biochemistry(redirected from Biochemical analysis)
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See L. Stryer, Biochemistry (3d ed. 1988); C. K. Mathews and K. E. van Holde, Biochemistry (1990); G. Zubay, Biochemistry (3d ed. 1993).
The study of the substances and chemical processes which occur in living organisms. It includes the identification and quantitative determination of the substances, studies of their structure, determining how they are synthesized and degraded in organisms, and elucidating their role in the operation of the organism.
Substances studied in biochemistry include carbohydrates (including simple sugars and large polysaccharides), proteins (such as enzymes), ribonucleic acid (RNA) and deoxyribonucleic acid (DNA), lipids, minerals, vitamins, and hormones. See Carbohydrate, Deoxyribonucleic acid (dna), Enzyme, Hormone, Lipid, Protein, Ribonucleic acid (rna), Vitamin
Metabolism and energy production
Many of the chemical steps involved in the biological breakdown of sugars, lipids (fats), and amino acids are known. It is well established that living organisms capture the energy liberated from these reactions by forming a high-energy compound, adenosine triphosphate (ATP). In the absence of oxygen, some organisms and tissues derive ATP from an incomplete breakdown of glucose, degrading the sugar to an alcohol or an acid in the process. In the presence of oxygen, many organisms degrade glucose and other foodstuff to carbon dioxide and water, producing ATP in a process known as oxidative phosphorylation. See Carbohydrate metabolism, Lipid metabolism
Structure and function studies
The relationship of the structure of enzymes to their catalytic activity is becoming increasingly clear. It is now possible to visualize atoms and groups of atoms in some enzymes by x-ray crystallography. Some enzyme-catalyzed processes can now be described in terms of the spatial arrangement of the groups on the enzyme surface and how these groups influence the reacting molecules to promote the reaction. It is also possible to explain how the catalytic activity of an enzyme may be increased or decreased by changes in the shape of the enzyme molecule. An important advance has been the development of an automated procedure for joining amino acids together into a predetermined sequence. This technology will permit the synthesis of slightly altered enzymes and will improve the understanding of the relationship between the structure and the function of enzymes. In addition, this procedure permits the synthesis of medically important polypeptides (short chains of amino acids) such as some hormones and antibiotics.
A subject of intensive investigation has been the explanation of genetics in molecular terms. It is now well established that genetic information is encoded in the sequence of nucleotides of DNA and that, with the exception of some viruses which utilize RNA, DNA is the ultimate repository of genetic information. The sequence of amino acids in a protein is programmed in DNA; this information is first transferred by copying the nucleotide sequence of DNA into that of messenger RNA, from which this sequence is translated into the specific sequence of amino acids of the protein. See Genetic code, Molecular biology
The biochemical basis for a number of genetically inherited diseases, in which the cause has been traced to the production of a defective protein, has been determined. Sickle cell anemia is a striking example; it is well established that the change of a single amino acid in hemoglobin has resulted in a serious abnormality in the properties of the hemoglobin molecule. See Disease
Increased understanding of the chemical events in biological processes has permitted the investigation of the regulation of these proceses. An important concept is the chemical feedback circuit: the product of a series of reactions can itself influence the rates of the reactions. For example, the reactions which lead to the production of ATP proceed vigorously when the supply of ATP within the cell is low, but they slow down markedly when ATP is plentiful. These observations can be explained, in part, by the fact that ATP molecules bind to some of the enzymes involved, changing the surface features of the enzymes sufficiently to decrease their effectiveness as catalysts. It is also possible to regulate these reactions by changing the amounts of the enzymes; the amount of an enzyme can be controlled by modulating the synthesis of its specific messenger RNA or by modulating the translation of the information of the RNA molecule into the enzyme molecule. Another level of regulation involves the interaction of cells and tissues in multicellular organisms. For instance, endocrine glands can sense certain tissue activities and appropriately secrete hormones which control these activities. The chemical events and substances involved in cellular and tissue “communication” have become subjects of much investigation.
Photosynthesis and nitrogen fixation
Two subjects of substantial interest are the processes of photosynthesis and nitrogen fixation. In photosynthesis, the chemical reactions whereby the gas carbon dioxide is converted into carbohydrate are understood, but the reactions whereby light energy is trapped and converted into the chemical energy necessary for the synthesis of carbohydrate are unclear. The process of nitrogen fixation involves the conversion of nitrogen gas into a chemical form which can be utilized for the synthesis of numerous biologically important substances; the chemical events of this process are not fully understood. See Nitrogen cycle, Photosynthesis
biological chemistry, the science dealing with the composition of organisms; the structure, properties, and localization of compounds observed in organisms; the pathways and laws governing the formation of these compounds; and the sequence and mechanisms of transformations and their biological and physiological roles. Biochemistry is subdivided into the biochemistry of microorganisms, of plants, of animals, and of man. This subdivision is arbitrary, since there is much in common in the composition of the various objects of study and in the biochemical processes taking place in them. For this reason, the research carried out on microorganisms complements and enriches research on plant or animal tissues and cells. Although the different branches of biochemical research are intimately connected, it is accepted practice to divide biochemistry into static biochemistry, concerned predominantly with the analysis of the composition of organisms; dynamic biochemistry, concerned with the transformation of substances; and functional biochemistry, which elucidates the chemical processes that underlie various manifestations of the life functions. The last branch of research is sometimes referred to by the special name “physiological chemistry.”
The totality of chemical reactions taking place in an organism, from the acquisition of materials which enter the organism from without (assimilation) and their breakdown (dissimilation) to the formation of the end products that are secreted, constitutes the essence and content of metabolism—the main and constant criterion of all living things. Understandably, the study of metabolism in all its details is one of the major tasks of biochemistry. Biochemical research embraces a very wide range of questions: there is no branch of theoretical or applied biology, chemistry, or medicine which is not linked with it. Thus, contemporary biochemistry unites many related scientific disciplines that became independent in the middle of the 20th century.
The accumulation of biochemical information and establishment of biochemistry in the 16th to 19th centuries. Biochemistry took shape as an independent science at the end of the 19th century; however, its origins reach far back into the past. From the first half of the 16th century until the second half of the 17th century, iatrochemists (chemistphysicians) made their contribution to the development of chemistry and medicine: the German physician and natural scientist P. Paracelsus, the Dutch scholars J. B. van Heimont and F. Sylvius, and others studied the digestive juices, bile, and the processes of fermentation. Sylvius, a famous physician, attributed particularly great importance to the correct balance of acids and alkalies in the human organism; he believed that many if not all diseases were caused by a disturbance of this balance. Many of the positions espoused by the iatrochemists were naive and entirely mistaken; however, it must not be forgotten that chemistry did not yet exist at that time. The most generally accepted theory governing science at that time was the so-called phlogiston theory. Nevertheless, equilibrium experiments were carried out on man with exact records of body mass and secretion by the Italian scientist S. Santorio at the beginning of the 17th century. These experiments led to the description of perspiratio insensibilis—the loss of mass owing to “insensible perspiration.”
The great discoveries in the areas of physics and chemistry in the 18th and beginning of the 19th centuries (the discovery of many simple substances and compounds, the formulation of the gas laws, the discovery of the laws of conservation of matter and energy) laid the scientific foundation of general chemistry. After the discovery of oxygen as a component of air, the Dutch botanist J. Ingenhousz was able to describe the continual formation of CO2 by plants and the release of oxygen by the green parts of the plant stimulated by sunlight. Ingenhousz’ experiments marked the beginning of the study of plant respiration and the processes of photosynthesis, which are still being explored in detail.
At the end of the first quarter of the 19th century, only a very small number of organic substances were known. In the textbook of the German chemist L. Gmelin published in 1822, only 80 organic compounds are named. At that time the tasks and possibilities of organic chemistry were still unclear. The Swedish scientist J. Berzelius thought that organic bodies were divided into two clearly differentiated classes—plants and animals; he also thought that the essence of living matter derived from something other than its inorganic elements. This something else, which he called life force, lies entirely beyond the realm of inorganic elements. Berzelius expressed doubt that man will ever be able to produce organic substances artificially and confirm such analysis by synthesis (1827). The untenability of these views, which were typical of vitalism, was demonstrated very shortly. As early as 1828, the German chemist F. Wöhler, a student of Berzelius, produced urea by synthetic means. Urea had been described in the 18th century by the French scientist H. Rouelle as one of the component parts of urine in mammals. Soon there followed the synthesis of other natural organic compounds and of artificial compounds unknown in nature. Thus, the wall separating organic from inorganic compounds was broken down.
Beginning with the second half of the 19th century, organic chemistry increasingly became synthetic chemistry, within which efforts were directed at the preparation of new carbon compounds, especially those having industrial use. The study of the composition of plant and animal specimens was not yet included. Knowledge in this area was obtained by chance as a by-product of work by chemists, botanists, plant and animal physiologists, pathologists, and physicians whose interests included chemical research. Thus, in 1814, the Russian chemist K. S. Kirkhgof described the conversion of starch into sugar under the effect of extract of sprouted barley seeds—the action of amylase. By the middle of the 19th century, other enzymes were described: salivary amylase, which breaks down polysaccharides; and pepsin in gastric juice and trypsin in the pancreatic fluid, which break down protein. Berzelius introduced the concept of catalysts into chemistry and included all enzymes known at that time in this category. In 1835 the French chemist M. Chevreul described creatine in muscle tissue; shortly thereafter, the structurally related creatinine was discovered in urine. The German chemist J. von Liebig established the presence of lactic acid in the skeletal muscles and the accumulation of this substance during work. In 1839 he established that food was composed of protein, fats, and carbohydrates, which are the main components of animal and plant organisms. In the mid-19th century the structure of fat was established and its synthesis was carried out by the French chemist P. Berthelot; the synthesis of carbohydrates was accomplished by the Russian scientist A. M. Butlerov, who also proposed a theory of the structure of organic compounds that retains its importance even today. The systematic study of proteins was begun by the Dutch physician and chemist G. J. Mulder in the 1830’s and has continued intensively ever since. At the same time, in connection with the description of yeast cells (C. Cagniard de La Tour in France and T. Schwann in Germany, 1836–38), scientists began actively studying the process of the metabolism of sugar and formation of alcohol, which had long since attracted attention. Among those who studied fermentation were J. von Liebig and the French scientist L. Pasteur. Pasteur came to the conclusion that fermentation was a biological process that required the participation of living yeast cells. Liebig, on the other hand, regarded the metabolism of sugar as a complicated chemical reaction. This dispute was resolved when the Russian chemist M. M. Manassein (1871) and, with even more clarity, the German scientist E. Buchner (1897), proved the ability of the fluid extracted from yeast cells to induce alcoholic fermentation. Thus, the correctness of the chemical theory of enzyme action formulated by Liebig in 1870 was confirmed; the basic principles of this theory have retained their importance to this day.
A significant quantity of information accumulated regarding the chemical composition of plant and animal organisms and the chemical reactions taking place in them; at the same time, attempts were made to systematize and organize this information in treatises. The earliest of these were the textbooks of J. Simon (1842) and of Liebig (1847), published in Germany; and the textbook of physiological chemistry by A. I. Khodnev, issued in Russia (1847).
The origin and development of contemporary trends in biochemistry. At the end of the 19th century and during the 20th century, the development of biochemistry took on a markedly specialized character which reflects the problems and the objects of study. Plant biochemistry developed predominantly in subdepartments of botany and of plant physiology. The biochemistry of microorganisms is also closely related to plant biochemistry. Biochemists of all countries have studied proteins, carbohydrates, lipids, and vitamins (the component parts of plants, animals, and microorganisms) in the most varied specimens.Glycosides, tanning agents, essential oils, alkaloids, antibiotics, and other so-called secondary products can be regarded as characteristic of plants and microorganisms. Among the above mentioned compounds, many glycosides were synthesized by enzymes by the French chemist E. Bourquelot and his coworkers (1911–18). The classic work of the German chemist R. Willstatter (1910–15) played an exceptional role in deciphering the structure of the anthocyanins—the glycosides that make up the pigments of flowers and fruits. The German chemist A. Hofmann (1890–1900) studied the group of alkaloids (nitrogenous heterocyclic substances of fundamental character). Later, other outstanding researchers studied the alkaloids (R. Willstätter, the Russian chemists A. P. Orekhov and A. A. Shmuk, and many others). Leading chemists and biochemists—Perkin, Jr. (Great Britain), H. Euler (Sweden), and others—also successfully studied the essential oils and the terpenes.
An outstanding role in the development of plant biochemistry in Russia (at the end of the 19th century and during the first half of the 20th century) was played by Professor A. S. Famintsyn of the University of St. Petersburg and his students D. I. Ivanovskii (who discovered viruses) and I. P. Borodin (who studied the oxidation processes in plant organisms and their relation to protein transformation).
The work of S. P. Kostychev (professor at the University of St. Petersburg—later, Leningrad State University) on anaerobic carbohydrate metabolism and plant respiration enriched chemical physiology by the discovery of new intermediates in fermentation and by the formulation of original views on the nature of oxidation processes, protein metabolism, and nitrogen fixation by plants. M. S. Tsvet, professor at the University of Warsaw, made a significant contribution with his column chromatography method, which is still used today. The Moscow school of physiologists and plant biochemists was represented by K. A. Timiriazev, who studied photosynthesis and the chemistry of chlorophyll. His students—V. I. Palladin, who worked on biological oxidation; D. P. Prianishnikov, who studied nitrogen metabolism in plants; V. S. Butkevich, who enriched theoretical biochemistry with his research on protein and protein metabolism in plants; and A. R. Kizel’, who studied arginine and urea metabolism in plants and structural elements in cell protoplasm—were the founders of the great schools and original directions in contemporary general and evolutionary biochemistry, and also of physiology and plant biochemistry, which developed fruitfully in the last 25 years of the 20th century. In the 20th century, researchers in the biochemistry of microorganisms and plants solved many common problems involving natural compounds (including macromolecules), their structures and paths of formation and breakdown, and the properties of enzymes participating in these processes. It should be noted that microorganisms gradually became the favorite specimens for various enzymological studies and for the solution of problems in biochemical genetics.
All this research created a firm foundation for the solution of many specific problems, including industrial problems. Among the latter were the production of new antibiotics, the development of methods for purifying them, and the search for conditions favorable to the microbiological synthesis not only of antibiotics but also of other biologically active compounds—vitamins, critical amino acids, nucleotides, and so on.
TECHNICAL AND INDUSTRIAL BIOCHEMISTRY. the requirements of the national economy—problems of profitable production of raw materials and their practical and rational storage, correct processing, and effective use; problems of raising the yield of cultivated plants; questions of viticulture and the technology of wine-making; and the requirements of the food industry—have led to the creation of a new branch of biochemistry: technical and industrial biochemistry. In the USSR, this area is represented most strongly by the A. N. Bakh Institute of Biochemistry (A. I. Oparin, V. L. Kretovich, L. V. Metlitskii, R. M. Feniksova, and others) and the Institute of Plant Physiology of the Academy of Sciences of the USSR (A. L. Kursanov and his coworkers and students). I. P. Ivanov (All-Union Institute of Plant-Growing), V. L. Kretovich, M. I. Kniaginichev, their coworkers, and many others have greatly contributed to the study of the biochemistry of grain crops. The work carried out at the A. N. Bakh Institute on the Biochemistry of Catechins has played an important role in the development of production of tea and tanning agents.
ANIMAL AND HUMAN BIOCHEMISTRY (MEDICAL AND PHYSIOLOGICAL CHEMISTRY). The development of animal and human biochemistry has been greatly furthered by the numerous groups of physiologists, chemists, pathologists, and medical doctors working in different countries. In France, in the laboratory of the physiologist C. Bernard, glycogen was discovered in the liver of mammals (1857) and the pathways of its formation and the mechanisms regulating its breakdown were studied; also in France, L. Corvisart (1856) discovered the enzyme trypsin in pancreatic juice. In Germany, F. Hoppe-Seyler, A. Kossel, E. Fischer, E. Ab-derhalden, O. Hammarsten, and others made detailed studies of simple and complex proteins, their structure and properties, and the substances formed by artificial degradation upon heating with acids and bases or by the action of enzymes. In England, F. Hopkins, the founder of the Cambridge school of biochemists, investigated the amino acid composition of proteins, discovered tryptophan and glutathione, and studied the role of amino acids and vitamins in nutrition.
Russian scientists working in the departments of higher academic institutions and in specialized institutes made an important contribution to the development of biochemistry at the turn of the 20th century. In the Military Medical Academy, A. la. Danilevskii and his coworkers studied problems of protein chemistry, methods for isolating and purifying enzymes, mechanisms of enzyme action, and the conditions for reversibility of enzyme reactions. At the Institute for Experimental Medicine, M. V. Nentskii carried out research on the chemistry of porphyrins and the biosynthesis of urea, and also on bacterial enzymes which are responsible for the breakdown of amino acids. The collaboration of the laboratories of A. la. Danilevskii and M. V. Nentskii with the laboratory of I. P. Pavlov in research on digestion and the formation of urea in the liver was especially fruitful. At Moscow University, V. S. Gulevich conducted detailed and successful research into extractive (nonprotein) substances present in muscle and discovered many new nitrogencontaining compounds of unique structure (carnosine, carnitine, and others). The detailed study of the various enzyme reactions which take place in the parenchymatous organs—mainly in the liver—and which govern the normal course of transport processes has been and remains the object of much research. In the second half of the 19th century and during the 20th century, much attention has been devoted to the biochemical study of excitable tissue, predominantly of the brain and muscle. In the USSR, A. V. Palladin, G. E. Vladimirov, E. M. Kreps, and their students and coworkers have worked on these problems. By the middle of the 20th century, neurochemistry had become one of the independent branches of biochemistry. The biochemistry of the blood was studied comprehensively. The respiratory function of the blood (that is, the binding and release of carbon dioxide and oxygen by the blood) was studied in the laboratory of C. Ludwig in Vienna in the mid-19th century and later in greater detail in various countries. The data obtained led to the analysis of the structure and properties of hemoglobin in its normal and pathological states, the detailed study of the reaction between hemoglobin and oxygen, and the elucidation of the laws governing the acidbase balance.
Biochemistry achieved great success in the study of vitamins, hormones, and mineral substances, and especially of trace elements, their distribution in various organisms, their physiological roles, the mechanisms of their action, and their regulating influence on enzyme reactions and transport processes. Of great importance is the question of the relation between structure and function, which characterizes the problems of biochemical pharmacology in dealing with medicinal preparations; and the study of the primary mechanism of their action, which involves intervention in the enzyme reactions that form the basis of the metabolic processes. In the mid-20th century, biochemical research carried out in clinics and devoted to the study of the biochemical features of the organism and the chemical makeup of blood, urine, and other fluids and tissues of the patient acquired an independent status. This area, which received extensive development, is the basis of clinical biochemistry.
VITAMINOLOGY. In 1880, in G. A. Bunge’s laboratory, a young Russian physician named N. I. Lunin first described the supplementary nutrient factors found in milk. Similar observations were made by the Dutch physician C. Eijkman, who in 1896 described the presence of a vital factor in rice bran. In 1912, the Polish researcher C. Funk isolated the active component in crystalline form and called it a “vitamin.” Work in this area was greatly expanded, and gradually many other vitamins were discovered. Today, vitaminology is one of the most important branches of biochemistry and of nutrition.
BIOCHEMISTRY OF HORMONES. Research on the analysis of the chemical structure of the products of glands of internal secretion (hormones), the pathways of their formation in the organism, their modes of action, and the possibility of synthesizing them in the laboratory constitutes one of the most important areas of biochemical research. The biochemistry of steroid hormones is part of the general problem of the biochemistry of sterines. The successes achieved in this area are largely a result of the use of initial and intermediate compounds labeled with carbon (14C). A close relationship has been established between a wide range of research on protein substances and the specialized study of the structure and function of hormones of proteinlike character. The study of the hormone activity of a given preparation is impossible without a thorough analysis of the biochemical mechanisms governing its activity. Thus, data concerning the chemistry and biochemistry of hormones contribute equally to our knowledge of endocrinology and of biochemistry.
ENZYMOLOGY. The study of enzymes is an entirely independent area of biochemistry. In this field, the problem of the structure of enzymatic proteins is closely interwoven with physicochemical problems of chemical kinetics and catalysis. In the second half of the 20th century, much new information has been added to our conception of enzyme structure and of their presence in the natural state in the form of complexes. The analysis of enzyme structure in conjunction with the activity exhibited by enzymes under various conditions has led to the understanding of the role of individual amino acids (mainly cysteine, lysine, histidine, tyrosine, and serine) in the formation of the active sites of enzymes. The structure of many coenzymes has been determined along with their significance for enzyme activity and also the relation between coenzymes and vitamins. R. Willstätter, L. Michaelis, G. Embden, and O. Meyerhof (Germany), J. Sumner and J. Northrop (Usa), H. Euler (Sweden), and A. N. Bakh (USSR) all made important contributions to the development of enzymology during the first half of the 20th century. Those who actively continued their research, set up schools, and opened up new areas include O. Warburg (West Berlin) and F. Lynen (Federal Republic of Germany), R. Peters and H. Krebs (Great Britain), H. Theorell (Sweden), F. Lipmann and D. Koshland (USA), F. Sorm (Czechoslovakia), F. Straub (Hungary), and T. Baranowski and J. Heller (Poland). In the USSR, the field of research is represented by V. A. Engel’gardt and M. N. Liubimova, who established the enzyme activity of muscle protein and, in particular, the adenosine triphosphate activity of myosin and the process of oxidative phosphorylation; A. E. Braunshtein, who, in collaboration with M. G. Kritsman, discovered the process of the transfer of an amino group; A. I. Oparin and A. L. Kursanov, who studied the role of cell structure in the manifestation of enzyme activity; and S. R. Mardashev, who successfully studied the decarboxylation of amino acids. Research on large complexes of enzymes is being conducted in the laboratories of L. Reed (USA), M. Koike (Japan), D. Sanadi (USA), F. Lynen (West Germany), S. E. Severin (USSR), and others. The Soviet scientist V. A. Belitser greatly furthered our understanding of the efficiency of the role played by respiration—discovered by V. A. Engel’gardt—in the formation of energyrich compounds; G. E. Vladimirov specified the quantity of energy (10 calories, or 42 joules) liberated by the hydrolysis of ATP. Studies in this area were isolated at first, but in the 1950’s and later, work was greatly expanded, largely owing to research by D. Green, B. Chance, A. Lehninger, and E. Racker (USA), and E. Slater (Netherlands). In the USSR, this problem has been studied in the biochemistry sub-departments at Moscow State University and Leningrad State University, and also in independent laboratories (S. A. Neifakh, V. P. Skulachev, and others). In addition, contemporary research has demonstrated the marked influence of the salt content of the surroundings and of individual ions on enzymatic processes and the important role of trace elements in the realization of enzyme activity.
EVOLUTIONARY AND COMPARATIVE BIOCHEMISTRY. Studies of the chemistry of animals, plants, and microorganisms have shown that, in spite of the universality of basic biochemical structures and processes in all living organisms, there are specific differences determined by the level of ontogenetic and phylogenetic development of the specimen under examination. The accumulation of facts has provided the foundation for comparative biochemistry, whose object is to find the laws governing the biochemical evolution of organisms. In this connection, the problem of the origin of life on earth has great theoretical importance. Several important hypotheses of A. I. Oparin’s theory on the origin of life have received experimental confirmation in work done at the Bakh Institute, in the Subdepartment of Plant Biochemistry at Moscow State University, and in many foreign laboratories (for example, J. Oro and S. W. Fox in the USA).
HISTOCHEMISTRY AND CYTOCHEMISTRY. With the development of the techniques of morphological research, and especially with the introduction of the electron microscope—which revealed many formerly unknown structures in the cell nucleus and protoplasm—into laboratory work, new tasks presented themselves to biochemistry. On the borderline between morphological and biochemical research new areas of study have grown up. These include histochemistry and cytochemistry, which study the localization and transformation of substances in cells and tissues using biochemical and morphological methods.
BIOORGANIC CHEMISTRY. the detailed investigation of the structure of biopolymers—simple and complex proteins, nucleic acids, polysaccharides, and lipids—and the analysis of the effects of biologically active small molecular natural compounds (coenzymes, nucleotides, vitamins, and so on) led to the necessity of studying the relationship between the structure of a substance and its biological function. The formulation of this problem brought about a proliferation of research carried out on the border between biological and organic chemistry. This research area received the name of bioorganic chemistry.
MOLECULAR BIOLOGY. the development of methods for separating subcellular structures (ultracentrifugation) and for obtaining separate fractions containing the cell nuclei, mitochondria, ribosomes, and so on made possible the detailed study of the composition and biological functions of the separated components. The application of the methods of electrophoresis in conjunction with chromatography made possible the detailed characterization of macro-molecular compounds. The parallel development of analytic determination permitted the analysis of very small quantitites of mate-erial. This advance was linked to the introduction of physical (mainly optical) methods of analysis into biology and biochemistry (fluorometry, spectrophotometry in various regions of the spectrum, mass spectrometry, nuclear magnetic resonance, electron paramagnetic resonance, and gas and liquid chromatography), with the use of radioactive isotopes; sensitive automatic analyzers of amino acids, peptides, and nucleotides; polarimetry; macromolecular electrophoresis; and other methods. These developments led to the appearance of yet another independent branch of biochemistry, closely related to biophysics and physical chemistry, called molecular biology.
MOLECULAR GENETICS. Molecular genetics, in spite of some of its specific objectives, can be considered a part of molecular biology. Thus, for example, the analysis of the mechanism governing the occurrence of many hereditary malfunctions in the metabolism and actions of an organism has made possible the clarification of the role of the cessation or modification of the biosynthesis of those protein substances which have enzymic, immunological, or other biological activity. In this connection, the study of disruptions in the metabolism of carbohydrates and amino acids (for example, phenylalanine, tyrosine, and tryptophan) and the formation of pathological forms of hemoglobin and other biological compounds are relevant.
The development of new research methods between 1950 and 1970 has produced great advances in biochemistry. Foremost is the elucidation of protein structure and the determination of the sequential arrangement of amino acids within proteins. The first sequential arrangement of amino acids in the proteinlike hormone insulin was worked out by the English biochemist F. Sanger; later, the structure of the enzyme ribonuclease was determined by C. Hirs, S. Moore, and W. Stein (USA), who devised the method of automatic analysis of amino acids which became standard in biochemical laboratories. The same enzyme, ribonuclease, obtained from various sources was studied by C. Anfinsen (USA), F. Egami (Japan), and others. F. Sorm, B. Keil, and their coworkers (Czechoslovakia), B. Hartley (Great Britain), and others established the sequential arrangement of amino acids in many proteolytic enzymes. A major achievement of the 1960’s was the chemical synthesis of hormones—the adrenocorticotropic hormone, a molecule containing 23 amino acids (the natural hormone has 39 amino acids), and insulin, a molecule made up of 51 amino acids—and of the enzyme ribonuclease (124 amino acids).
In the USSR, work on problems of structure and synthesis of biologically active substances is being pursued at the Institute for the Chemistry of Natural Compounds (director, M. M. Shemiakin), at the Institute of Biological and Medical Chemistry (director, V. N. Orekhovich), and at other institutes and university departments.
The English scientists M. Perutz and J. Kendrew and their coworkers used X-ray analysis with great success in the determination of the structure of myoglobin and hemoglobin. In 1956 and 1957 the entire structure of lysozyme was worked out by the English biochemist D. Phillips and others. Equally important successes were achieved in the analysis of complex proteins, nucleoproteins, nucleic acids, and nucleotides. The triumphal accomplishment of biochemistry, molecular biology, and genetics was the research which established the role of nucleic acids in the biosynthesis of proteins and the predetermining influence of nucleic acids on the structure and properties of proteins synthesized within cells. This work elucidated the biochemical basis of the transmission of traits by inheritance from one generation to another. It is also difficult to overestimate the importance of the research which determined the sequence of nucleotides in transfer RNA (ribonucleic acid) and the elaboration of methods for the organic synthesis of polynucleotides. The work of the following investigators has been especially fruitful in the aforementioned areas: J. Buchanan, E. Chargaff, J. Davidson, D. Davis, A. Kornberg, S. Ochoa, J. Watson, and M. Wilkins (USA); F. Crick and F. Sanger (Great Britain); F. Jacob and J. Monod (France); and A. N. Belozerskii, A. S. Spirin, V. A. Engel’gardt, and A. A. Baev (USSR).
Scientific institutions, societies, and periodicals.. The questions addressed to biochemistry by related scientific disciplines—medicine and all its branches, agriculture (plant-growing and livestockraising), the food industry, theoretical and applied biology, soil science, hydrobiology, and oceanology—are continually increasing in scope. Each special field of biochemistry, in the USSR and abroad, utilizes a network of specialized institutes and laboratories. In the USSR, scientific work in biochemistry is conducted in central scientific research institutes within the various systems: in the Academy of Sciences of the USSR—the A. N. Bakh Institute of Biochemistry, the Institute of Evolutionary Physiology and Biochemistry, the Institute of Plant Physiology, the Institute of Molecular Biology, the Institute of the Chemistry of Natural Compounds; in academies of the various republics—the Institute of Biochemistry of the Ukrainian SSR, the Armenian SSR, the Uzbek SSR, and the Lithuanian SSR; in branch academies—the Institute of Biological and Medical Chemistry of the Academy of Medical Sciences of the USSR, the Biochemistry Department of the Institute of Experimental Medicine of the Academy of Medicine of the USSR, the Institute of Experimental Endocrinology and Hormone Chemistry of the Academy of Medical Sciences of the USSR, and the Institute of Nutrition of the Academy of Medical Sciences of the USSR; and in the institutes of the All-Union Academy of Agricultural Sciences and of many ministries (ministries of health, agriculture, food industry, and so on). Research in biochemistry is conducted in the bioorganic chemistry laboratory at Moscow State University and in many university subdepartments of biochemistry. Problems of biochemistry are studied in the central and branch institutes devoted to areas of botany, physiology, and pathology and in institutes of experimental and clinical medicine, the food industry, physical culture, and many other institutes. Most specialists in biochemistry, both in the USSR and abroad, are trained in universities, where the faculties of chemistry and biology contain specialized departments. Biochemists with a more limited background are trained in medical, technical, agricultural, and other institutions.
In the majority of countries, there are scientific biochemical societies united under the Federation of European Biochemical Societies and the International Union of Biochemistry. These organizations hold symposia and conferences, and also congresses—yearly in the case of the Federation of European Biochemical Societies (the first took place in 1964), and once every three years in the case of the International Union of Biochemistry (the first was held in 1949; the congresses became especially popular and well attended beginning with the fifth, which was held in Moscow in 1961). In the USSR, the All-Union Biochemical Society, with numerous sections in the republics and cities, was organized in 1958. It has approximately 6,500 members. Actually, the number of biochemists in the USSR is much greater.
The quantity of periodical literature in which biochemical work is published is very great and continues to increase every year. Among the foreign and international journals, the best known are Journal of Biological Chemistry (Baltimore, 1905–), Biochemistry (Washington, D.C., 1964–), Archives of Biochemistry and Biophysics (New York, 1942–), Biochemical Journal (London, 1906–), Phytochemistry (Oxford-New York, 1962–), Molecular Biology (international journal published in England), Bulletin de la Société de Chimie Biologique (Paris, 1914–), Enzymologia (The Hague, 1936–), Giornale di Biochimica (Rome, 1955–), Acta Biologica et Medica Germanica (Leipzig, 1959–), Hoppe Seyler’s Zeitschrift für physiologische Chemie (Berlin, 1877–), and Journal of Biochemistry (Tokyo, 1922–). Popular yearbooks include Annual Review of Biochemistry (Stanford, 1932–), Advances in Enzymology and Related Subjects of Biochemistry (New York, 1945–), Advances in Protein Chemistry (New York, 1945–), Advances in Enzyme Regulation (Oxford, 1963–), and Advances in Molecular Biology. In the USSR, experimental work in biochemistry is published in the journals Biokhimiia (Moscow, 1936–), Zhurnal evoliutsionnoi biokhimii i fiziologii (Moscow, 1965–), Molekuliarnaia biologiia (Moscow, 1967–), Voprosy meditsinskoi khimii (Moscow, 1955–), Ukrainskii biokhimicheskii zhurnal (Kiev, 1926–), Prikladnaia biokhimiia i mikrobiologiia (Moscow, 1965–), Doklady AN SSSR (Moscow, 1933–), Biulleten’ eksperimental’noi biologii i meditsiny (Moscow, 1936–), Izvestiia AN SSSR: Seriia biologii i meditsiny (Moscow, 1936–), Izvestiia AN SSSR: Seriia khimicheskaia (Moscow, 1936–), and Nauchnye doklady vysshei shkoly: Seriia biologicheskie nauki (Moscow, 1958–).
General biochemical studies are published in the journal Uspekhi sovremennoi biologii (Moscow, 1932–), the yearbook Uspekhi biologicheskoi khimii (vols. 1–8, 1950–67) published by the All-Union Biochemical Society, the journals Uspekhi khimii (Moscow, 1932–) and Referativnyi zhurnal: Khimiia: Biologicheskaia khimiia (Moscow, 1955–), and the journal of the Mendeleev All-Union Society. Publications of biochemical institutes appear frequently.
Makeev, I. A., V. S. Gulevich, and L. M. Broude. Kurs biologicheskoi khimii. Moscow, 1947.
Kretovich, V. L. Osnovy biokhimii rastenii, 4th ed. Moscow, 1964.
Zbarskii, B. I., I.I. Ivanov, and S. R. Mardashev. Biologicheskaia khimia, 4th ed. Moscow, 1965.
Ferdman, D. L. Biokhimiia, 3rd ed. Moscow, 1966.
Prianishnikov, D. I zbr. soch., vol. 1. Moscow, 1951. Pages 5–19.
Gulevich, V. S. Izbrannye trudy. Moscow, 1954. Pages 5–21.
Parnas, Ia. O. Izbrannye trudy. Moscow, 1960. Pages 5–10.
Tolkachevskaia, N. F. Razvitie biokhimii zhivotnykh. Moscow, 1963.
Giua, M. Istoriia khimii. Moscow, 1966. (Translated from Italian.)
Razvitie biologii ν SSSR. Moscow, 1967.
Kretovich, V. L. Vvedenie ν enzimologiiu. Moscow, 1967.
Biokhimiia rastenii. Moscow, 1968. (Translated from English.)
Lieben, F. Geschichte der physiologischen Chemie. Leipzig-Vienna, 1935.
Engel’gardt, V. A. Nekotorye problemy sovremennoi biokhimii. Moscow, 1959.
Engel’gardt, V. A. Puti khimii ν poznanii iavlenii zhizni. Moscow, 1965.
Severin, S. E. Biokhimicheskie osnovy zhizni. Moscow, 1961.
Spirin, A. S. Informatsionnaia RNK i biosintez belkov. Moscow, 1962.
Skulachev, V. P. Sootnoshenie okisleniia i fosforilirovania ν dykhatel’noi tsepi. Moscow, 1962.
Fermenty. Edited by A. E. Braunshtein. Moscow, 1964.
Vladimirov, G. E., and N. S. PanteleeVa. Funktsional’naia biokhimiia. Leningrad, 1965.
Ingram, V. Biosintez makromolekul. Moscow, 1966. (Translated from English.)
Racker, E. Bioenergeticheskie mekhanizmy. Moscow, 1967. (Translated from English.)
Spirin, A. S., and L. P. Gavrilova. Ribosoma. Moscow, 1968.
S. E. SEVERIN