） What are the composition and structure of bio-molecules? How do these bio-molecules act and interact in living organisms？ 15 1. Protein Structure and Function （蛋白質(zhì)的結(jié)構(gòu)和功能）（蛋白質(zhì)的

10、結(jié)構(gòu)和功能） 2. Enzymes: Basic Concepts and Kinetics (酶的基本概念及酶促動(dòng)力學(xué)酶的基本概念及酶促動(dòng)力學(xué)) 3. Enzymes: Catalytic 6-28%; 為何臨床療效欠佳為何臨床療效欠佳 ? ? 23 Stage I 1870s1930s - Chemical Constitution of Living Organisms Stage II 1930s1950s - Law of Chemical Change and Control of Different Bio-molecules Stage III 1950s present -

11、Principles that are Central for Understanding Living Organisms. The Development of Biochemistry 24 1810 30: C, H, O, and N are the major substances from animals and plants. The term “Protein” was first used in 1838. 1850 90: Carbohydrates, lipids, and nucleic acids were recognized. The term “biochem

12、istry” was formed in 1877 by Hoppe-Seyler. 1890s: Yeast extract ferment sugar to alcohol! Enzymes can function in cell-free system. The era of enzymology developed (1894). 25 1920s James Sumner: Enzymes are proteins. 1940s - 1950s Avery and Hershey: DNA carries the genetic information. 1950s Frankli

13、n, and Watson and Crick: DNA is a double helix. 1960s Nirenberg: Genetic codes deciphered. 1980s Cech: RNA has catalytic activity (Ribosome). 26 近近2020年年 諾貝爾生理和醫(yī)學(xué)獎(jiǎng)中諾貝爾生理和醫(yī)學(xué)獎(jiǎng)中 8080的發(fā)現(xiàn)與生化相關(guān)的發(fā)現(xiàn)與生化相關(guān) 27 Krebs: Citric Acid Cycle (TCA): an important way by which the complex chemical processes provide livi

14、ng organisms with high energy phosphate. Sanger: Sequencing Method Amino acid sequencing method and the complete sequence of insulin. Sanger Sequencing Method for DNA 28 (有莢膜有莢膜, S; 致病性）致病性） 29 30 S (heat-killed) Mouse lives 31 R + S (heat-killed/ extracts) Mouse dies 32 結(jié)果小結(jié)和分析結(jié)果小結(jié)和分析 （背景：以往認(rèn)為（背景：以

15、往認(rèn)為蛋白質(zhì)蛋白質(zhì)攜帶遺傳信息）攜帶遺傳信息） 33 34 Part I Foundations of Biochemistry 1. The molecular logic of life 2. Bio-molecules 3. Cells 4. Water Some Important Chemical Concepts and Principles for Studying Biochemistry 35 General Features of Living Organism complicated and double or triple bonds between two C ato

16、ms. l Covalently linked C atoms can form different structures （linear, branched, or cyclic） ladding functional groups conferring specific activities to the molecules. 42 Versatility of carbon in forming covalent bonds 43 l Organic compounds: Molecules containing covalently bonding carbon backbones;

17、e.g. alcohols, amines, aldehydes (醛醛), ketones, 羧基羧基, 巰基巰基, etc Most bio-molecules are organic compounds. l “C” : tetrahedral arrangement of its four single bonds. C - C single bonds have freedom of rotation, but not double nor triple bonds. l No other chemical element has the capacity to form molec

18、ules of such widely different sizes, shapes, with variety of functional groups 44 45 Most biomolecules can be considered to be derived from hydrocarbons hydrophilic interactions between biomolecules Hydrocarbons 甲烷甲烷己烷己烷 46 fisherBall-and-stickSpace filling Bio-molecules have 3-D structures 47 Bio-m

19、olecules have 3-D structures The special feature of organic compounds is NOT their compositions but the way their atoms are combined (structures, 1820s) Corollary（推論）（推論）: two substances may show the same chemical formula but physically and chemically different materials (different structures and fu

20、nctions). 48 Convention used for configuration 49 Light absorbing pigment in rhodopsin an integral membrane protein 50 Chiral：手性：手性 51 Interactions between bio-molecules are stereo-specific Between pairs of enantiomers 對(duì)映對(duì)映(結(jié)構(gòu)結(jié)構(gòu))體：體： usually only one form is biologically active. L-amino acids (S) ar

21、e found in proteins D-glucose (R) is biologically active Only one chiral form is generated in living cells due to enzyme specificity (1975 Nobel Prize) In vitro chemical synthesis：the two enantiomers are usually synthesized in equal amounts 52 Chewing gums 綠薄荷綠薄荷 香菜香菜 Two stereoisomers may have tota

22、lly opposite biological effects (e.g., Chewing gums) 53 Neutral sweet 天冬酰苯丙氨酸甲酯天冬酰苯丙氨酸甲酯 Aspartame, a sugar substitute; its stereoisomer, bitter 54 Four families: Amino acids；Sugar； Fatty acids；Nucleotides Functions: Used to synthesize larger molecules； Have special biological functions； Involved in

23、 complex reaction pathways； Major Classes of Small Bio-molecules 55 Five general types of reactions in cells: Oxidation-reduction (氧化還原反應(yīng)氧化還原反應(yīng)) Internal re-arrangements (isomerization, 異構(gòu)異構(gòu)) Cleavage Synthesis (increasing order, thus energy consuming) to provide building materials, anabolism 合成代謝合成

24、代謝. 61 Extract energy and reducing power from the environment (生命體通過光合作用和氧化生命體通過光合作用和氧化 作用從外界吸收能并釋放廢棄物）作用從外界吸收能并釋放廢棄物） Generation (interconversion) of all the biomolecules for a living organism (biosynthesis).（伴隨著物質(zhì)和能量代謝，生物伴隨著物質(zhì)和能量代謝，生物 分子間通過分解和合成作用發(fā)生互換分子間通過分解和合成作用發(fā)生互換） 62 Anabolism 合成代謝合成代謝 Catabol

25、ism 分解代謝分解代謝 能源物質(zhì)能源物質(zhì) 中間代中間代 謝產(chǎn)物謝產(chǎn)物 廢棄物廢棄物 63 linear, branched or circular pathways; Highly interconnected 各個(gè)途徑相互交接，形成物與能的網(wǎng)絡(luò)化交流各個(gè)途徑相互交接，形成物與能的網(wǎng)絡(luò)化交流 Tightly regulated to achieve best economy 精密調(diào)控，保證機(jī)體最經(jīng)濟(jì)的利用物質(zhì)和能量精密調(diào)控，保證機(jī)體最經(jīng)濟(jì)的利用物質(zhì)和能量 64 All living organisms are made up of cells, the smallest unit both the structural and functional of living matters. Cells are capable of self-reproduction. Most cells are microscopic in size Eukaryotic cells: 5 - 100 m mm in size； bacteria: 1-2 m mm; mycoplasma: 0.3 m mm Cell: Fundamental Unit of Life 65 Prokaryotic (原核）原核）cells: Lack a nucleus e.g., Eubacteri