Why do ants like fingernail sections

Wöhler's Discovery - Another Introduction to Biochemistry [1. Ed.] 978-3-662-58858-1; 978-3-662-58859-8

Table of contents:
Front Matter .... Pages I-X
First excursion: A journey back in time (Dieter Neubauer) .... Pages 1-34
Second excursion: To the arduous life in the primeval soup (Dieter Neubauer) .... Pages 35-76
Third excursion: Into the green (Dieter Neubauer) .... Pages 77-110
Fourth excursion: To encrypted messages (Dieter Neubauer) .... Pages 111-135
Fifth excursion: To a wonderland (Dieter Neubauer) .... Pages 137-161
Sixth excursion: Through thick and thin (Dieter Neubauer) .... Pages 163-190
Seventh excursion: Into the realm of vitamins and hormones (Dieter Neubauer) .... Pages 191-217
Back Matter .... Pages 219-232

Citation preview

Dieter Neubauer

Wöhler's Discovery - Another Introduction to Biochemistry

Wöhler's Discovery - Another Introduction to Biochemistry

Dieter Neubauer

Wöhler's Discovery - Another Introduction to Biochemistry

Dieter Neubauer Wachenheim an der Weinstrasse Germany

ISBN 978-3-662-58858-1 ISBN 978-3-662-58859-8 (eBook) https://doi.org/10.1007/978-3-662-58859-8 The German National Library lists this publication in the German National Bibliography; detailed bibliographic data are available on the Internet at http://dnb.d-nb.de. Springer Spectrum © Springer-Verlag GmbH Germany, a part of Springer Nature 2019 The work including all its parts is protected by copyright. Any use that is not expressly permitted by copyright law requires the prior consent of the publisher. This applies in particular to copying, editing, translation, microfilming and saving and processing in electronic systems. The reproduction of generally descriptive designations, brands, company names etc. in this work does not mean that they can be freely used by anyone. The authorization for use is subject to the rules of trademark law, even without separate notice. The rights of the respective owner of the mark are to be observed. The publisher, the authors and the editors assume that the details and information in this work are complete and correct at the time of publication. Neither the publisher, nor the authors or editors, expressly or implicitly, guarantee the content of the work, any errors or statements. The publisher remains neutral with regard to geographical assignments and territorial designations in published maps and institutional addresses. Planning: Sarah Koch Drawings: Wolfgang Zettlmeier, Barbing Springer Spectrum is an imprint of the registered company Springer-Verlag GmbH, DE and is part of Springer Nature. The address of the company is: Heidelberger Platz 3, 14197 Berlin, Germany

Preface

The world of modern science is ruled by the vast empires of physics, biology, medicine and chemistry. Enclosed between them and adjacent to all four is an area that was only discovered by Friedrich Wöhler almost 200 years ago and then quickly explored by numerous even more famous researchers: biochemistry. In contrast to its larger neighbors, it has the attraction of being close to nature and remaining peaceful. Neither explosion hazard nor smell, non-corrosive, without environmental damage, no eternally radiating waste, also no deadly weapons, instead mild conditions, gentle procedures, medicines and test strips, new crops, enzymes, vitamins and hormones - in short: a promising, gentle natural science. Which also arouses awe at the miracle of life and turns out to be absolutely indispensable for understanding our world. Many therefore want to get to know them better (and some even have to). Hopefully they set out to hike their rugged terrain. But impassable paths and difficult-to-understand signposts make the advance difficult. This introduction is dedicated to those who do not want to give up but hope for help. It is different from the others, but perhaps because of that it is useful. I am confident: with it, the curious hiker will ultimately enjoy the delightful views back and forth that await him on the way and that previously seemed so inaccessible to him. Dieter Neubauer

V.

Table of Contents

1 First excursion: a journey back in time. . . . . . . . . . . . . . 1 1.1 A little tool for understanding. . . . . . . . . . . . . . . . . . . . 5 1.2 Good news from biochemistry. . . . . . . . . . . . . . . . . . . . . . 6 1.3 The Significance of Stanley Miller's Experiments. . . . . . . . . . . . . . 8 1.4 From amino acids to protein. . . . . . . . . . . . . . . . . . . . . . . . 9 1.5 From the origin of life. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 1.6 Asymmetric Molecules and Optical Isomers. . . . . . . . . . . . . . 12 1.7 Where were the D-amino acids ?. . . . . . . . . . . . . . . . . . . . . . . . . . 13 1.8 Fiber proteins: wool and silk. . . . . . . . . . . . . . . . . . . . . . . . . . . 13 1.9 Reading off macroscopic properties from structural formulas. . . . 17 1.10 Man-made fibers that are also polyamides. . . . . . . . . . . . . . . . . . . . 18 1.11 The versatile role of the side chains. . . . . . . . . . . . . . . . . . . . . . 20 1.12 How to describe a polypeptide. . . . . . . . . . . . . . . . . . 21 1.13 Handicapped maneuverability. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23 1.14 An attempt at analogy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23 1.15 The role of hydrogen bonds. . . . . . . . . . . . . . . . . . . . . . . . . 24 1.16 A detour to bakeries and kitchens. . . . . . . . . . . . . . . . . . . 26 1.17 hair. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 1.18 From skin, horn and hoof to globular polypeptides. . . . . . 29 1.19 Protein compounds in our food. . . . . . . . . . . . . . . . . . . 30 1.20 What becomes of the protein in our body. . . . . . . . . . . . . . . . . . 31 1.21 Wöhler's discovery. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32 1.22 Another farewell look into the world of proteins. . . . . . . . . . . . . 33 2 Second excursion: To the arduous life in the primordial soup. . . . . . . . . . 35 2.1 Living only on energy - is that possible? . . . . . . . . . . . . . . . . . . . . . . . . 36 2.2 How bacteria digest glucose. . . . . . . . . . . . . . . . . . . . 36 2.3 Continuation of glycolysis: the production of sauerkraut. . . . . . . . . 47 2.4 Chase and sore muscles. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49 2.5 This way to the crime scene. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50 2.6 The citric acid cycle. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52 2.7 Repetition is the mother of learning. . . . . . . . . . . . . . . . 56 2.8 A kind of balance sheet. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59 2.9 The citric acid cycle and other degradation reactions. . . . . . . . . 60 VII

Table of Contents

VIII

2.10 2.11 2.12 2.13 2.14 2.15 2.16 2.17 2.18 2.19 2.20 2.21 2.22

Finally: the respiratory chain. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61 An amazing comparison. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62 The complex I (NADH-Q oxidoreductase). . . . . . . . . . . . . . . . . 63 A proton pump. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64 The complex IV: the cytochrome oxidase. . . . . . . . . . . . . . . . . . 67 The complex II: succinate Q reductase. . . . . . . . . . . . . . . . . . . . 68 How adenosine triphosphate is made. . . . . . . . . . . . . . . . . . . . . . . . . 69 A turbine runner of molecular size. . . . . . . . . . . . . . . . . . 70 Why the turbine wheel turns. . . . . . . . . . . . . . . . . . . . . . . . 72 The scene of glycolysis and the Krebs cycle. . . . . . . . . . . 73 A shuttle service for NADH. . . . . . . . . . . . . . . . . . . . . . . . . . . . 74 How the respiratory chain is regulated. . . . . . . . . . . . . . . . . . . . . . . 75 A look back. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76

3 Third excursion: into the countryside. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77 3.1 The ingenious invention of blue-green algae. . . . . . . . . . . . . . . . . . . . . . . 77 3.2 Where does the oxygen come from ?. . . . . . . . . . . . . . . . . . . . . . . . . . . . 78 3.3 A food made from metabolic waste products. . . . . . . . . . . . . . 80 3.4 Photosynthesis in eukaryotes. . . . . . . . . . . . . . . . . . . . . . . . 80 3.5 The carbon dioxide is converted. . . . . . . . . . . . . . . . . . . . . . . . . 84 3.6 The dark reaction of photosynthesis. . . . . . . . . . . . . . . . . . . . . 86 3.7 A feedback from the distant past. . . . . . . . . . . . . . . . . . . . . 86 3.8 A synthesis that feeds the world…. . . . . . . . . . . . . . . . . . . . . . 86 3.9 ... and changed the world. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87 3.10 The simple photosynthesis of the sulfur bacteria. . . . . . . . . . . 88 3.11 The reaction product, glucose. . . . . . . . . . . . . . . . . . . . . . 88 3.12 All foods are made from glucose. . . . . . . . . . . . 92 3.13 The small difference. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96 3.14 Two different grape sugar molecules. . . . . . . . . . . . . . . . . 97 3.15 Optically Active Molecules. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98 3.16 Pasteur sorts optically active salt crystals. . . . . . . . . . . . . . . . . . 101 3.17 Van’t Hoff determines the direction of the tie arms. . . . . . . . . . . . 102 3.18 Food or building material? . . . . . . . . . . . . . . . . . . . . . . . . 105 3.19 Cane sugar has been around for almost 2000 years. . . . . . . . . . . . . . . . . . . . 105 3.20 Biochemical sugar cleavage in nature. . . . . . . . . . . . . . . . . . 107 3.21 From the glucosides to the glycosides. . . . . . . . . . . . . . . . . . . . 108 3.22 At the destination. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 109 4 Fourth excursion: To encrypted messages. . . . . . . . . . . . . . . . . 111 4.1 Puzzles on Puzzles. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111 4.2 What can be seen under the microscope. . . . . . . . . . . . . . . . . . . . . . 112 4.3 DNA - an old friend. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114 4.4 A researcher's race to elucidate structures. . . . . . . . . . . . . . . . 116 4.5 A molecule with a double helix. . . . . . . . . . . . . . . . . . . . . . . . . . . 116 4.6 The decoding of the human genome. . . . . . . . . . . . . . 117

Table of Contents

4.7 4.8 4.9 4.10 4.11 4.12 4.13 4.14 4.15 4.16 4.17 4.18 4.19

IX

A four-letter cipher. . . . . . . . . . . . . . . . . . . . 120 An alternative description of DNA. . . . . . . . . . . . . . . . . . . . 120 The replication - or multiplication. . . . . . . . . . . . . . . . . . . . . . . 123 The DNA polymerase is not infallible…. . . . . . . . . . . . . . . . . 124 ... but it corrects itself.. . . . . . . . . . . . . . . . . . . . . . . . . . 125 A famous attempt. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126 From replication to transcription. . . . . . . . . . . . . . . . . . . . . . 126 A new player: RNA. . . . . . . . . . . . . . . . . . . . . . . . . . . 127 Sledding Enzyme Complexes. . . . . . . . . . . . . . . . . . . . . . . . 129 And now: the translation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 130 A detour into mathematics. . . . . . . . . . . . . . . . . . . . . . . . . . 133 Data security for genetic information. . . . . . . . . . . . . . . . . . . . . 134 Now it's time to rest. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135

5 Fifth excursion: to a wonderland. . . . . . . . . . . . . . . . . . . . . . . . . . . 137 5.1 Enzymes work precisely. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 138 5.2 It all depends on the correct pH value. . . . . . . . . . . . . . . . . . . . 139 5.3 A look into the workshop. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141 5.4 The Enzyme as a Force of Order. . . . . . . . . . . . . . . . . . . . . . . . . . . . 142 5.5 Enzymes link reactions with one another. . . . . . . . . . . . . . . . 144 5.6 Enzymes have a specific effect. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 148 5.7 Enzymes with inhibitions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 150 5.8 We meet old friends. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151 5.9 Now it's getting boring: The names. . . . . . . . . . . . . . . . . . . . . . . . 152 5.10 Limits of effectiveness. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 154 5.11 Cars without accelerator and brakes ?. . . . . . . . . . . . . . . . . . . . . . . 155 5.12 Indispensable helpers: the cofactors. . . . . . . . . . . . . . . . . . . . . 159 5.13 The class society of enzymes. . . . . . . . . . . . . . . . . . . . . . . 160 5.14 A Disappointing End ?. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 161 6 Sixth excursion: through thick and thin. . . . . . . . . . . . . . . . . . . . . . . . 163 6.1 Sugar doesn't make you fat! Or is it? . . . . . . . . . . . . . . . . . . . . . 163 6.2 A way from glucose to palmitic acid? . . . . . . . . . . . . . 164 6.3 There is a way - we go about it. . . . . . . . . . . . . . . . . . 165 6.4… and on to unsaturated fatty acids…. . . . . . . . . . . . . . 169 6.5 Fats are esters of fatty acids with glycerine. . . . . . . . . . . . . . . . . 170 6.6 A word about fat digestion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 171 6.7 Soap molecules at work. . . . . . . . . . . . . . . . . . . . . . . . . . . . 173 6.8 How fat is broken down. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 178 6.9 A detour to other lipids. . . . . . . . . . . . . . . . . . . . . . . . . 183 6.10 Phosphoglycerides. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 184 6.11 Membrane, now finally. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 186 6.12 Equally good with fat and water Freund: the emulsifier. . . . . . . . . 188 6.13 At the end of our sixth excursion. . . . . . . . . . . . . . . . . . . . . . . 189

X

Table of Contents

7 Seventh excursion: Into the realm of vitamins and hormones. . . . . . . 191 7.1 With Magellan across the Pacific. . . . . . . . . . . . . . . . . . . . . . . . . . . . 191 7.2 Vitamin C - a miracle cure ?. . . . . . . . . . . . . . . . . . . . . . . . . . . 193 7.3 Chemistry of Vision. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 195 7.4 A stroke of the oar in molecular dimensions. . . . . . . . . . . . . . . 196 7.5 Vitamin A and Carotene. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 197 7.6 A puzzling disease in East Asia. . . . . . . . . . . . . . . . . . . . . . 198 7.7 A human experiment sheds light on the darkness. . . . . . . . . . . . . 199 7.8 The vitamin B1. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 199 7.9 Flavin and other acquaintances. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 200 7.10 A few puzzling processes. . . . . . . . . . . . . . . . . . . . . . . . . . . . 203 7.11 A versatile plant hormone. . . . . . . . . . . . . . . . . . . . . . . . . . 203 7.12 Ethylene as a postman. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 204 7.13 On to the Langerhans Islands. . . . . . . . . . . . . . . . . . . . . 205 7.14 The history of diabetes. . . . . . . . . . . . . . . . . . . . . . . 205 7.15 Insulin synthesis by cleavage reactions. . . . . . . . . . . . . . . . . . 207 7.16 The distribution. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 209 7.17 How the β-cell measures sugar concentrations. . . . . . . . . . . . . . . . 210 7.18 What insulin does with blood sugar. . . . . . . . . . . . . . . . . . 210 7.19 Reversal of the direction of march through Glucagon. . . . . . . . . . . . . . . . 211 7.20 Other Effects of Insulin. . . . . . . . . . . . . . . . . . . . . . . . . . . 211 7.21 The adrenaline. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 211 7.22 A tiny grain of adrenaline is enough…. . . . . . . . . . . . . . . . . 213 7.23 ... because an avalanche has started. . . . . . . . . . . . . . . . . . . . . . . . . . . . 213 7.24 Synthesis and Biosynthesis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 215 7.25 A view from the summit. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 216 Safari: to an idiosyncratic element. . . . . . . . . . . . . . . . . . . . . . . . . . . 219 Subject and person index. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 223

1

First excursion: a journey back in time

Let's turn back our clocks! Not to Adam and Eve, but considerably further, but also not to the creation or emergence of our world. Four billion years should be enough for us to pause and take a curious look at our surroundings. It looks a lot different than it does today. Everywhere volcanoes tirelessly spew glowing fountains of lava into the atmosphere. Lava flows roll over a barely solidified surface of the earth. Wherever they plunge into the warm or hot sea, huge clouds of water vapor arise with hissing and hissing. These rise, cool down, charge themselves electrically and go down incessantly as torrential thunderstorms. Flashes of lightning constantly illuminate the night - or the day, which is hardly different from the night under the dense cloud towers. No trace of animals or plants. Not from any life. No wonder, since the atmosphere does not consist of nitrogen and oxygen, but of water vapor, ammonia, methane, hydrogen and nitrogen, lots of asphyxiating or poisonous gases. How could life arise there? A Russian chemist named Alexander Ivanovich Oparin1 attempted to solve this question almost a hundred years ago. Since he published his theory in Russian in a largely unknown monograph, he has to share the fame today with the Englishman J.B.S Haldane2, who in 1929 made similar considerations independently of him. The two assumed that due to solar radiation and lightning discharges in a reducing - i.e. oxygen-free - primordial atmosphere

1Alexander Ivanovich Oparin lived from 1894–1980, mostly in Moscow.He was a Lenin Prize laureate, a hero of Socialist Labor and a member of the Soviet Academy of Sciences. 2John Burdon Sanderson Haldane was an extremely versatile biologist close to atheism and communism. He lived from 1892 to 1964, mainly in England, but because of government policy during the Suez Crisis, he took Indian citizenship and died in his new home.

© Springer-Verlag GmbH Germany, part of Springer Nature 2019 D. Neubauer, Wöhler's Discovery - Another Introduction to Biochemistry, https://doi.org/10.1007/978-3-662-58859-8_1

1

2

1 First excursion: a journey back in time

Fig. 1.1 The apparatus

Spark gap

cooling water

Heating fluid

burner

Organic molecules arose which were able to grow in this "primordial soup" by adding more molecules and finally - surrounded and protected by a membrane - developed into the first living beings. Two Americans, Harald C. Urey3 and Stanley Lloyd Miller4, checked these considerations from 1953 onwards with the help of an ingeniously devised simple test apparatus. But how can a researcher in the laboratory imitate the environmental conditions of prehistoric times? The apparatus with which Miller, then still a student, carried out his experiments at Urey's suggestion, is shown in Fig. 1.1. It essentially consists of a closed circuit in which water vapor is generated and superheated, which then runs through a spark gap, then liquefies again by cooling and then returns to the boiling flask via overflow. He filled the apparatus with water and a gas mixture of methane, ammonia and hydrogen. The structural formulas of these four starting materials are shown in Fig. 1.2. After an operating time of one week, he was able to detect amino acids in the reaction liquid. Because protein compounds can be formed from amino acids, he created the building blocks of life from purely inorganic raw materials. There are also organic molecules such as hydrocyanic acid, dicyan, cyanoacetylene and aldehydes. You can see the associated formulas in Fig. 1.3.

3Harald Clayton Urey was an American chemist who lived from 1893-1981. 1934 Nobel Prize for the discovery of heavy hydrogen. A moon crater and an asteroid are named after him. 4Stanley Lloyd Miller was born in Oakland, California in 1930 and died in San Diego in 2007.

1 First excursion: a journey back in time

3

Fig. 1.2 The raw materials

H

O

H H

H

Steam

hydrogen

N

C.

H H

H

H

H

Ammonia NH 3

Fig. 1.3 Reaction products

H

H

Methane CH4

H H C N

C O H formaldehyde

Hydrogen cyanide (hydrogen cyanide)

C O

N C C N

Carbon monoxide

Dicyan

N C C CH

H

Cyanoacetylene H H H O H C C C H H H

H

O

N C C H

OH

Aminoacetic acid (glycine)

Propionaldehyde

Miller's attempts have since been checked and modified thousands of times, but never refuted. On the contrary, it was found that life building blocks such as amino acids and their secondary products, the peptides, are also created in a less reducing or even more neutral atmosphere. The fact that longer cycle times are required in this case is no argument against Oparin's and Haldane's claims about the emergence of precursors of life from inorganic substances. And further: By systematically modifying the reaction conditions, adding or leaving out starting materials, using ultraviolet light or heat instead of electrical discharges, it has been possible to generate an enormous number of organic compounds. A very limited selection of these end products is shown in Fig. 1.4 and some examples of the reactions that take place in the “primordial soup” can be found in Fig. 1.5. It will surely make sense to you that many of the reaction products described can in turn react with one another in a variety of ways in the hot liquid or in the vapor space. The modified tests according to Urey-Miller also showed that no “primordial soup” was created when oxygen was present in the vapor space of the circulatory apparatus.

1 First excursion: a journey back in time

4 Fig. 1.4 Even more reaction products

O

O

H HO H H

OH

C.

H C OH CH 3 lactic acid

O

H C C OH C H C OH C OH CH 2 OH

R.

R C O + NH

R 3

H

H

2

R H

C.

OH NH 2

H

R H

C.

NH 2

R.

R.

O

O NH 2 O

H 2N C C

+ HOH NH 2

H

Ph en yla la n in - an amino acid

H 2N C C H

H 2N C C

H

+ HO H

R.

H2N C C N + HOH H

4

O

a urea compound

C N

R.

3

H

NH 2

+ H C N

H

+ NH

3

OH

1 to 4: amino acids from aldehydes and hydrogen cyanide R1

5

H

R2

O

O

+ H 2N C C

H 2N C C OH

H

R1

O R2

H 2N C C OH

H

Formation of a dipeptide from two amino acids

6

5 HCN

?

N

N N

N H

Adenine from hydrogen cyanide

Fig. 1.5 Some reactions

O + HOH

N C C H H

NH 2

Purine

H O H 2N C C HCH OH

OH

C.

N H

N C N

G l yc e r i n a l d e h yd

1

Pyrimidine

H

C H C OH H C OH H

N

N

glucose

N

N

N

OH

1.1 A few tools for understanding

5

1.1 A little tool for understanding You can safely skip the following paragraph if you have already learned inorganic or organic chemistry and have not forgotten it. Then you will remember that there are 118 elements - these are substances that cannot be broken down into components by any chemical or other process, because they consist of only a single kind of atoms. Chemists have got used to assigning a letter or two to each element. For example, sulfur is S, magnesium is Mg, and chlorine is Cl. These letters make it possible to describe connections between the elements in the so-called sum formulas. The formula FeS is assigned to the compound that forms iron (Fe) with sulfur (S). Nowadays everyone knows that water is assigned the formula H2O, which means that one oxygen atom (O) holds two hydrogen atoms (H) in every water molecule. Most compounds have more complicated molecular formulas. Quite well known is that of alcohol, which is more precisely called "ethyl alcohol" or "ethanol", it is C2H5OH. You could actually write C2H6O, that would be easier! Why not do it? Because there are two “isomeric” compounds with this molecular formula. The other is called “Dimethylether” and has the structural formula H3C – O – CH3. In contrast to the ambiguous molecular formula, these two “structural formulas” are unambiguous. That of the dimethyl ether says that the oxygen atom (O) holds two methyl groups (-CH3) and it also reveals that in each methyl group one carbon atom (C) binds three hydrogen atoms (H). You can also see immediately that all six hydrogen atoms in it are equivalent, because they are all bound to one carbon atom. In contrast, the structural formula of ethyl alcohol shows that the oxygen atom here holds an “ethyl group” (-C2H5) and a hydrogen atom. If you write them down in more detail, namely H H3C C OH H

it can be seen that the ethyl group consists of two carbon atoms that are linked to one another via a carbon-carbon bond. One of the two holds three hydrogen atoms, the other only two and the oxygen of the OH group. Of the six hydrogen atoms, one is bound to oxygen, the other five to carbon atoms - so they are not all of the same value. The hydrogen atom bound to oxygen will behave differently towards certain reactants than the other five hydrogen atoms. I am sure you will believe me that even a little more complicated compounds such as butyl alcohol with the molecular formula C4H10O still have a lot

1 First excursion: a journey back in time

6

have more isomers5 and can only be correctly described with the help of the structural formula or (usually much more complicated) with a name of their own. The jumble of isomers for empirical formulas such as C18H36O2 or C12H22O11, to name just two more examples out of an incredible number, becomes even more complicated. Molecular formulas and structural formulas are therefore not inventions by malicious chemists, which serve to torment schoolchildren and students unnecessarily, but indispensable tools for finding your way through the jungle of compounds. You have certainly also noticed that in the structural formulas presented so far, all carbon atoms extend four bond arms, oxygen atoms two and hydrogen atoms one. If you also take a closer look at the structural formula of methane in Fig. 1.2, you can see the spatial arrangement of the four hydrogen atoms around the carbon atom. This is because they occupy the corners of a tetrahedron with the carbon atom at its center. And you will surely breathe a sigh of relief when I assure you that this tetrahedral arrangement of the four binding partners of carbon also occurs in almost all compounds that we will get to know. The spatial structure of the ammonia molecule is very similar, because here, too, we meet the three hydrogen atoms in the corners of a tetrahedron, but a lone pair of electrons occupies the path towards the fourth corner, just as if it were a binding partner. It is not easy to see the tetrahedral structure of the water molecule. But if you accept that only two hydrogen atoms are available for two tetrahedron corners and that two electron pairs point in the direction of the other corners, then you can easily see the same construction plan. The water molecule is therefore built at an angle with a "bond angle", which mathematicians tell us to be 109 °. Because of the underlying tetrahedral structure, the bond angle also has this value for nitrogen and carbon.

1.2 Good news from biochemistry We receive encouraging news just in time before we are finally exhausted. In biochemistry we will not come across all 118 elements by any means, but only a selection of 11 frequently and a further dozen rarely or even very rarely. Of the 23 elements that life needs for its chemistry, seven are non-metals and four metals are fairly common. The first group consists of the elements carbon (C), hydrogen (H), oxygen (O), nitrogen (N), sulfur (S) and phosphorus (P), easy to remember with the made-up word CHONSP.

5Es

there are no less than 7 isomers!

1.2 Good news from biochemistry

7

In addition, there is chlorine, usually as a negatively charged chloride ion. We already know that carbon always has 4 binding arms. Nitrogen has 3 and much less often 5 binding arms, sulfur 2 (exceptionally 4 or 6) and phosphorus usually 5. The four metals in the second group are potassium, sodium, magnesium and calcium. Potassium and sodium each have one, the other two metals each have two binding arms. The remaining 12 elements are trace elements: iron, zinc, copper, manganese, cobalt, molybdenum, iodine, fluorine, selenium, chromium, silicon and nickel. Let's move on to the bond lines, which in the structural formulas indicate a chemical bond between two elements! Here I must not hide from you that with non-metals, each bond line actually consists of two electrons (so-called valence electrons), of which each bond partner has contributed one. In the chemical bond they are located between the two partner atoms and bring about their cohesion in the "homeopolar" or "covalent" bond. So it is very similar to a marriage between two wealthy partners: everyone contributes to the cohesion of the marital bond with their possessions - love, sex, debts and children left aside. The simple definition of the “homeopolar” or “covalent” chemical bond as a pair of electrons in common ownership is, of course, pure doctrine, so to speak, because on closer inspection, it is not always shared honestly. The oxygen atom longs for electrons so much that it likes to pull something towards itself, regardless of whether it actually belongs to a carbon atom or a hydrogen atom. The greedy oxygen atom receives a negative partial charge, the involuntary donor a positive one. The nitrogen atom has a similar preference. Another advantage of our notation: The hyphen reveals that the atoms at both ends can be rotated around an axis like balls or wheels. Fortunately, these simple ideas are sufficient for almost all purposes and quite correct in the imagination of the mostly simple-thinking chemists. When looking at the formulas in our figures, you will surely notice that sometimes with nitrogen or oxygen atoms not only lines are drawn to the neighboring atoms, but also lines attached to the atom, which are obviously not needed in this connection. However, we have already noticed in Fig. 1.2 that such adjacent hyphens always mean a non-bonding pair of electrons. If you see two atoms in a formula that are linked by two lines of bonds, you have a double bond in front of you, which is logically made up of two pairs of electrons. The double line shows again very nicely that there is no free rotation here. A triple bond can also occur, it consists of three electron pairs that the bond partners share. The free rotation is even more impossible here. Important: For convenience, chemists often leave out the letter C in their structural formulas for carbon atoms. One carbon atom stands

8

1 First excursion: a journey back in time

then where a kink is drawn in the structural formula. Sometimes there is nothing visible at all of hydrogen atoms. If necessary, spatial structures are indicated by hyphens that are thickened or thinned in perspective. If you look up chemical compounds in Wikipedia, you will often come across such simplified structural formulas. With a little practice, you can easily learn to interpret them correctly. We will also make use of them in formulas and illustrations. For the conversion of such structural formulas into the classical notation, it is always helpful to assume a carbon atom where connecting lines meet at an angle. You have to write hydrogen atoms where the carbon atom appears to have fewer than four bonds. Understanding the bonding arms of metals is not much more difficult. Fortunately, we will only meet them when we are already fairly confident in the broad field of biochemistry. Let me just say that they do not have the binding electrons in common ownership. It is rather the case that the metal atom does not want to keep its binding electrons at all and, if possible, imposes it on a non-metal - just as if it were debt. Because, as you may recall, each electron carries a negative electrical elementary charge, this transfer of electrons makes the metal atom positively and the non-metal atom negatively charged. (To stick with the comparison: the debt hump becomes richer and the wealthy partner poorer - a fair balance, so to speak). The "heteropolar" or "ionic bond" between the two is created because positive and negative attract each other. Often the bond is not written with a hyphen, but the electrically charged atoms or groups of atoms - also called ions - are identified by the signs + or -. To continue with the comparison: marriages between debtors and financiers can also stick together. And in the business world there is usually a stable, friendly, if not exactly loving relationship between debtor and creditor. But now back to the chemistry and the ingredients of the primeval soup! Wherever we find puzzling things there, we want to make them understandable by means of footnotes.

1.3 The Significance of Stanley Miller's Experiments Most people are not clear about the significance of Stanley Miller's experimental results. You, dear reader, are among the minority who will draw correct conclusions from you if you consider the following: There is as yet no evidence that our natural laws could be invalid anywhere in space. The chemical reactions that we can observe or carry out on our planet are also possible on other planets with Earth-like properties. This means that everywhere in space where there are earth-like planets, precursors of life must arise! And that emerges from these precursors if they were long enough

1.4 From amino acids to protein

9

how life inevitably developed on our earth.Maybe even intelligent life! With the enormous number of sun-like fixed stars in space - there are said to be around 1,020, i.e. a hundred billion billion6 of them, every fifth has an Earth-like planet according to the measurements of the Kepler space telescope - it is almost certain that at least one of these 20 billion intelligent life occurs in the terrestrial solar satellites. In the meantime, there are actually increasing indications of life in space. With the help of the Rosetta space probe, it has been possible to detect the amino acid glycine on Comet Tschuri. Even before that, amino acids were found in meteorites. They obviously survive the journey in space and the hard landing on earth undamaged. In the Milky Way, astronomers discovered the most primitive sugar molecule, glyceraldehyde (Fig. 1.4), and also N-methylformamide, in whose molecule the NH – CO bond typical of protein compounds occurs. Imaginative researchers therefore suspect that meteorites brought us the first building blocks of life from other planets from the vastness of space. An unnecessary assumption: Miller and his imitators have proven in thousands of experiments that the primordial soup also originated on earth. And three or four billion years should have been enough for evolution to develop all the forms of life that we find today. But even if we assume that the first living beings or their preforms, perhaps even just their genetic information, came to earth from space, that does not change the results of Miller’s experiments, except that the primordial soup in this case is somewhere else and even earlier originated. Wilhelm Busch is right when he writes: “Who can claim that natural laws are eternal? We only know one end of it. ”But there is also no reason to assume that they are not eternal.

1.4 From the amino acids to the protein Of the reaction products of the primordial soup, we are most interested in the amino acids. We are of course curious to wonder whether they are strong or weak acids. The acidic reaction, as we recall, is based on the fact that the hydrogen atom of the “carboxyl group” CO-OH tends to say goodbye leaving an electron behind, out of aversion to the oxygen atom of the CO group. This turns it into a positively charged hydrogen ion, also called a proton (the remaining CO – O group is negatively charged):

H2 N − CHR − CO − OH → H2 N − CHR − CO − O− + H +

6The best way to understand the enormous size of this number is to think of a machine that can count a million fixed stars per second. We turn it on and wait for it to finish counting. But that takes a long time, namely over 3 million years.

1 First excursion: a journey back in time

10

Amino acids are also bases, because their NH2 group tends to attach hydrogen ions to the nitrogen atom. As a result, the OH −- ions increase in aqueous solution, and they are responsible for alkaline or basic reactions: - -NH2 + HOH → -NH + 3 + OH

In the case of amino acids, the NH2 group can immediately attach the proton from its own molecule. This reduces the acid strength. Every amino acid can also be written as a hermaphrodite ion, which at first glance is neither acid nor base:

H3 N + −CHR − CO − O− And this means that amino acids are not strong acids. They are not strong bases either, for the same reason. Under physiological conditions, they are almost always present as hermaphrodite ions. Their most important property, however, is that they are able to react with one another in such a way that short or long molecule chains are created. They do this by creating a molecule of water from a hydrogen atom of the NH2 group of one amino acid and the OH group of a second amino acid. This releases binding forces on the two reactants. What could be more obvious than that they shake hands, so to speak - and this creates a new bond: R

R.

R.

H2N C C O H + H2N C C OH HO

R.

H2N C C NH C C O H + HO H

HO

HO

HO

A more complicated molecule has emerged, a “dipeptide”, in whose formula R stands for a hydrogen atom or a hydrocarbon radical, for example a methyl group (-CH3). But this dipeptide still has an NH2 group on one end and a CO – OH group on the other. It can therefore react further at both ends with a molecule of amino acid each with elimination of water and thus form a tetrapeptide of four units, as Fig. 1.6 shows. R1

R2

R3

R4

H2N C C NH C C O H + H2N C C NH C C O H H O

HO

HO

Dipeptide R1

HO

Dipeptide

R2

R3

R4

H2N C C NH C C NH C C NH C C OH + HOH H O

HO

HO

Tetrapeptide

Fig. 1.6 Further amino acid secondary products

HO

1.5 From the origin of life Fig. 1.7… an oligopeptide

11 H N

C.

O

H R2

C.

C.

H R1

N H

C O

H N

C.

O

H R4

C.

C.

H R3

N H

C O

H N

H R6

O C

C.

H R5

N H

C.

C O

The chain link NH – CHR – CO- is found in it four times in a row. That does not have to mean the end of the flagpole either, another amino acid molecule or many more could follow according to a tried and tested pattern. Different hydrocarbon radicals can stand for R within the same peptide molecule, which is represented in Fig. 1.7 by R1, R2, R3 and so on. In fact, one can find such “oligopeptides”, which are formed from a few, possibly even different, amino acids in the primordial soup. They tend to multiply "autocatalytically" in the primordial soup, because they attract amino acids with the help of intermolecular forces of attraction and hold them so skillfully that the groups of atoms that are supposed to react with one another come close.7 They are considered to be the "building blocks of life", because "Polypeptides", ie multi-part protein-like substances, can be obtained from them if they are heated to higher temperatures for some time together with catalysts or surface-active minerals. And how many amino acid chain links can be linked together in such a “protein”? That can be a few dozen, but also well over 100,000. When they are formed, however, water is split off from the raw materials and this does not work easily in the thin, watery primordial soup, much like it is not possible to make roasts in meat broth.

1.5 From the origin of life The researchers argue how and where real "polypeptides" or even protein lumps could be created from the oligopeptides. Perhaps on hot stones of volcanic origin that were splashed with primordial soup by surf waves at high tide and then fell dry at low tide. Or mineral catalysts, which allow an orderly deposition of reactive oligopeptides on their crystal surfaces and thus help to pre-shape the molecular structure of the protein molecule, so to speak. Maybe even at the hot springs in the deep sea! Or in hot crevices deep in the earth's crust. We don't know, and certainly not what the next steps up to the first primordial bacterium looked like - it is only certain that the way there was still a long way. However, the primordial soup also had a few hundred million years to find it.

7We will see later that many catalytic converters employ such security forces in their work.

12

1 First excursion: a journey back in time

1.6 Asymmetric Molecules and Optical Isomers Towards the end of this epoch, or perhaps shortly afterwards, a strange process probably took place. To understand it, let's look at the molecule of α-aminopropionic acid, also called alanine, as a representative of all amino acids involved in protein synthesis. If we look closely at the structural formula in Fig. 1.8, we notice that the carbon atom sitting in the middle of the tetrahedron has four different binding partners. Such a carbon atom is called an “asymmetric carbon atom” because you cannot cut it into two equal halves. Each half has different attachment partners! However, you can create a mirror image of this molecule if you attach the amino group where the hydrogen atom is in Fig. 1.8 and move it to the place of the amino group. In other words: If you let the hydrogen atom and the amino group swap places, as shown in Fig. 1.9. Our knowledge means that there must be two different alanine molecules that differ from one another like an image and a mirror image or like the right and left hand. The difference is minimal: it consists only in the arrangement of the binding partners. It is therefore obvious to you that both molecules contain the same amount of energy, which they give off when they are burned, for example. In the Haldane soup they will occur in the same amount, because there is no reason for one of the two “enantiomers” to arise preferentially. They do not differ in other ways either - for example in terms of melting point, solubility or reactivity. However, solutions of the two enantiomers rotate the plane of oscillation of polarized light, namely one clockwise and the other counterclockwise equally. For historical reasons we call the isomer of Fig. 1.8 “L-alanine” and that of Fig. 1.9 “D-alanine”. Easy to remember: If we set up the molecule so that the most oxygen-rich group is on top and the carbon chain runs down, then the larger ligand (i.e. the NH2 group) of the L connection is on the left. This also applies to other L-D enantiomers.

Fig. 1.8 Image ...

COOH H 2 N C H CH 3 L-alanine

Fig. 1.9 ... and mirror image

COOH H C NH 2 CH 3 D-alanine

1.8 Fiber proteins: wool and silk

13

1.7 Where were the D-amino acids? The strange process mentioned above led, for puzzling reasons, to an enormous excess of L-amino acids in the protein compounds and not only in them. D-amino acids, on the other hand, are so rare that they were not found at all for a long time. It was not until the early 1990s that they were discovered in some plants such as rice, garlic and peas, as well as in some antibiotics made by bacteria. Some process in the development of life must have led to protein compounds from L-amino acids being formed (or “survived”) much, much more frequently than their D-isomers. Fortunately, for our task of understanding biochemistry, we can leave this topic and return to the polypeptide molecular chain that we extracted from the oligopeptide in Fig. 1.7.

1.8 Fiber proteins: wool and silk We certainly agree that in the case of aminoacetic acid (glycine) as the starting product, the chain consists of many individual links with the structural formula

−NH − CH2 −CO−, as shown in Fig. 1.10. We now look around us somewhat concerned and ask whether there really are molecular chains with many thousands of such chain links. So that we do not need to Fig. 1.10 A polypeptide H H

NH C C O HN C

O C H H

NH C O C

O C

H

H

C HN

H

H

H H

NH C C O HN C

O C

H H

14

1 First excursion: a journey back in time

If we lose time in the search, we try to predict some properties of the protein body we are looking for from the structural formula, i.e. to create a profile of the natural substance we are looking for, and it works like this: Because these protein compounds consist of elongated molecular chains, they will also macroscopically tend to be long to form stretched threads. Billions of shorter or longer molecular chains are then twisted together in these threads, similar to, for example, the hemp fibers in a cord. We can expect such threads to be fairly tear-resistant, for two reasons: On the one hand, every molecular chain is extremely tear-resistant, because a covalent bond has to be torn apart when it is torn, and on the other hand, the individual molecular chains cannot easily slide past one another. They prevent electrostatic forces of attraction from doing so, because the oxygen atoms of the> C = O double bond pull the electrons closer to themselves than they should actually be, and the hydrogen atoms of the> NH bond also allow the nitrogen atoms to close the bond electrons a little more closely pull than they are actually entitled to. The result is that every hydrogen atom in the> N-H bonds has a positive partial charge and every oxygen atom in the> C = O groups has a negative partial charge. In every molecular chain, every> N-H group therefore holds a> C = O group in the neighboring chain by means of electrostatic attraction forces and every> C = O group holds a> NH group in the neighboring chain. It is also said that “hydrogen bonds” are formed between these groups of atoms. This hydrogen bond is by far weaker than a true homeopolar bond, but it is strong enough to create a certain order between the individual polypeptide chains and prevent them from sliding past each other. Instead, this fact leads to the creation of double strands of molecular chains, which consist of two single chains running in opposite directions and therefore offer double resistance to tearing (Fig. 1.11). And the attachment can be repeated on both sides of the double chain with the help of the hydrogen bridges, so that extremely tear-resistant ribbons or leaflets are created that can only be bent because they can be pushed against each other with almost no resistance - just like we would through the sheets of a block of paper Bending the same against each other can move. Because of the bond angle at the carbon atom, these leaflets are, if viewed more closely, folded leaflets. One therefore speaks of a β-sheet structure. Similar structures are created from paper when you bend a sheet of paper like an accordion. In addition to a primary structure - the polypeptide chain - our polypeptide has a secondary structure: the leaflet. The threads made of tear-resistant ribbons are very tensile because covalent bonds that each enclose angles of 109 ° have to be bent apart (you will probably remember this number that mathematicians gave us for tetrahedral bonds on the carbon atom). But what kind of thread are we talking about here? Which natural fiber is most similar to our polypeptide? A wool fiber or a cotton fiber? Another plant fiber like flax? Or a silk thread? A burn test helps us decide that.

1.8 Fiber proteins: wool and silk Fig. 1.11… with hydrogen bonds

15

H H

NH

C C O

HN C O C H H

H

H

H

C O NH

O C C

C O

O C

HN

H

H

H

H

NH

C O NH

O C C

C O C

O C

HN

H

H

H

H

H H

C.

C HN

H H

C.

C.

C.

H

HN

H

NH

HN

H

O C

C.

H H

C O C NH

Experiment 1.1: Combustion of natural fibers

We grab a small, loose cotton ball with tweezers and hold it in the flame of an alcohol burner. It burns quickly, odorless and without leaving a noteworthy residue (possibly a little ash). Other plant fibers, such as those found in linen threads or hemp cord, behave in a similar way. In contrast, wool burns more slowly. The flame goes out more easily and a burnt hair smell spreads. A blistering residue remains. A small bundle of natural silk threads behaves very similarly. Where do these differences come from? Cotton is practically pure cellulose, and it consists only of the elements carbon, hydrogen and oxygen. Burning therefore only produces carbon dioxide and water vapor. Both are odorless and gaseous at the moment of combustion. Since other plant fibers also only consist of C, H and O, they behave similarly to cotton when burned. At most, a very small amount of ash remains, which is usually noticeable as fine smoke (similar to cigarette smoke). In addition to the elements mentioned above, wool and silk also contain nitrogen. As the name suggests, it has a suffocating effect on living beings and fire. This is why a wool thread doesn't burn as quickly as cotton, the flame goes out more easily, a blistering residue is created and a smell of burned hair spreads. Our polypeptide chain from former

16

1 First excursion: a journey back in time

Aminoacetic acid molecules, just like wool or silk, also contain the four elements carbon, hydrogen, oxygen and nitrogen. It will burn like wool or natural silk. We can therefore exclude cotton and other plant fibers if we are looking for the natural substance that best fits the formula of our polypeptide.With another experiment we can detect the nitrogen in the polypeptides wool or silk:

Experiment 1.2: Detection of nitrogen in polypeptides

We produce a concentrated sodium hydroxide solution in a test tube by dissolving two granules of solid sodium hydroxide in 2 ml of water (Caution! It will heat up! Caustic soda chemical burns are dangerous, especially for the eyesight! Therefore, wear protective goggles and rubber gloves!). In this solution we boil a small bundle of woolen threads or hair for a few minutes. They gradually dissolve and there is a smell of ammonia and other nitrogen compounds. We prove it by holding a piece of damp pH paper in the vapor space with tweezers. It turns blue because the ammonia removes hydrogen ions from the water, creating hydroxide ions that increase the pH value: - HOH + NH3 → NH + 4 + OH

The experiment also works with silk thread or fingernail sections, but not with cotton or hemp cord. Why is ammonia created from protein compounds such as wool or silk? The caustic soda breaks down the NH – CO bond typical of polypeptides. When water accumulates, the polypeptide breaks down into the amino acids from which it was created. These are further attacked by caustic soda, with an OH group entering the molecule instead of the NH2 group and the CO – OH group being neutralized. Formulated using the example of aminoacetic acid, the reaction thus proceeds according to the following equations:

(-NH − CH2 −CO-) n + nHOH → nH2 N − CH2 −CO − OH H2 N − CH2 −CO − OH + HOH → HO − CH2 −CO − OH + NH3 HO − CH2 −CO − OH + NaOH → HO − CH2 −CO − O− Na + + HOH H2 N − CH2 −CO − OH + NaOH → HO − CH2 −CO − O− Na + + NH3 The reaction works with all protein compounds. In the case of fish or meat, it can also be easily carried out biochemically:

1.9 Read off macroscopic properties from structural formulas

17

Experiment 1.3: Biochemical decomposition of protein

We test a tiny piece of fish or meat that we have carefully washed with water with pH paper and convince ourselves that it has an almost neutral pH value (i.e. around 6 to 8). After a few days of keeping it in a sealed jam jar at room temperature, an unpleasant smell becomes noticeable. With moist pH paper, which we hold in close proximity over the sample, we detect ammonia (or amines, i.e. derivatives of ammonia) by means of blue coloration. The experiment also succeeds with ripening cheese.

1.9 Reading off macroscopic properties from structural formulas And what now? Wool or silk? The fascinating "silk gloss" is an almost proverbial term. He contributed to the fact that more than two thousand years ago silk was transported and traded by caravans on a road specially set up for this purpose over tens of thousands of kilometers, that it is mentioned in the Bible as a luxury commodity (Rev 18, 11-12). Nobody, on the other hand, praises the sheen of wool. The chain molecules of our invented polypeptide have no side chains. So the molecule is nice and smooth. We instinctively suspect that it forms shiny surfaces. The main contributor to the silky shine is the reflection of light on the structure of the leaves (the leaves act like mirrors!). This is also unlikely to develop easily with wool, probably because of the bulky side chains. So we decide on silk - we suspect that wool splits off many and different residues "R" from its molecular chains, does not form any leaflets and therefore has a much less sheen. Another observation speaks in favor of silk and against wool: Like our polypeptide, silk threads have a high tensile strength, while wool threads can be stretched before they break. The silk shirt becomes irrevocably too tight when we gain weight, while the wool sweater adapts elastically to the new shapes. And when the tension ceases, the woolen threads return to their original length, almost like elastic threads! (The fact that the silk shirt is woven and the wool sweater is knitted obviously adds to the difference). So silk! A silk thread actually consists mainly of former aminoacetic acid molecules that reacted with other amino acids to form a polypeptide or “polyamide”. Aminopropionic acid molecules are incorporated into the molecular chains somewhat less often, which then spread the methyl group to the side of the molecular chain, and the amino acid appears even more rarely alongside “glycine” and “alanine”

1 First excursion: a journey back in time

18 H H N H

C.

C O

H N

C.

O

H H

C.

C.

H CH 2

N H

C O

H N

C.

O

H H

C.

C.

H CH 3

N H

C O

H N

H H

O C

C.

H CH 3

N H

C.

C O

OH glycine

Serine

Glycine

Alanine

Glycine

Alanine

Glycine

Fig. 1.12 silk!

Serine with a side group H-O-CH2-. So all three have no or short side chains and alternate in the order presented here:

Incidentally, (-Gly-Ser-Gly-Ala-Gly-Ala-) n cobwebs have a similar structure - they too are shiny and amazingly tensile and tear-resistant. Fig. 1.12 shows the sequence of the amino acids in the silk in more detail. Uff! After just a few pages of exhausting reading, we succeeded in reading mechanical and optical properties from a structural formula!

1.10 Man-made fibers, which are also polyamides We look down at the plastics chemists with pity because they imitate this bond principle with their “nylon 6”, also called “Perlon 6”, “polyamide 6” or “polycaprolactam” - only that they have six carbon atoms in a chain where two are sufficient for silk.8 They logically designate silk as “polyamide 2”, because regardless of the absent or present side chains R, only two carbon atoms follow each other in the peptide chain:

−NH − CHR − CO− But what happens to our molecular chain when, like wool, it is created from a wild mixture of different amino acids? And a little anxiously we ask ourselves whether “R” can possibly stand for an almost infinite number of different groups of molecules. In this case the biochemistry of the protein compounds would not be complicated, but infinitely complicated. Here, too, the answer reassures us, because it is that there are only 20 different amino acids in total that proteins can form. They are therefore also called “proteinogenic amino acids”. They are presented in Fig. 1.13. It is useful to divide them into "essential" and "non-essential" amino acids. The former must be supplied to the organism with food

8So

Chains in which the structure -NH − CH2 −CH2 −CH2 −CH2 −CH2 −CO- is repeated.

1.10 man-made fibers that are also polyamides

H

CH 3

Glycine

COOH H 2N C H

Alanine

COOH H 2N C H

CH 2

CH 2

OH

SH

COOH H 2N C H

COOH H 2N C H

COOH H 2N C H

CH 2

CH 2

C.

C.

C.

OH

Glutamic acid

COOH H 2N C H

COOH H 2N C H

CH 2

CH 2

CH 2

CH 2

CH 2

CH 2

CH 2 NH 3

Lysine COOH H 2N C H CH 2

O

NH 2

C.

O

OH

Asparagine

Aspartic acid

COOH H 2N C H

COOH H 2N C H CH 2

H 3C

CH CH 3

Valine

H 3C

CH CH 3

Leucine

NH H 2N

CH CH 3

Threonine

CH 2 O

HO

Cysteine

CH 2

NH 2

COOH H 2N C H

Serine

CH 2

Glutamine

+

COOH H 2N C H

CH 2 C

O

COOH H 2N C H

CH 2 NH

COOH H 2N C H

N

COOH H 2N C H

19

Histidine COOH H 2 N C H CH H 3 C CH 2 CH 3 isoleucine

+

NH 2

Arginine COOH H 2N C H CH 2

COOH H 2N C H CH 2

COOH H 2N C H CH 2

CH 2

H N

COOH proline

S CH 3

Phenylalanine

Methionine

OH

Tryptophan

Tyrosine

Fig. 1.13 The 20 protein formers

because he cannot make them himself. In humans, 8 amino acids are essential and 2 are "semi-essential" because they are only needed in certain situations - during growth and the recovery process. The remaining 10 can be tinkered with by the human body. Plants are much better biochemists: They do all 20 themselves.9 And it makes us think that apparently plants get along quite well without humans (and without animals), while we and all animals are dependent on plants.

9Man

has now discovered two more proteinogenic amino acids, namely pyrrolysine and selenocysteine. However, they are so rare that we can neglect them for the purposes of this introduction.

20

1 First excursion: a journey back in time

1.11 The versatile role of the side chains The versatility of the side groups R is astonishing for the chemist. There are those which consist only of carbon and hydrogen, such as the methyl group of alanine and the phenylmethyl group of phenylalanine. They make the protein water repellent when they predominate. If oxygen atoms are added to the side group R, they appear as OH groups or as COOH groups. The former make the protein water-friendly, according to the principle of “like and like people like to join together”, they can attach water molecules with the help of hydrogen bonds. The latter give the protein acidic properties because they tend to give off a hydrogen ion10. Amino groups, i.e. NH2 groups, on the other hand, lead to basic properties because they like to attach a hydrogen ion and, if this comes from a water molecule, leave behind the OH − ions typical of bases. But where do plants get the nitrogen they need for the synthesis of amino acids and proteins? Amazingly, not from the air, but from the ground. There you will find it in the form of salts, mostly nitrates, i.e. salts of nitric acid. Well-fertilized soil contains a sufficient amount of it, poorly fertilized soil too little. The plants thrive on the former and starve on the latter. Accordingly, the harvests are rich or meager. We understand why well-fertilized soils are essential for human nutrition. In principle, it does not matter whether the nitrate is offered directly to the crops in the form of a mineral fertilizer or whether it has to be created by microorganisms from urea, ammonium salts, manure, liquid manure, liquid manure or green manure. A wide field for prejudices and heated discussions! The farmer, who uses both organic and mineral fertilizers, obviously manages optimally. Record harvests are definitely not to be expected without mineral fertilizers. Incidentally, for the eight essential ones, there is the motto "Phenomenal Isolde sometimes tarnishes Lieutenant Valentin's lascivious dreams". You can easily remember the eight beginnings of words phenylalanine, isoleucine, threonine, methionine, leucine, valine, lysine and tryptophan. Always striving to make life as simple as possible for us, we discover two principles when we look closely at the 20 amino acid formulas: except for an amino group (-NH2) and a carboxyl group (-CO-OH), all have the characteristic group R on the carbon atom, that is adjacent to the CO-OH group. Biochemists refer to this carbon atom with the Greek letter α. And as a second law, we discover that the amino groups (-NH2) are also bound to the α-carbon atom. This makes it easier for us to describe such a polypeptide chain.

10 See

on this Dieter Neubauer “Kekulé's Dreams - Another Introduction to Organic Chemistry”, Springer Verlag Heidelberg 2014, p. 85.

1.12 How to describe a polypeptide

21

1.12 How to describe a polypeptide The biochemists have agreed on the following procedure: 1. You start on the left side of a piece of paper with the NH2 group, which is at one end of the polypeptide chain. They give the associated former amino acid the number 1. Its right neighbor is then the amino acid with the number two. This is followed by the one with the number three and so it continues until the last former amino acid, the CO – OH group of which forms the other end of the chain. If the polypeptide consists of 245 amino acids, the last amino acid has the number 245. 2. Each former amino acid link in the chain is described by an abbreviation. The most commonly used abbreviations are listed in Table 1.1. They either consist of three letters or (more modern) a single one. A very simple example shows how powerful the description is: The tetrapeptide chain Ala-Gly-Ser-Cys or A-G-S-C consists of alanine, glycine, serine and cysteine ​​and has the formula

H2 N − CHR1 −CO − NH − CHR2 −CO − NH − CHR3 −CO − NH − CHR4 −CO − OH Tab. 1.1 The abbreviations

Alanine

Ala

A.

Arginine

Arg

R.

Asparagine

Asn

N

Aspartic acid

Asp

D.

Cysteine

Cys

C.

Glutamine

Gln

Q

Glutamic acid

Glu

E.

Glycine

Gly

G

Histidine

His

H

Isoleucine

Ile

I.

Leucine

Leu

L.

Lysine

Lys

K

Methionine

Mead

M.

Phenylalanine

Phe

F.

Proline

Per

P.

Serine

Ser

S.

Threonine

Thr

T

Tryptophan

Trp

W.

Tyrosine

Tyr

Y

Valine

Val

V.

22 Fig. 1.14 The amide bond - mesomeric limit formulas

1 First excursion: A journey back in time H

H N C

N C O

O

where R1 = CH3 R2 = H R3 = CH2 −OH and R4 = CH2 −SH must be. In this molecule serine (Ser) has the number 3, written Ser 3, and cysteine ​​has the number 4, written Cys 4. What all proteins have in common…. It is the atomic grouping CO – NH or “acid amide group”, ie the grouping that has arisen from the amino group of one amino acid molecule and from the carboxyl group of another amino acid molecule by splitting off water. It is the link in the protein chain between the former amino acids that make up the polypeptide. We want to take a closer look at this atom grouping on the left-hand side of Fig. 1.14. In it we find everything that we expect based on our previous knowledge: a> C = O double bond that leaves the oxygen atom with two unbound electron pairs, a CN single bond and an> NH group that is attached to two carbon atoms with single bonds, carries a hydrogen atom, and still has a free pair of electrons left. However, this notation does not represent the actual facts perfectly. The oxygen atom has such a strong longing for electrons that it snatches an electron pair from the> C = O double bond and is thereby negatively charged. The carbon atom is now missing a pair of electrons. The nitrogen atom pityingly gives up its lone pair of electrons to fill the gap on the carbon atom. This creates a> C = N double bond and the nitrogen atom is positively charged (Fig. 1.14 right). Surely you already guessed that this picture also only incompletely depicts the actual facts. As is so often the case, the truth lies somewhere between the two representations, perhaps in the middle. Chemists usually indicate this with a double arrow ↔ which they place between the two extreme ideas. It is important for us, however, that the C – N bond obviously has a C = N double bond and therefore no longer allows it to rotate freely. Another consequence is then: The four atoms involved, C, H, N and O are all in one plane.11 Free rotation is only possible at the α-carbon atom. Here, for the first time, we encounter a situation that cannot be described with a single structural formula. The representation with two or more structural formulas, which are called “mesomeric limit formulas”, and which delimit the true state between two or more extremes, is also not entirely satisfactory.

11The

is easiest to see if you look at the two lines of the> C = CNH and> CO groups within the same helical molecule. They always strive in the longitudinal direction of the helix and occur regularly after an average of 3.6 -NH-CHR-CO chain links. The hydrogen bridges stabilize the spiral immensely because they act like vertical supports between the turns of a spiral staircase. This can be seen in Fig. 1.15. It shows the secondary structure of wool. But this stabilization has its limits, because we know that the hydrogen bond is much weaker than a real covalent bond (its binding energy is more than 10 times greater). If you pull on a wool thread, you tear such longitudinal hydrogen bonds and the coils stretch like in our wire experiment. If the tension is even higher, the spiral structure is even torn apart and the wool takes on a folded sheet structure like silk. When the tension subsides, the hydrogen bonds pull the filament back together to its original length.In the case of silk, we have learned, practically all> NH groups and all> CO groups are connected to one another by hydrogen bonds. With wool, on the other hand, many pay homage to idleness, because a hydrogen bond only begins after 3.6 amino acid chain links. The free> NH groups are useful for other purposes. They form a hydrogen bond to a water molecule when the wool comes into contact with water vapor. The free> CO groups do not want to stand back when it comes to holding water and do the same in their somewhat different way, as Fig. 1.16 shows so nicely. The result of this tethering between atoms of water and atoms of wool is the wonderful property of our woolen clothing that it absorbs up to 33% of its weight in water vapor and releases it again when it becomes increasingly dry, without feeling clammy or changing its other properties. However, if it is stretched vigorously, completely soaked, it gives up the spiral structure and takes on the folded leaf structure of silk. Then the elastic behavior is over and the wool sweater hangs on your body like a wet sack. Fortunately, everyone can find chain links

1.15 The role of hydrogen bonds

25

Fig.1.15 Wool

N

R.

N

R.

O

N N

O

R N

R.

O N

R.

O N

R.

O

N

O

R.

NO

R.

O O

Fig. 1.16 Wool and water

C O C

H

NH

H R2

C.

HN

O H

R1

C O

H + 3 H.

O

H

C O C

H R1

NH

H R2

H

C.

HN

HO

C O

H H O

After drying, it returns to its α-helix and the garment can once again pursue its main task of protecting us from cool drafts. Wonderful, isn't it? One more word about the side groups R of wool. They also contribute to the mechanical strength of wool by, for example, forming sulfur bridges between two helical polypeptide chains when two

26 Fig.1.17 Sulfur bridges

1 First excursion: A journey back in time O H H N C C

O H H N C C

CH 2 SH +

CH 2 S

- 2H

S.

SH

CH 2

CH 2 C O

C.

N H H

C O

C N H H

Side chains that come from cysteine ​​and therefore carry SH groups come close enough (Fig. 1.17). By the way, such sulfur bridges break when wool is ironed too hot or washed too hot. Because the sulfur bridges do not recede after excessive ironing or cooking, irreparable damage occurs, as housewives are reluctant to confirm. Even heteropolar, i.e. salt-like, bonds can occur if one side group carries a carboxyl group and the other an amino group. The CO-OH group then transfers a positively charged hydrogen atom to the amino group. It attaches this to the lone pair of electrons in nitrogen and thus forms a positively charged ammonium group, while the shamefully abandoned COO - group, understandably, remains negatively charged. The ionic bond is created as always, because negative and positive attract each other. It is similar to the ionic bond between Na + and Cl− in sodium chloride (table salt). The binding mechanism follows the model that ammonia and hydrogen chloride give off, because they are combined to form ammonium chloride according to the same principle (Fig. 1.18). Overall, the side groups pretty much completely fill the space between the helical loops.

1.16 A detour to bakeries and kitchens Speaking of sodium chloride! It actually has no place in sweet cake batter and almost nothing in bread batter. Nevertheless, bakers and housewives are reluctant to work in at least a pinch of table salt. A prejudice or an antiquated habit? Certainly not. Every flour contains protein molecules - for the most part the glue, also known as gluten, which is so dreaded by hypersensitive people. It gives the dough undesirable properties: insufficient elasticity when kneading, tendency to tear off the thin walls of the dough between the gas bubbles when the dough rises, sticking, of course, and and and ... macroscopic

1.17 hair

27 H N

O C

H CH 2 O

O

H N

C.

C.

C.

H

CH 2

CH 2

CH 2

C.

C.

OH

O

O

H

Polypeptide chain with glutamic acid as chain link H

N

H

H

+

H N H

CH 2 CH 2 CH 2

CH 2 CH 2

+ H

CH 2

H CH 2 N H

C.

C O

H CH 2 N H

C.

C O

Polypeptide chain with lysine as a chain link The two polypeptide chains pull each other because of the opposing O

electrical charge of the groups

and

C O