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Biochemistry Subject and Main Directions in Biochemistry Amino acids Peptides Proteins Professor E.V. Lukasheva Russian Peoples’ Friendship University Medical Faculty Department of Biochemistry Professor: Lukasheva Elena Vasilievna, Docror of biological sciences Лукашева Елена Васильевна Textbooks 1. Т.Т.Berezov, B.F. Korovkin «Biological Chemistry», М., Медицина, 1998. 2. «Биохимия» под ред. С.Е.Северина, М., Геотар-мед, 2003. 3. «Сборник тестов по биохимии», М., изд-во РУДН, 2004. 4. GARRETT&GRISHAM: http://web.virginia.edu/Heidi/home.htm Biochemistry Department is called by the name of Academician Berezov Temirbolat Tembolatovich (1924-2014) Founder of the biochemistry department, author of a textbook on biochemistry for medical students in Russia. Scientific work was devoted to the elaboration of anticancer therapy based on enzymes of microbial origin, which catabolize amino acids: L- asparaginase, methionine-gamma-lyase, L-lysine oxidase. Biochemistry investigates the molecular nature of life, including: 1. The chemical nature of the substances that make up living organisms. 2. Their transformation. 3. The relationship of these reactions to the activity of cells, organs, tissues. 4. The ways of affecting the biochemical processes in a living organism. Plan III- semester IV- semester Four colloquia Rank Three colloquia Examination Plan 1. On the stand of the Biochemical Department 2. At the web site of Lukasheva E.V.: РУДН Учебный портал Лукашева Елена Васильевна History of Biochemistry (b/c) B/c - a young science that has developed at the turn of 19th - 20th centuries. The term "biochemistry" was introduced by Carl Neuberg in 1903. BACKGROUND OF b/c – the development of organic chemistry and the discovery beginning the mid-18th century of large amount of organic molecules in plants and animals. Important stages of biochemistry origin are the synthesis of: 1828 - Urea (Wöhler*, Friedrich) 1845 - Acetic acid (A.Kolbe) 1854 - Fats (M.Bertlo) 1861 – Carbohydrates (Butlerov** A.M.) * Wöhler for the first time synthesized an organic compound from inorganic substances, thereby dealing a blow to the widespread vitalistic doctrine of a so-called life-force. ** Butlerov – the author of the theory of chemical structure of organic compounds. One of the streets nearby Russian Peoples’ Friendship University is called by his name. • Departments of Physiological Chemistry at medical Faculties of Russian Universities emerged in the late 19th century. Almost all the achievements have been made in biochemistry during 100 years !!!!! • Monthly – more than 50 biochemical journals are published and a lot of web editions. • The amount of information in biochemistry increases exponentially. Development of biochemistry in the 20th century 20-ies. - The discovery of many viruses and bacterial diseases 30-ies. - The science of nutrition, vitamins (molecular basis of scurvy, beri-beri, pellagra) 40-50-ies. - Hunting for enzymes (now known more 3000 enzymes ) 60-70-ies. - Hunting for genes Presently the main directions • • • • • Genetic engineering Biotechnololgy Bioenergetics Neurobiology (decoding brain activity) Metabolism in bone Our life is a continuous flow of chemical reactions 1. Digestion. 2. Absorption of substances in the intestine and their transport into cells. 3. Transformation of substances into CO2 and H2O with the energy accumulation in the form of ATP (catabolism). 4. Synthesis of proteins, carbohydrates, lipids, hormones and other substances (anabolism). 5. Muscle contraction. 6. Creation of the inter-membrane potentials. 7. Chemical processes of foreign substances (xenobiotics) neutralization. Biochemical reactions determine not only our health but also the vision of the world • Final reception - the processes in the central nervous system (poorly understood still) A wide area for investigation. • Smell, taste - special receptors bind to substances and transmit a signal to the central nervous system. • Vision is based on the cis-trans isomerization of retinal and dissociation of rhodopsin (retinal complex with the protein opsin) Cвязь эмоционального состояния с уровнем некоторых метаболитов и гормонов Эмоции Изменение уровня вещества Агрессивность ↑ серотонина Чувство комфорта, уверенности в себе ↑ глюкозы, NaCl, высших жирных кислот Повышение умственных способностей ↑ кофеина, мочевой кислоты (структурные аналоги пуринов) ↑ фенамина (структурный аналог фенилаланина) ↑ глицина Различные эмоции пептиды сна, молодости… Слабость, апатия ↓ тиреоидных гормонов (недостаток иода) Возбудимость, страстность ↑ (умеренное) тиреоидных гормонов Невыдержанность, агрессивность, невозможность сосредоточиться ↑ (быстрое и мощное) адреналина Эмоциональность, влюбленность, стремление к противоположному полу Половые гормоны Our sex is determined by the concentration of certain molecules DNA, hormones and their receptors – the main molecules responsible for manifestation of sexual characteristics The molecular logic of life Differences of wildlife from inanimate 1. Living creatures are characterized by high structural organization, both in space and in time. 2. Interaction of the metabolism and the environment. Extraction of energy from the external environment and its transformation. 3. As well the decay and synthetic processes proceed in the body constantly, intensively and simultaneously. 4. Тhe ability of the organisms to replicate. 5. The ability to self-regulate. What was the starting point of life evolution? Friedrich Engels believed that "life - a way of existence of protein bodies“ It is hard to put any class of compounds in the first place because of their functional importance: Lipids form a membrane and allow to separate the living organism from the environment. Academician Alexander Oparin in 1924 put forward the theory of the origin of life in the coacervate drops. Proteins are involved in the implementation of almost all functions in body (hormones, enzymes, transport proteins ...) Nucleic acids are important for the transmission and storage of hereditary information… Currently, the palm belongs to the RNA • NA can be synthesized naturally in certain conditions (lightning bolt) of simple molecules. In recent years it was found that NA can slowly catalyze both the reaction of their own synthesis and protein synthesis. Biochemistry is in close contact with: Molecular biology Bioorganic chemistry Pharmacology Pharmaceutical Chemistry Normal and pathological physiology Microbiology Dentistry Etc. Part II Amino acids (AA) – are low molecular weight compounds containing simulteneously amino and carboxyl group. ~ 300 AA have been discovered. • It was found that all the variety of proteins consists of approximately 20 amino acids, which are involved in ribosomal synthesis and called proteinogenic. All AA are amphoteric electrolytes, i.e. they may exhibit both acidic and basic properties The carboxyl group is acidic, it dissociates into ions in aqueous solution to give a proton and a negatively charged group COO¯ NH2- group has a basic character, it can bind hydrogen proton and become positively charged. In AA molecule proton from the carboxyl group may be transferred to amino group – forming the so called zwitter-ion. In solutions the amino acids are in the form of zwitter-ions. General properties of proteinogenic AA 1. They are α-amino acids, i.e. an amino group is located in the alpha position relative to the carboxyl group and the general formula is: H R C C NH2 OH O 2. Belong to L-amino acids All α-amino acids (except glycine) have an asymmetric carbon atom, possessing four different substituents. So they may have optical isomers. Optical isomers are designated by Latin letters. L- (from Lat. Louvus - left) and D- (from the Latin dexter - right). COOH COOH C R R C H2N H H NH2 Stereoisomers (chiral isomers) • All protein life on the earth is "left". There are "exceptions", but they only prove the rule. • It turns out that D-amino acids are extremely rare, but still occur. For example, they are present in the shell of anthrax (сибирская язва), which is therefore not degraded by enzymes which break the protein chain L-amino acids (proteinases). • D-AA are also found in some antibiotics and the cell walls of a number of bacteria and fungi. Letter symbols of amino acids Letter Amino acid Letter Amino acid A R N D C E Q G H I Ala Arg Asn Asp Cys Glu Gln Gly His Ile L K M F P S T W Y V Leu Lys Met Phe Pro Ser Thr Trp Tyr Val AA classification 1. According to the chemical nature of radical а) aromatic (Phe, Tir, Tri) b) branched (Val, Leu, Ile) c) cyclic non aromatic (Pro, His) d) sulphur-containing (Cys, Met) 2. According to the ability of groups in radicals to the polarization or dissociation а) non-polar, possessing in radical no groups, which are able to polarize or dissociate: glycine, alanine, valine, leucine, isoleucine, phenylalanine, methionine, proline, tryptophan. b) polar, possessing in radical: hydroxo–group – serine, threonine, tyrosine; sulphhydryl group – cysteine; amide group – asparagine or glutamine. c) charged, possessing in radical dissociating group: (+) charged lysine arginine histidine; (-) charged glutamate aspartate. 3. According to the affinity of side radicals to polar solvents, in particular water Hydrophilic 1. Polar 2. Charged (+) and (-) Hydrophobic Non-polar Ala, Leu, Phe, Trp,Ile, Val, Pro Amphiphilic Tyr Gly Met 4. According to the possibility of their synthesis in the body essential nonessential should be taken with food (are not synthesized in the body) are synthesized in the body Essential AA • • • • • • phenylalanine lysine arginine* histidine* methionine tryptophan • • • • valine# leucine# isoleucine# threonine * partially synthesized AA # - branched AA Proteins and peptides – polymeric molecules, consisting of amino acid residues Proteins are polypeptides with a molecular mass greater than 5,000 g / mol. Peptide bond A resonance structure is invoked to explain the rigidity of the peptide group. Optimal electron delocalization (π-bonding) within the peptide group depends upon the planar arrangement of these atoms. The partial double-bond character of the peptide bond is reflected in the intermediate length of the peptide bond relative to single and double carbon-nitrogen bonds. The peptide bond typically has a length of 1.32-1.33 Å (1 Å = 10−10 m), while the C–N bond in amines is typically ~1.49 Å, and the C=N bond of an imine is ~1.27 Å. Structural and functional diversity of proteins In how many ways can a chain of 20 different amino acids residues be collected? Number of variants: 2 × 10 raise to power18. But proteins have different polypeptide chain length and the same amino acid may be included several times. So, indeed, the variety of proteins may be tremendous. • • • • • Dipeptides1·2 Threepeptides 1 ·2 ·3 =6 Tetrapeptides1 ·2 ·3 ·4 = 24 Dekapeptides 3 628 800 10 AA), а из 20амк намного больше Если белок имеет всего 100 аминокислот в длину, то может существовать 20 в степени 100 вариантов его строения Hydrolysis • The peptide bonds are hydrolyzed in acidic or alkaline conditions as well as under the influence of certain enzymes, called proteinases (proteases, peptidases). This yields a mixture of peptides and amino acids. • Study of the products of partial and complete hydrolysis of peptides and proteins play is important for the understanding of their structure. Peptides Direct synthesis from amino acids catalyzed by enzymes Hydrolysis of proteins (specific proteolysis) Peptide hormones are formed by the specific proteolysis of their peptide precursors Peptids dithreetetraoligo- 10-15 AA poly - big peptides Proteins М.М. ≥ 5 000 Have a spatial structure In E.coli 3 000 proteins. In man more than 50 000. Proteomics – the study of big number of proteins simultaneously Some information about peptides • Among the peptides have a substance necessary for the body, and is - extremely poisonous. Peptides are many enzymes, hormones (substances that control activity of different cells). For example, water metabolism in the body controls the nonapeptide (9 amino acid residues vasopressin. Insulin - a peptide controlling sugar metabolism consists of two chains, one of which includes 21, and the other - 30 amino acid residues. The active principle of poison pale toadstool - dipeptides, snake venoms also contain peptides. Dipeptide aspartame - an artificial sweetener (200 times sweeter than his) There are natural polypeptides of 3000 times sweeter than sugar.