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Biochemistry

BIOCHEMISTRY

BIOCHEMISTRY, the chemical investigation and explanation of biological processes. American biochemistry acquired its institutional base as a result of the medical reform movement during the Progressive Era and was characterized until World War II by its emphasis on applied research and close association with medicine. American biochemists have been involved in the testing of foods and drugs, the development of diagnostic tests and medical treatments, and the production of consumer goods ranging from synthetic fibers and biological detergents to vitamin supplements and the contraceptive pill. Since the 1970s, biochemists have been actively engaged in biotechnological enterprises.

Biochemistry's antecedents lie in nineteenth-century Europe, where the rise of organic chemistry and experimental physiology generated much investigation into the chemical constituents of living organisms and the chemical changes associated with physiological functions. The many American scientists who trained in European laboratories imported these practices into the United States, where research in animal chemistry, agricultural chemistry, medical chemistry, and physiological chemistry gained a firm foothold in agricultural research stations, hospitals, colleges, and universities.

In the early 1900s, investigators in Europe and America sought to unite the diverse fields dealing with the chemistry of life under name of "biochemistry" or "biological chemistry" (then the preferred term in the United States). Among the first journals expressing this aim was the Journal of Biological Chemistry, founded in the United States in 1905. The American Society of Biological Chemists was constituted in 1906. In the same decade, many American medical schools, newly under university control, began to teach biochemistry as part of a nationwide reorganization of preclinical education. By 1920, most American medical schools had established departments of biochemistry where research had a predominantly clinical orientation.

Early American biochemists led in the development of new analytical methods for determining chemicals in the body that were used to diagnose specific diseases and monitor physiological states. Otto Folin at Harvard, Donald D. Van Slyke at the Rockefeller Institute Hospital in New York, and Stanley Benedict at Cornell acquired international renown. The widespread use of techniques they developed led simultaneously to redefinitions and reclassifications of diseases in chemical terms.

A second prominent stream of American biochemistry, that of nutritional investigation, built on established strengths in agricultural research, especially at experimental stations in Connecticut and Wisconsin. Recognition of the importance for health of vitamins stimulated much American research into the distribution of vitamins in foods, their chemical properties, and their role in metabolism. Diseases identified as resulting from vitamin deficiencies in the diet, such as rickets, scurvy, and pellagra, were cured and prevented by specific dietary changes. Commercially produced vitamin preparations and vitamin-fortified foods were widely promoted among the public from the 1920s and became an important source of profit for the American food and pharmaceutical industries.

In the 1930s, some American centers began to develop biochemistry as a broad, fundamental biological science, after the model of leading German, English, and Scandinavian schools. A similar vision was promoted by Warren Weaver, who, as manager of its Natural Sciences Division, turned the Rockefeller Foundation into the major international funding body for basic research in bio-chemistry and biophysics. In this decade, the biochemistry department at Columbia University in New York, headed by Hans T. Clarke, became the largest and most influential American school of basic biochemical research.

Clarke gave place in his department to an exceptionally high number of biochemists who had escaped national socialist regimes in Europe and who brought their distinctive research styles with them. Among them was Rudolf Schoenheimer, who, at Columbia, was responsible for a milestone in twentieth-century biochemistry: he introduced the use of isotopes as labels that allow biochemists to follow in detail how, and at what rate, specific molecules undergo change in metabolic reactions. His re-search with David Rittenberg and Sarah Ratner not only heralded the use of what has since become an indispensable tool in the life sciences but showed that all cell constituents are in constant flux: molecules are continuously being broken down and rebuilt from the foods organismsingest.

During World War II, biochemists participated in the war effort in major ways. For example, American biochemists were involved in the large-scale production of penicillin, other antibacterial drugs, and blood fractionation products for use in transfusion. These war-related projects involved complex translations between basic and applied research, managed through close collaborations between scientists, government, and industry. The blood fractionation project, organized by Edwin Cohn of the physical chemistry department at Harvard, was one of the wartime successes that stimulated a massive expansion of public funding for basic biochemical research in postwar America.

One manifestation of this new focus was the foundation of institutes dedicated to basic biochemistry, the first being the Enzyme Institute at the University of Wisconsin, opened in 1950. By the 1960s, fundamental biochemical research was firmly entrenched institutionally, and American biochemists were making ever more inter-nationally renowned contributions to all areas of bio-chemistry. Indicative of this trend is the rapid increase in Nobel laureates among American biochemists.

Between 1901 and 1950, only three Nobel Prizes were awarded for American biochemical research: the 1946 chemistry prize awarded to James B. Sumner, John H. Northrop, and Wendell M. Stanley for work on enzymes and virus proteins; and two prizes in physiology or medicine (shared with others abroad), awarded to Edward A. Doisy in 1943 for work on vitamin K, and to Carl F. Cori and Gerty Radnitz Cori in 1947 for work on glycogen metabolism. (Gerty Cori was the third woman, and the first woman biochemist, to win a Nobel Prize.) In the second half of the twentieth century, by contrast, approximately forty Nobel Prizes were awarded for American research with a biochemical dimension, to some seventy American laureates.

In this later period, biochemistry became increasingly intertwined with molecular biology and cell biology, partly through the development of new chemical, physical, and morphological techniques used in all three fields and through much traffic of biochemists across the boundaries between them. For biochemistry, these new developments made it possible to locate particular biochemical reactions in specific structures of the cell. Moreover, its institutional strength and practical flexibility enabled bio-chemistry to withstand challenges to its status as a fundamental science of life when these were issued in the 1950s and 1960s by molecular biologists seeking autonomy for their own science. In practice, there has been continuous overlap, and in 1987 the American Society of Biological Chemists renamed itself the American Society for Biochemistry and Molecular Biology.

BIBLIOGRAPHY

Apple, Rima D. Vitamania: Vitamins in American Culture. New Brunswick: Rutgers University Press, 1996.

Bud, Robert. The Uses of Life: A History of Biotechnology. New York: Cambridge University Press, 1993.

De Chadarevian, Soraya, and Harmke Kamminga, eds. Molecularizing Biology and Medicine: New Practices and Alliances, 1910s–1970s. Amsterdam: Harwood Academic Publishers, 1998.

Kohler, Robert E. From Medical Chemistry to Biochemistry: The Making of a Biomedical Discipline. Cambridge, U.K.: Cambridge University Press, 1982.

HarmkeKamminga

See alsoChemistry ; Medical Research ; Microbiology ; Molecular Biology ; Nutrition and Vitamins .

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Biochemistry

Biochemistry

Biochemistry seeks to describe the structure, organization, and functions of living matter in molecular terms. Essentially two factors have contributed to the excitement in the field today and have enhanced the impact of research and advances in biochemistry on other life sciences. First, it is now generally accepted that the physical elements of living matter obey the same fundamental laws that govern all matter, both living and non-living. Therefore the full potential of modern chemical and physical theory can be brought in to solve certain biological problems. Secondly, incredibly powerful new research techniques, notably those developing from the fields of biophysics and molecular biology , are permitting scientists to ask questions about the basic process of life that could not have been imagined even a few years ago.

Biochemistry now lies at the heart of a revolution in the biological sciences and it is nowhere better illustrated than in the remarkable number of Nobel Prizes in Chemistry or Medicine and Physiology that have been won by biochemists in recent years. A typical example is the award of the 1988 Nobel Prize for Medicine and Physiology, to Gertrude Elion and George Hitchings of the United States and Sir James Black of Great Britain for their leadership in inventing new drugs. Elion and Hitchings developed chemical analogs of nucleic acids and vitamins which are now being used to treat leukemia, bacterial infections, malaria , gout, herpes virus infections and AIDS . Black developed beta-blockers that are now used to reduce the risk of heart attack and to treat diseases such as asthma. These drugs were designed and not discovered through random organic synthesis. Developments in knowledge within certain key areas of biochemistry, such as protein structure and function, nucleic acid synthesis, enzyme mechanisms, receptors and metabolic control, vitamins, and coenzymes all contributed to enable such progress to be made.

Two more recent Nobel Prizes give further evidence for the breadth of the impact of biochemistry. In 1997, the Chemistry Prize was shared by three scientists: the American Paul Boyer and the British J. Walker for their discovery of the "rotary engine" that generates the energy-carrying compound ATP, and the Danish J. Skou, for his studies of the "pump" that drives sodium and potassium across membranes. In the same year, the Prize in Medicine and Physiology went to Stanley Prusiner , for his studies on the prion, the agent thought to be responsible for "mad cow disease" and several similar human conditions.

Biochemistry draws on its major themes from many disciplines. For example from organic chemistry, which describes the properties of biomolecules; from biophysics, which applies the techniques of physics to study the structures of biomolecules; from medical research, which increasingly seeks to understand disease states in molecular terms and also from nutrition, microbiology, physiology, cell biology and genetics. Biochemistry draws strength from all of these disciplines but is also a distinct discipline, with its own identity. It is distinctive in its emphasis on the structures and relations of biomolecules, particularly enzymes and biological catalysis, also on the elucidation of metabolic pathways and their control and on the principle that life processes can, at least on the physical level, be understood through the laws of chemistry. It has its origins as a distinct field of study in the early nineteenth century, with the pioneering work of Freidrich Wöhler. Prior to Wöhler's time it was believed that the substance of living matter was somehow quantitatively different from that of nonliving matter and did not behave according to the known laws of physics and chemistry. In 1828 Wöhler showed that urea, a substance of biological origin excreted by humans and many animals as a product of nitrogen metabolism , could be synthesized in the laboratory from the inorganic compound ammonium cyanate. As Wöhler phrased it in a letter to a colleague, "I must tell you that I can prepare urea without requiring a kidney or an animal, either man or dog." This was a shocking statement at the time, for it breached the presumed barrier between the living and the nonliving. Later, in 1897, two German brothers, Eduard and Hans Buchner, found that extracts from broken and thoroughly dead cells from yeast , could nevertheless carry out the entire process of fermentation of sugar into ethanol. This discovery opened the door to analysis of biochemical reactions and processes in vitro (Latin "in glass"), meaning in the test tube rather than in vivo, in living matter. In succeeding decades many other metabolic reactions and reaction pathways were reproduced in vitro, allowing identification of reactants and products and of enzymes, or biological catalysts, that promoted each biochemical reaction.

Until 1926, the structures of enzymes (or "ferments") were thought to be far too complex to be described in chemical terms. But in 1926, J.B. Sumner showed that the protein urease, an enzyme from jack beans, could be crystallized like other organic compounds. Although proteins have large and complex structures, they are also organic compounds and their physical structures can be determined by chemical methods.

Today, the study of biochemistry can be broadly divided into three principal areas: (1) the structural chemistry of the components of living matter and the relationships of biological function to chemical structure; (2) metabolism, the totality of chemical reactions that occur in living matter; and (3) the chemistry of processes and substances that store and transmit biological information. The third area is also the province of molecular genetics , a field that seeks to understand heredity and the expression of genetic information in molecular terms.

Biochemistry is having a profound influence in the field of medicine. The molecular mechanisms of many diseases, such as sickle cell anemia and numerous errors of metabolism, have been elucidated. Assays of enzyme activity are today indispensable in clinical diagnosis. To cite just one example, liver disease is now routinely diagnosed and monitored by measurements of blood levels of enzymes called transaminases and of a hemoglobin breakdown product called bilirubin. DNA probes are coming into play in diagnosis of genetic disorders, infectious diseases and cancers. Genetically engineered strains of bacteria containing recombinant DNA are producing valuable proteins such as insulin and growth hormone. Furthermore, biochemistry is a basis for the rational design of new drugs. Also the rapid development of powerful biochemical concepts and techniques in recent years has enabled investigators to tackle some of the most challenging and fundamental problems in medicine and physiology. For example in embryology, the mechanisms by which the fertilized embryo gives rise to cells as different as muscle, brain and liver are being intensively investigated. Also, in anatomy, the question of how cells find each other in order to form a complex organ, such as the liver or brain, are being tackled in biochemical terms. The impact of biochemistry is being felt in many areas of human life through this kind of research, and the discoveries are fuelling the growth of the life sciences as a whole.

See also Antibody-antigen, biochemical and molecular reactions; Biochemical analysis techniques; Biogeochemical cycles; Bioremediation; Biotechnology; Immunochemistry; Immunological analysis techniques; Miller-Urey experiment; Nitrogen cycle in microorganisms; Photosynthesis

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biochemistry

biochemistry The science of biochemistry, nowadays regarded as one of the fundamental pillars upon which the study of medicine rests, is something of a newcomer. It has its origins almost equally in chemistry and physiology, and indeed what we would today call biochemistry was commonly referred to as physiological chemistry a hundred years ago. Looking further back we can trace early ideas about the make-up of living things to the birth of organic chemistry, the scope of which seems originally to have been a good deal wider than would be admitted today. In 1806 Berzelius referred to organic chemistry as ‘the part of physiology which describes the composition of living bodies, and the chemical processes which occur in them. In the early nineteenth century there was a good deal of debate as to whether the chemical substances found in living things were fundamentally different in character from the ‘inorganic’ constituents of inanimate matter, and the issue was only resolved (in favour of no difference) with the chemical synthesis of urea by Wöhler in 1828 and by subsequent syntheses of molecules hitherto only associated with living organisms. Thereafter organic chemistry became confined to the study of carbon compounds, and knowledge of the transformations undergone by such compounds in the course of metabolism was left to be re-born as biochemistry decades later. A major influence in that re-birth was the concept of catalysis and the realization that catalysts must play a vital part in living processes. Here the studies of Pasteur and his contemporaries in the mid nineteenth century played an indispensable part, and led to the broad unifying concept that the nature of life processes must be very similar in disparate organisms, including man, and that catalytic enzymes (the word literally means ‘in yeast’) are responsible for directing and controlling chemical transformations in the living cell.

Given the acceptance of the concept of oxidation, and the demise of the phlogiston theory, thanks to the work of Lavoisier in the late 1700s, it was natural that the early study of metabolism should be preoccupied with understanding the processes of respiration, breakdown of sugars, and energy generation. There was also much interest in nutrition and the chemical processes underlying the digestion of food. The identification of enzymes as proteins arose naturally from these efforts and spawned the science of enzymology, which remains a major division of biochemistry to the present day. The question of how enzymes work engaged the attention of many of the finest biochemical brains in the 1990s and will continue to do so for the foreseeable future. Moreover, the day is not far away when enzymologists will astonish us all by creating more or less de novo enzymes endowed with hitherto-unknown catalytic properties. Already ‘catalytic antibodies’ have been described, that bind small molecules with exquisite specificity, producing chemical change, and as knowledge of fundamental mechanisms of catalysis emerges from the efforts of physical organic chemists, the practical applications of that knowledge will not be far behind.

It was with the arrival of the twentieth century that biochemistry came of age, so to speak, and made such a major impact on medicine that it was recognized as a formidable science indispensable to the understanding of the human body. Those were the days of vitamin and hormone research. The pioneering work of Sir Frederick Gowland Hopkins (1861–1947) and his colleagues, which led to the discovery of vitamins, had a lasting influence on generations of biochemists and underpinned the unravelling of intermediary metabolism. The isolation, identification, and eventual production of hormones in sufficient quantity for therapeutic use likewise illuminated some of the most perplexing medical problems, and transformed endocrinology into an important branch of clinical science.

Biochemistry has long boasted of its roots in exact physical sciences and has never been afraid to divert the attentions of practitioners of those sciences to the study of life. By that route some of the most spectacular advances of knowledge in the twentieth century have been achieved, perhaps none more so than the birth of the enfant terrible, molecular biology, which nowadays dominates the subject. Molecular biology, rooted in structural studies on proteins and nucleic acids, owes much to the contributions of far-sighted crystallographers and geneticists (aided and abetted by a cohort of physicists and even mathematicians) who built upon the bed-rock of biochemistry to produce a veritable revolution in biology that is still evolving apace. It is sometimes hard to imagine how abstract the concept of a gene was prior to the discovery of the structure of DNA by Watson and Crick in 1953, since nowadays the precise identification of genes and expectations of their manipulation (for good or ill) can be read about in newspapers intended for the man in the street. Biochemistry is no longer the academic tool of medical researchers but, having embraced its sister disciplines in the physical as well as biological sciences, has taken on new meaning as the huge promise of biotechnology looms before us.

Never has it been more evident how the pace of scientific discovery is driven by technical advances in experimentation, the invention of new techniques, and the application of ideas imported from cognate disciplines. The twin sciences of molecular and cell biology have adapted the foundations laid by the painstaking ‘bucket’ experiments of the early biochemists to illuminate the marvels and mysteries of molecules and cells in a fashion which can only be described as spectacular. Even philosophers and theologians can no longer ignore the prospects of bio-revolution introduced into our daily lives: genetically engineered foodstuffs; super-athletes; new approaches to treating infertility; eradication of diseases. How many more triumphs (or horrors) attributable to the application of biochemically-based technology await us? And how are we going to cope with them?

M. J. Waring

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biochemistry

biochemistry The study of the chemistry of living organisms, especially the structure and function of their chemical components (principally proteins, carbohydrates, lipids, and nucleic acids). Biochemistry has advanced rapidly with the development, from the mid-20th century, of such techniques as chromatography, spectroscopy, X-ray diffraction, radioisotopic labelling, and electron microscopy. Using these techniques to separate and analyse biologically important molecules, the steps of the metabolic pathways in which they are involved (e.g. glycolysis and the Krebs cycle) have been determined. This has provided some knowledge of how organisms obtain and store energy, how they manufacture and degrade their biomolecules, how they sense and respond to their environment, and how all this information is carried and expressed by their genetic material. Biochemistry forms an important part of many other disciplines, especially physiology, nutrition, and genetics, and its discoveries have made a profound impact in medicine, agriculture, industry, and many other areas of human activity. See Chronology.

BIOCHEMISTRY

1833

French chemist Anselme Payen (1795–1871) discovers diastase (the first enzyme to be discovered).

1836

Theodor Schwann discovers the digestive enzyme pepsin.

c.1860

Louis Pasteur demonstrates fermentation is caused by ‘ferments’ in yeasts and bacteria.

1869

German biochemist Johann Friedrich Miescher (1844–95) discovers nucleic acid.

1877

Pasteur's ‘ferments’ are designated as enzymes.

1890

German chemist Emil Fischer (1852–1919) proposes the ‘lock-and-key’ mechanism to explain enzyme action.

1901

Japanese chemist Jokichi Takamine (1854–1922) isolates adrenaline (the first hormone to be isolated).

1903

German biologist Eduard Buchner (1860–1917) discovers the enzyme zymase (causing fermentation).

1904

British biologist Arthur Harden (1865–1940) discovers coenzymes.

1909

Russian-born US biochemist Phoebus Levene (1869–1940) identifies ribose in RNA.

1921

Canadian physiologist Frederick Banting (1891–1941) and US physiologist Charles Best (1899–1978) isolate insulin.

1922

Alexander Fleming discovers the enzyme lysozyme.

1925

Russian-born British biologist David Keilin (1887–1963) discovers cytochrome.

1926

US biochemist James Sumner (1877–1955) crystallizes urease (the first enzyme to be isolated).

1929

German chemist Hans Fischer (1881–1945) determines the structure of haem (in haemoglobin).

K. Lohman isolates ATP from muscle.

1930

US biochemist John Northrop (1891–1987) isolates the enzyme pepsin.

1932

Swedish biochemist Hugo Theorell (1903–82) isolates the muscle protein myoglobin.

1937

Hans Krebs discovers the Krebs cycle.

1940

German-born US biochemist Fritz Lipmann (1899–1986) proposes that ATP is the carrier of chemical energy in many cells.

1943

US biochemist Britton Chance (1913– ) discovers how enzymes work (by forming an enzyme–substrate complex).

1952

US biologist Alfred Hershey (1908– ) proves that DNA carries genetic information.

1953

Francis Crick and James Watson discover the structure of DNA.

1955

Frederick Sanger discovers the amino acid sequence of insulin.

1956

US biochemist Arthur Kornberg (1918– ) discovers DNA polymerase.

US molecular biologist Paul Berg (1926– ) identifies the nucleic acid later known as transfer RNA.

1957

British biologist Alick Isaacs (1921–67) discovers interferon.

1959

Austrian-born British biochemist Max Perutz (1914– ) determines the structure of haemoglobin.

1960

South African-born British molecular biologist Sydney Brenner (1927– ) and French biochemist François Jacob (1920– ) discover messenger RNA.

1961

British biochemist Peter Mitchell (1920–92) proposes the chemiosmotic theory.

Brenner and Crick discover that the genetic code consists of a series of base triplets.

1969

US biochemist Gerald Edelman (1929– ) discovers the amino acid sequence of immunoglobulin G.

1970

US virologists Howard Temin (1934–94) and David Baltimore (1938– ) discover the enzyme reverse transcriptase.

1970

US molecular biologist Hamilton Smith (1931– ) discovers restriction enzymes.

1973

US biochemists Stanley Cohen (1935– ) and Herbert Boyer (1936– ) use restriction enzymes to produce recombinant DNA.

1977

Sanger determines the complete base sequence of DNA in bacteriophage φX174.

1985

British biochemist Alec Jeffreys (1950– ) devises DNA fingerprinting.


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Biochemistry

Biochemistry

Biochemistry is the science dealing with the chemical nature of the bodily processes that occur in all living things. It is the study of how plants, animals, and microbes function at the level of molecules.

Biochemists study the structure and properties of chemical compounds in the cells of living organisms and their role in regulating the chemical processes (collectively called metabolism) that are necessary to life. These chemical processes include transforming simple substances from food into more complex compounds for use by the body, or breaking down complex compounds in food to produce energy. For example, amino acids obtained from food combine to form protein molecules, which are used for cell growth and tissue repair. One very important type of protein are enzymes, which cause chemical reactions in the body to proceed at a faster rate.

Complex compounds in food, such as proteins, fats, and carbohydrates, are broken down into smaller molecules in the body to produce energy. Energy that is not needed immediately is stored for later use.

Words to Know

DNA (deoxyribonucleic acid): A nucleic acid molecule (an organic molecule made of alternating sugar and phosphate groups connected to nitrogen-rich bases) containing genetic information and located in the nucleus of cells.

Gene: A section of a DNA molecule that carries instructions for the formation, functioning, and transmission of specific traits from one generation to another.

Metabolism: The sum of all the chemical processes that take place in the cells of a living organism.

Proteins: Large molecules that are essential to the structure and functioning of all living cells.

Biochemistry also involves the study of the chemical means by which genes influence heredity. (A gene is a molecule of DNA, or deoxyribonucleic acid, which is found in the nucleus of cells. Genes are responsible for carrying physical characteristics from parents to offspring.) A gene can be seen as a sequence of DNA that is coded for a specific protein molecule. These proteins determine specific physical traits (such as hair color, body shape, and height), body chemistry (such as blood type and metabolic functions), and some aspects of behavior and intelligence. Biochemists study the molecular basis of how genes are activated to make specific protein molecules.

[See also Amino acid; Carbohydrate; Chromosome; Enzyme; Hormones; Lipids; Metabolism; Molecular biology; Nucleic acid; Photosynthesis; Protein ]

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biochemistry

bi·o·chem·is·try / ˌbīōˈkeməstrē/ • n. the branch of science concerned with the chemical and physicochemical processes that occur within living organisms. ∎  processes of this kind: abnormal brain biochemistry. DERIVATIVES: bi·o·chem·i·cal / -ˈkemikəl/ adj. bi·o·chem·i·cal·ly adv. bi·o·chem·ist / -ˈkemist/ n.

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biochemistry

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