1.绪论 氨基酸-20130828

1、Welcome back!,生 物 化 学,Biochemistry,云南大学生命科学学院专业必修课,罗开珺 研究员 硕士生导师 kaijun_ 2013.08.29,一、本学期的课程安排,二、教与学,基本问题（Essential Questions）： 关键问题 （Key Questions）： 章节总结 （Chapter Summarise）： 思考题 （Problems）：自学,1）杨志敏，蒋立科. 生物化学（第2版）. 北京：高等教育出版社，2010. 2）王希成. 生物化学 （第3版）. 北京：清华大学出版社，2010. 3）Lehninger A.L., Nelson D.L. G

2、ermanyDied september 23, 1882, Gttingen; Germany,Friedrich Whler (31 July 1800 23 September 1882) was a German chemist, best known for his synthesis of urea, but also the first to isolate several chemical elements.,（二）“燃烧”学说使“活力论”再次遭遇重创,Justus von Liebig,Justus von Liebig (12 May 1803 18 April 1873)

3、 was a German chemist who made major contributions to agricultural and biological chemistry, and worked on the organization of organic chemistry. As a professor, he devised the modern laboratory-oriented teaching method, and for such innovations, he is regarded as one of the greatest chemistry teach

4、ers of all time. He is known as the father of the fertilizer industry for his discovery of nitrogen as an essential plant nutrient, and his formulation of the Law of the Minimum which described the effect of individual nutrients on crops. He also developed a manufacturing process for beef extracts,

5、and founded a company, Liebig Extract of Meat Company, that later trademarked the Oxo brand beef bouillon cube.,（三）、细胞是生命体的基本结构单位,（四）血红蛋白赋予血液红色,Felix Hoppe-Seyler,Ernst Felix Immanuel Hoppe-Seyler (December 26, 1825 August 10, 1895) was a German physiologist and chemist,（五）酶的化学本质是蛋白质,James Batchelle

6、r Sumner (November 19, 1887 August 12, 1955) was an American chemist. He shared the Nobel Prize in Chemistry in 1946 with John Howard Northrop and Wendell Meredith Stanley.,James B. Sumner,（六）酶是化学反应的主宰,Louis Pasteur,December 27, 1822 September 28, 1895) was a French chemist and microbiologist born i

7、n Dole. He is remembered for his remarkable breakthroughs in the causes and preventions of diseases. His discoveries reduced mortality from puerperal fever, and he created the first vaccine for rabies and anthrax. His experiments supported the germ theory of disease. He was best known to the general

8、 public for inventing a method to stop milk and wine from causing sickness, a process that came to be called pasteurization. He is regarded as one of the three main founders of microbiology, together with Ferdinand Cohn and Robert Koch. Pasteur also made many discoveries in the field of chemistry, m

9、ost notably the molecular basis for the asymmetry of certain crystals.2 His body lies beneath the Institute Pasteur in Paris in a spectacular vault covered in depictions of his accomplishments in Byzantine mosaics.,2、20世纪上半叶是动态生物化学阶段,（一）糖酵解,Gustav Georg Embden (November 10, 1874 - July 25, 1933) was

10、 a German chemist who conducted studies on carbohydrate metabolism and muscle contraction, and was the first to discover and link together all the steps involved in the conversion of glycogen to lactic acid. In 1918 Otto Fritz Meyerhof explained - together with the Jew-Polish-Sovietic biochemist Jak

11、ub Karol Parnas - cellular metabolism by showing that it involved the breakdown of glucose to lactic acid. Embden worked out the precise steps involved in the breakdown. This cellular metabolic sequence from glycogen to lactic acid became known as the Embden-Meyerhof-Parnas pathway. He had also prev

12、iously studied the livers metabolic processes, laying a foundation for understanding diabetes,（二）三羧酸循环是物质氧化分解的最终途径,Hans Adolf Krebs,25 August 1900 22 November 1981,earned him a Nobel Prize in 1953,（三）物质代谢与能量代谢偶联,Albert Lester Lehninger (February 17, 1917 March 4, 1986)2 was an American biochemist in

13、 the field of bioenergetics. He made fundamental contributions to the current understanding of metabolism at a molecular level. In 1948, he discovered, with Eugene P. Kennedy, that mitochondria are the site of oxidative phosphorylation in eukaryotes, which ushered in the modern study of energy trans

14、duction. He is the author of a number of classic texts, including: Biochemistry, The Mitochondrion, Bioenergetics and, most notably, his series Principles of Biochemistry. The latter is a widely used text for introductory biochemistry courses at the college and university levels.,LEHNINGER PRINCIPLE

15、S OF BIOCHEMISTRY Fifth Edition,(四) 合成代谢和分解代谢组成“中间代谢”网络,3、20世纪50年代生物化学发展进入到分子生物学时期,（一）a 螺旋是蛋白质分子二级结构形式之一,Linus Pauling,Linus Carl Pauling (February 28, 1901 August 19, 1994)1 was an American chemist, biochemist, peace activist, author and educator.,Frederick Sanger,Frederick Sanger, OM, CH, CBE, FRS

16、 (born 13 August 1918) is an English biochemist and a two-time Nobel laureate in chemistry, the only person to have been so.,（二）DNA是遗传的物质基础,Friedrich Miescher,Johannes Friedrich Miescher (13 August 1844, Basel 26 August 1895, Davos) was a Swiss physician and biologist. He was the first researcher to

17、 isolate and identify nucleic acid.,George Wells Beadle,one gene, one enzyme”,Edward Lawrie Tatum,(December 14, 1909 November 5, 1975) was an American geneticist.,(October 22, 1903 June 9, 1989) was an American scientist in the field of genetics, and Nobel Prize in Physiology or Medicine Nobel laure

18、ate who with Edward Lawrie Tatum discovered the role of genes in regulating biochemical events within cells.,（三）DNA双螺旋是揭示遗传信息传递的“敲门砖”,James D. Watson,James Dewey Watson (born April 6, 1928) is an American molecular biologist, geneticist, and zoologist, best known as one of the co-discoverers of the

19、structure of DNA in 1953 with Francis Crick.,Francis CrickDiscovery of the DNA Double Helix,Francis Harry Compton Crick OM FRS (8 June 1916 28 July 2004) was an English molecular biologist, biophysicist, and neuroscientist, and most noted for being one of two co-discoverers of the structure of the D

20、NA molecule in 1953, together with James D. Watson.,DNA DNA RNA Proteins Proteins Metabolic products,（四）遗传信息按中心法则传递,（五）基因信息传递是被特殊机制调节的,（六）DNA“克隆”使基因操作无所不能,三、当代生物化学研究的内容,1、生物分子的结构和功能,2、物质、能量代谢及其调节,3、遗传信息传递及其调控,第一章,氨基酸 Amino Acids,一、组成人体的20种氨基酸均属于L-a-氨基酸,二、20种氨基酸的侧链结构及极性迥然不同,三、20种氨基酸具有共同或特异的理化性质,四、-氨基

21、参与多种化学反应,五、氨基酸的-氨基与-羧基共同参与茚三酮反应,六、一个氨基酸的羧基可与另一个氨基酸的氨基反应成肽,19世纪末，Emil Fischer证明蛋白质是由氨基酸组成的，并用氨基酸合成了多种短肽 。,课前5分钟,“臭烘烘的化学家埃米尔费雪”,“最年轻的博士”,由于他的辛勤劳动，人们认识了19种氨基酸，自然界中有几十万种蛋白质，而它们都是由20种氨基酸以不同数量比例和不同排列方式结合而成的。,University Palace, main building of the former Imperial University of Strasbourg,课前5分钟,存在自然界中的氨基酸有

22、300余种，但组成人体蛋白质的氨基酸仅有20种，且均属 L-氨基酸（甘氨酸除外）。,一、组成人体的20种氨基酸均属于L-氨基酸,按Fischer投影式：羧基在上方，氨基在左侧的是L型，在右侧的是D型。 费歇尔以甘油醛为标准，以D/L命名与甘油醛联系的旋光性的化合物。D、L命名法区分的构型与旋光性没有必然关系。 天然氨基酸（构成蛋白质的）都是L型。,L-氨基酸的通式 （R为侧链）,L-氨基酸,-氨基酸,氨基酸分类,疏水性氨基酸 极性氨基酸,中性氨基酸 酸性氨基酸 碱性氨基酸,脂肪族氨基酸 芳香族氨基酸,(一)侧链含烃链的氨基酸属于非极性脂肪族氨基酸,二、20种氨基酸的侧链结构及极性迥然不同,此类

23、氨基酸有甘氨酸、丙氨酸、缬氨酸、亮氨酸、异亮氨酸、甲硫氨酸和脯氨酸。 此类氨基酸在水溶液中溶解度小。,甘氨酸 glycine Gly G 5.97,丙氨酸 alanine Ala A 6.00,缬氨酸 valine Val V 5.96,亮氨酸 leucine Leu L 5.98,异亮氨酸 isoleucine Ile I 6.02,苯丙氨酸 phenylalanine Phe F 5.48,脯氨酸 proline Pro P 6.30,非极性疏水性氨基酸,中性氨基酸有丝氨酸、半胱氨酸、苏氨酸、天冬酰胺和谷氨酰胺。,（二）侧链有极性但不带电荷的氨基酸是极性中性氨基酸,极性中性氨基酸,(三)侧

24、链含芳香基团的氨基酸是芳香族氨基酸,此类氨基酸有苯丙氨酸、酪氨酸和色氨酸，其侧链分别有苯基、酚基和吲哚基。,芳香族氨基酸,(四)侧链含负性解离基团的氨基酸是酸性氨基酸,此类氨基酸有天冬氨酸、谷氨酸，其侧链都含有羧基，均可解离而带负电荷。,酸性氨基酸,(五)侧链含正性解离基团的氨基酸属于碱性氨基酸,此类氨基酸有赖氨酸、精氨酸和组氨酸，其侧链分别含有氨基、胍基和咪唑基，均可发生质子化，使之带正电荷。,碱性氨基酸,（六）几种特殊氨基酸,脯氨酸 （亚氨基酸）, 半胱氨酸,胱氨酸,修饰性氨基酸,羟赖氨酸HO-Lys 羟脯氨酸HO-Pro 苏氨酸、丝氨酸、酪氨酸磷酸化 丝氨酸糖基化 天冬酰胺糖基化,三、2

25、0种氨基酸具有共同或特异的理化性质,（一）氨基酸具有两性解离性质,氨基酸是两性电解质，其解离程度取决于所处溶液的酸碱度。,从上图可知：氨基酸在酸性环境中，主要以阳离子的形式存在，在碱性环境中，主要以阴离子的形式存在。在某一pH环境下，以两性离子（兼性离子）的形式存在。该pH称为该氨基酸的等电点。所以氨基酸的等电点可以定义为：氨基酸所带正负电荷相等时的溶液pH。,pH=pI,pHpI,pHpI,氨基酸的兼性离子,阳离子,阴离子,等电点 (isoelectric point, pI),在某一pH的溶液中，氨基酸解离成阳离子和阴离子的趋势及程度相等，成为兼性离子，呈电中性。此时溶液的pH值称为该氨基酸的等电点。,理论意义： 生物分子的活性状态与分子的带电状态有关，而带电状态有pI和环境pH有关。 实践意义： 电泳、离子交换层析、沉淀法等分离分析方法的基础。,（二） 氨基酸具有特征性的滴定曲线,甘氨酸滴定曲线,从氨基酸的酸碱滴定曲线可以进一步讨论羧基和氨基解离和等电点的关系,（三）含共轭双键的氨基酸具有紫外吸收性质,芳香族氨基酸的紫外吸收峰在 280nm 附近。,大多数蛋白质含有芳香族氨基酸残基，所以测定蛋白质溶液280nm的光吸收值是分析溶液中蛋白质含量的快速简便的方法。,（四） -氨基、羧基分别参与多种化学反应,Schiff碱,醛,氨基酸