Biochemistry

Is a Broad Scientific Discipline

Biochemistry is the study of the structure, composition, and chemical reactions of substances in living systems. Biochemistry emerged as a separate discipline when scientists combined biology with organic, inorganic, or physical chemistry and began to study such topics as how living things obtain energy from food, the chemical basis of heredity, and what fundamental changes occur in disease. Biochemistry includes the sciences of molecular biology; immunochemistry; neurochemistry; and bioinorganic, bioorganic, and biophysical chemistry.

Has a Wide Range of Applications

Biochemistry is applied to medicine, dentistry, and veterinary medicine. In food science, biochemists research ways to develop abundant and inexpensive sources of nutritious foods, determine the chemical composition of foods, develop methods to extract nutrients from waste products, or invent ways to prolong the shelf life food products. In agriculture, biochemists study the interaction of herbicides with plants. They examine the structureactivity relationships of compounds, determine their ability to inhibit growth, and evaluate the toxicological effects on surrounding life. Biochemistry spills over into pharmacology, physiology, microbiology, and clinical chemistry. In these areas, a biochemist may investigate the mechanism of a drug action; engage in viral research; conduct research pertaining to organ function; or use chemical concepts, procedures, and techniques to study the diagnosis and therapy of disease and the assessment of health. Work in the field of biochemistry is often related to toxicology. Rogene Henderson, senior scientist and supervisor of the Biochemical Toxicology Group at Lovelace Respiratory Research Institute, does research to understand ways in which organic compounds in the body are changed by enzymes into toxic metabolites. Henderson focuses on determining the health effects of inhaled pollutants. She develops chemical analytical techniques to detect pollutants and their metabolites in body tissues and fluids, uses mathematics to describe the relationships between the air and body concentrations of these chemicals or their metabolites, and determines how these concentrations change with time.

Source: http://portal.acs.org

INTRODUCTION

Biochemistry is the study of the chemical processes and transformations in living organisms. Since life forms alive today are hypothesized by some to have descended from the same common ancestor, they would naturally have similar biochemistries, even for matters that seem to be essentially arbitrary, such as handedness of various biomolecules. It is unknown whether alternative biochemistries are possible or practical.Biochemistry deals with the structure and function of cellular components, such as proteins, carbohydrates, lipids, nucleic acids, and other biomolecules. Chemical biology aims to answer many questions arising from biochemistry by using tools developed within synthetic chemistry. Originally, it was generally believed that life was not subject to the laws of science the way non-life was. It was thought that only living beings could produce the molecules of life (from other, previously existing biomolecules). Then, in 1828, Friedrich Whler published a paper about the synthesis of urea, proving that organic compounds can be created artificially. The dawn of biochemistry may have been the discovery of the first enzyme, diastase (today called amylase), in 1833 by Anselme Payen. Eduard Buchner contributed the first demonstration of a complex biochemical process outside of a cell in 1896: alcoholic fermentation in cell extracts of yeast. Although the term biochemistry seems to have been first used in 1881, it is generally accepted that the formal coinage of biochemistry occurred in 1903 by Carl Neuber, a German chemist. Since then, biochemistry has advanced, especially since the mid-20th century, with the development of new techniques such as chromatography, X-ray diffraction, NMR spectroscopy, radioisotopic labelling, electron microscopy and molecular dynamics simulations. These techniques allowed for the discovery and detailed analysis of many molecules and metabolic pathways of the cell, such as glycolysis and the Krebs cycle (citric acid cycle).Today, the findings of biochemistry are used in many areas, from genetics to molecular biology and fromagriculture to medicine.

BIOCHEMISTRY Derivation Biochemistry is the combination of two words-one is Bio and another is Chemistry. Bio means life and Chemistry means the science of chemicals. So, literally we can say that biochemistry is the science of chemicals of life. Definition There are many definitions of biochemistry are existed. Among them the most important definitions are given below: Actually, biochemistry is science concerned with the various biomolecules such as carbohydrates, proteins, lipids etc. those occur in living cells and organisms with their chemical reaction. It is the science concerned with the chemical constituents of living cells and with the chemical constituents of living cells and with the reactions and processes that they undergo. Biochemistry is concerned with structural chemistry. It seeks to determine the structures of molecules found in living systems in order to understand structure-function relationships. Biochemistry is concerned with chemical change; this is reflected in the study of metabolic pathways. Biochemistry is concerned with information which has accumulated through evolution and is preserved in DNA (or sometimes RNA). These nucleic acid sequences code for amino acid sequences, which result in folded proteins. These proteins are often catalysts (enzymes) and some of them are regulated (able to sense the chemical state inside the cell and, in some cases, the outside).Although there are a vast number of different biomolecules, many are complex and large molecules (called polymers) that are composed of similar repeating subunits (called monomers). Each class of polymeric biomolecule has a different set of subunit types. For example, a protein is a polymer made up of many amino acids. Biochemistry studies the chemical properties of important biological molecules, like proteins, in particular the chemistry of enzymecatalyzed reactions (enzymes are a type of protein).The biochemistry of cell metabolism and the endocrine system has been extensively described. Other areas of biochemistry include the genetic code (DNA, RNA), protein synthesis, cell membranetransport, and signal transduction.

FISH

BIOCHEMISTRY

The science concerned with the chemical constituents of living cells of fish and relevant reactions and processes that they undergo. It is the applied branch of biochemistry which deals with different biological and bimolecular reactions or metabolism of fish. IMPORTANCE OF FISH BIOCHEMISTRY

Fish Biochemistry deals with the followings of fishes:

The chemistry of tissues and foods. The chemistry of digestion and absorption. The chemistry of respiration The chemistry of blood The chemistry of cell membrane and physical chemistry The chemistry of tissue metabolism The chemistry of glands of internal secretion The chemistry of excretion

The chemistry of tissues and foods Since the foods are largely derived from animals or plant tissue the study of the chemistry of one is identical with the other. The components of tissues and foods are carbohydrates, fats, proteins and nucleic acids. Carbohydrates provide a greater part of the energy needs to the body. Improper utilization of glucose leads to the development of the diseases diabetes mellitus. Lipids provide a part of the energy needs of the body. Essential fatty acids are required maintaining normal health. These essential fatty are also the precursors of prostaglandins. Complex lipids occur as internal parts of nervous tissue. Proteins are necessary for growth and maintenance of positive nitrogen balance. Nucleic acids (DNA and RNA) of nucleus and cytoplasm respectably are involved in regulation of gene. The chemistry of digestion and absorption The food is chiefly composed of large molecules of starch, proteins and fats. These large molecules are digested into smaller molecules like glucose, amino acids, and fatty acids for absorption by the organic catalysts (the enzymes) present on the digestive juice. Along with their absorption, the entry of water, minerals, vitamins and other diffusible molecules of the food also takes place. The absence of one of the digestive enzymes leads to serious disorders.

The chemistry of respiration During respiration, oxygen is taken and diffuses into the blood across the membranes. It combines with the hemoglobin of red blood cells and in this form, it carried to the tissues where it is released for the oxidation of food to liberate energy. The carbon dioxide formed equal in volume to that of oxygen passes from the tissues to the blood stream and is exhaled being reacted by chemical combination.

The chemistry of blood The bloods carried foods to the tissues and waste products from them to the excretory organ. The hormones produced by various glands pass into the blood and through its circulation these hormones reach the specific tissues. The blood distributes heat from one part of the body to another and excerts cooling effect. The blood also distributes water and salts properly and maintains acid-base balance of the body. It contains substances that combat infection by microorganisms. The composition of blood is normally constant but it is dynamic. One of substances present in it increased or decreased causes different disease. The chemistry of cell membrane and physical chemistry Hormones, foods, waste products, and other necessary substances required for cells pass through the cell membrane. Some substances easily pass through the cell membrane. Some substances easily pass through the membranes but some other substances pass by other mechanisms. Normal permeability of cell membranes maintains normal physiological processes and abnormal permeability is associated with pathological conditions. The colloidal substances which do not diffuse through membranes exhibit donnan membrane equilibrium resulting in secretion and excretion of substances. The buffering system is most essential for maintaining pH of blood slightly alkaline for normal functioning of the body. The electrical potentials across cell membranes are of much significance. The ion exchange across the cell membrane maintains the cellular integrity. The pH of blood is altered from the normal value leads to complicated disorders.

HHHHHHH The chemistry of tissue metabolism

The oxidation of food stuff in tissues occurs by chemical processes with the liberation of energy and water. This is very complicated process in biochemistry. Several diseases occur in the disorder of metabolism of these food stuffs. The chemistry of glands of internal secretion The control through glands of internal excretion is barely dependent on the activities of hormones and nervous system. The hormone of one gland regulates the activity of another gland. Biological achievement is recorded by the biochemistry of the glands of internal secretion which is one of the most significant chapters. The improvement of this chapter has influenced the effective agents of treating diseases. Overproduction of hormones also leads to serious disorders. The chemistry of excretion The excretory organs-kidneys, lungs, gills in fishes, intestine and skin-remove decomposition products of tissues and foods in order to make the composition of the body fluids constant. The most important decomposition products are urea, uric acid and creatinine formed from proteins; carbon dioxide and water formed from carbohydrates, fats and proteins. The particular level of these decomposition products in compatible with health but much excess may lead to dysfunction and illness. The kidneys and the lungs chiefly perform the excretory function of the body. IMPORTANCE OF FISH BIOCHEMISTRY IN NATIONAL HEALTH Proper knowledge of fish biochemistry helps to prevent and protect several diseases. Fish body contains all the essential amino acids, fatty acids, poly and highly unsaturated (PUFA and HUFA) fatty acids at a higher amount. Fish body also contain higher amount of vitamins and minerals. Fish biochemistry plays an important role in our national health because it helps to know the followings: Fish as a source of vitamins and minerals Fishes are the most important sources of nutrition (vitamins and minerals). So, fish should be supplied at a higher amount to human to full-fill the nutritional requirement. Nutritional values of some fishes are given in the following chart:

Table- 1: Nutritional values of different fishes. Fish species Mola Chela Dankina Chanda Puti Katchki Ilish Silver carp Rui Tilapia Vitamin- A (mg/100 gm) 1960 937 1457 341 37 93 69 17 27 19 (Matshya pakkha- 2005) Calcium(mg/100 gm) 1071 1260 590 1162 1059 126 268 317 Iron(mg/ 100 gm) 7 1.96 3 5

Table- 2: Nutritional value and fatty acids of some fishes. Fish Species Protein Sar punti Mola Punti Dankina Koi Bata 16.5 18.1 14.6 14.8 14.3 mg per 100 gm body weight Calcium 220 1071 1059 590 410 79 Phosphorus 120 340 390 200 Iron .54 7 1.96 135 1.09 Lipid 9.5 2.4 14.3 8.8 2.48

Foli Taki Bele Shing

19.8 19.4 14.5 22.8

590 610 370 670

450 53 330 650

169 130 104 226

1 0.6 0.6 0.6

(Matshya pakkha- 2005) Importance of fish oil and lipid Fish oil contain higher amount of HUFA, PUFA, Omega- 3 and omega- 6 fatty acids. Fish oil reduces down the cholesterol level of blood and protect from heart failure. Recently, a researcher of Norway has discovered that fatty fish could have the power to destroy cancer cell. Importance in Artherities Secretion of prostoglandlin hormone causes the Autoimmune artherities. Aspirin is used as medicine for this disease which stops the secretion of prostoglandlin hormone. Omega- 3 and omega- 6 fatty acids do the same work as the aspirin. As the fish lipid contain higher amount of omega-3 and 6 fatty acids, so fish lipid can reduce the arthritic pain. Importance in Diabetes Fish lipid increase the secretion of insulin and also increase the activity of insulin. So, fish lipid can reduce the level of diabetes. Importance in brain development Lipid constitutes about 60% of our total brain. So, lipid plays an important role in brain development. Fish lipid plays a vital role in this case. As micronutrients Fish is an efficient source of vitamins and minerals. Calcium helps in the function and development of muscle, teeth and bone. Phosphorus helps in energy production in terms of ATP and helps in the function

SCOPE

OF

FISH

BIOCHEMISTRY

Biochemistry in its broad aspects is the most comprehensive of all the branches of chemistry. It includes inorganic, organic and physical chemical and it is related with all of living things both plant and animal. Biochemistry has various relationships with fish and its metabolism. As a processor A fish biochemist can work as a processor in a fish processing industry. The processor knows the nature of the raw materials before he can correctly apply the technique of chilling, freezing, smoking or canning. The processor also knows the proximate composition of fish (amount of carbohydrate, protein, vitamins, minerals and extractives etc.) to make the best technique for processing and preservation. As for example, Hilsa cannot be dried without salt because it is a fatty fish. As a nutritionist A fish biochemist can work as a nutritionist. The nutritionists know the contribution that the fish can make to the diet and to health. They also measure the amount of protein, lipid, carbohydrate, vitamins, minerals, water, and extractives of fish body which will be beneficial or harmful for body. As a teacher A good fish biochemist can work as a teacher in different schools, colleges and universities. He can teach the students both from theoretical and practical aspects. He can provide information to the students about the different components of fish that are the index of fish spoilage. So, the students can learn better technique for fish processing, preservation etc. which is helpful for the development of fisheries sector. As a researcher and scientist The fish biochemists can work as researcher and scientist in national, governmental laboratories and in different NGOs. They can develop new technique for fish processing and preservation. They can also help to find out the suitable conditions for live fishes. In industry The fish biochemists can work in different industries. The fish biochemists know the amount of oil in the liver of some fishes like Cod. So, higher production of cod liver oil is possible in industries with the help of fish biochemists. In aquaculture

The fish biochemists can work in different hatcheries, fish firms and in different aquaculture projects. Fish biochemistry deals with the respiration, digestion, absorption, transport of gases and food particles through blood, anabolism, catabolism, metabolism of different food particles like protein, carbohydrate, lipid, vitamins and minerals etc. So, higher fish production is possible by the application of the knowledge of fish biochemistry which ensures successful aquaculture. Chemistry of food and nutrition Foods are largely derived from animal or plant tissue. Study of this in varies essential. These foods in taken or absorbed by bio-chemical process. This foods are mostly organic substance and classes of the more carbohydrate, fatty materials, protein, lipid etc. their function is related with bio-chemical process e.g. 1 gm protein 4.2 K Cal energy. 1 gm carbohydrate -4 K Cal energy. 1 gm lipid 9 K Cal energy. All of this energy is secreted biochemical Chemistry of digestion and absorption Much of fish food is composed of large molecule such as protein, carbohydrate, lipid, fat etc. this type of is digested or absorbed by biochemical process. E.g . Carbohydrate Glucose, Fructose. Protein Amino acid. Lipid Fatty acid. Chemistry of respiration Respiration is an obligatory property of living protoplasm of higher forms of life. Chemistry of blood The circulatory blood represents the transport system within and between the organs of the body. Blood carries food to the tissue. It also transports hormones and other substances biochemical.

Chemistry of metabolism Metabolism is the series of biochemical reaction in the living cell catalyzed by enzyme, co enzyme to convert the higher molecule into simpler forms within tissue cells by which protoplasm in synthesize or broken down and foods are utilized to supply energy for the living process. Cell metabolism Cell composed biochemically. Various types of reaction occur in the cell. Composition of cell depends on biochemistry. To learn about fish lipid For tissue culture Chemistry of medicine Artificial breeding of fish HISTORY OF BIOCHEMISTRY

The history of chemistry, and in particular of biochemistry, is a subject with a poorly defined structure. It lacks the general theories of physics, and even the major theories of evolution. To some extent this is true of all history, but general history brings with it a heavy ideological baggage, which the history of chemistry largely lacks. Thus, it belongs to the author of this history to impose his own structure on a rather amorphous subject: one has not the history so much as a history of biochemistry. Dr. Hunters guiding principle in erecting his structure is to focus on the historical origins of our understanding of the central mechanisms of transmission and expression of hereditary information. Dr. Hunters study includes early history, and he avers that: To prescientific societies it must have seemed obvious that there was a qualitative difference between life and non-life . However, all the evidence goes to show that early men saw nature as being of one kind, but for just the opposite reasons to nineteenth century materialism, which tended to see nature as purely mechanical. For prehistoric tribes, all nature was alive and peopled with gods; the stones and rocks, rivers and seas quite as much as plants and animals. The Milesians were the first Greek philosophers and for them too all nature was alive, or filled with Soul. During the later medieval period, and influenced particularly by Aristotles classification of the soul into four levelsmineral, vegetable, animal, and

humanscholasticism had reflected the hierarchical Roman church and stratified feudal society, and sought to mirror this in a fundamentally unchanging world, with fixed species and a short, biblical timescale. In geology the actual timescale slowly emerged from the rocks. Biology gradually became evolutionary, culminating in Darwins Origin of Species and Descent of Man. The ideological problem for biochemistry was to remove in all its aspects vitalism, or the idea that life depended on a special vital force, which ultimately descended from Aristotles theory of the soul. The idea of separate laws which governed the inanimate and the animate was threatened by the chemical revolution, in particular by Lavoisiers development of the analogy between combustion and respiration. Also, his law of the conservation of matter arose from a study of fermentation: Chemistry and biological processes were becoming intertwined. Lavoisiers theoretical work, which was part of the Enlightenment, owed much to the English chemists, including Priestley and Cavendish, and his Elements of Chemistry (1789) severed chemistrys remaining connections with its alchemical past. In the nineteenth century, chemistry in its biological aspects gradually achieved a consistently materialist approach. During the nineteenth century organic chemistry, founded on the enormous advances in inorganic chemistry, together with elucidation of the nature of the cell, laid the foundations for the development of biochemistry as a separate discipline. Two crucial developments as early as the 1830s were the discovery of isomerism, which gave the first hints of the complexity of organic molecules, and the identification of enzymes as catalysts. However, it was around the turn of the century that the behavior of enzymes really began to be elucidated, and with the establishment of the composition of simple proteins biochemistry developed in earnest. In the twentieth century, novel physical techniques, including electron microscopy and X-ray crystallography, made possible the detailed analysis of structure. The ultracentrifuge aided biochemistry. The pioneering crystallographers the Braggs were joined by the energetic John Desmond Bernal, and the great Cambridge group began to take shape. By the late 1930s we come to names whose work is still well known, including Max Perutz, who joined Bernal in Cambridge in 1936, Jacques Monod, and others. In 1937 Perutz showed X-ray pictures of hemoglobin to Lawrence Bragg, now Cavendish professor at Cambridge. Very gradually the giant biological molecules were coming to be understood as aperiodic polymers, culminating later in Erwin Schrdingers seminal book What Is Life (1944, Cambridge University Press). When World War Two began the subject was poised for major advances. The war led to a great range of technical developments, and when peace returned instrumentation advanced rapidly. Digital computers first aided

analysis, and later began to be used for direct control of instruments. Genes were soon shown to be composed of nucleic acid, but two central questions remained: How do genes reproduce? And how do they act? These problems are still being elucidated, but in a degree of detail that could scarcely have been imagined in the middle of the twentieth century. Determination of the genomes of yeast, C. elegans, and Drosophila, as well as the human genome, and now of an increasing range of organisms, is beginning to yield the rich harvest which was promised half a century ago, both in structural and evolutionary terms. In all, it is difficult to feel that Dr. Hunter has been entirely successful in carving out a coherent body of material or in creating a clear picture of the history of biochemistry. In particular, one could wish that he had kept a firmer grasp on chronology. However, he has made a pioneering attempt at analyzing an exceedingly complex and fascinating subject. Highlights of History Dat Discovery e 1770 Priestkly showed that oxygen is produced by plants and consumed by animals. Wohler synthesized the first organic compound, urea, from inorganic components. Jons Berzelius wrote a paper on chemical catalysis, used amylase as an example. Schleiden and Schwann proposed that all living things are composed of cells.

1773 Rouelle isolated urea from urine. 1828 1835 1838

1859 Charles Darwin published On the Origin of Species. 1860 Louis Pasteur recognized that fermation was catalyzed by enzymes, but he believed they are part of the essence of yeast. 1864 Hoppe-Seyler crystallized hemoglobin. 1865 1869 Gregor Mendel published his theory of genetics. Fredrick meischer discovered DNA in cell nuclei.

1893 Ostwald showed that enzymes are catalysts.

Eduard and Hans Buchner extracted materiel from yeast that catalyzed the conversion of glucose to alcohol. Eduard Buchner 1897 was awarded the 1907 Nobel Prize in Chemistry for his biochemical investigations and his discovery of non-cellular fermentation. 1898 Camillio Golgi described the Golgi apparatus. 1900 Gregor Mendels work on genetics was rediscovered. Knoop deduced degradation. the oxidation mechanisms for fatty acid

1905 1907

Fletcher and Hopkins showed that lactic acid is formed quantitatively from glucose during anaerobic muscle contraction. Warburg postulated a respiratory enzyme for the activation of oxygen. Michaelis and Menten developed a kinetic theory of enzyme action. Fritz Lipmann elucidated the role of ATP in energy metabolism.

1910 Morgan discovered sex-limited inheritance in Drosophila. 1912 1913 1914

1922 McCollum showed that lack of vitamin D causes rickets. 1926 James Sumner obtained crystalline demonstrated that it is a protein. 1926 1926 jack bean urease and

Jansen and Donath isolated vitamin B1 (thiamine) from rice polishings. Thomas Hunt Morgan wrote The Theory of the Gene. Svedberg invented the ultracentrifuge and used it to demonstrate the existence of macromolecules. Levene showed that nucleotides are the building blocks of nucleic acids. Warburg deduced the iron-prophyrin presence in the respiratory enzyme.

1926 1928

1928 Szent-Gyorgyi isolated ascorbic acid (Vitamin C). 1928

1929 1931 1932

Burr and Burr discovered that linoleic acid is an essential fatty acid for animals. Englehardt discovered respiration. that phosphorylation is coupled to

Warburg and Chiristian discovered the yellow enzyme, a flavoprotein. Embden and Meyrhof demonstrated the intermediates in the glycolytic pathway. Arnold Beckman developed the first pH meter.

1933 Krebs and Henseleit discovered the urea cycle. 1933 1934

1935 Stanley first crystallized a virus, tobacco mosaic virus. 1937 Hans Krebs discovered the citric acid cycle (TCA cycle). Warburg showed how ATP formation is coupled dehydrogenation of glyceraldehyde-3-phosphate. to the

1937 1938 1939 1939

Hill found that cell-free suspensions of chloroplasts yield oxygen when illuminated in the presence of an electron acceptor. C. Cori and G. Cori demonstrated the reversible action of glycogen phosphorylase. Lipman postulated the central role of ATP in the energy-transfer cycle.

1939 Szent-Gyorgyi discovered actin and the actin-myosin complex. 1941 George Beadle and Edward tatum proposed the one-gene, oneenzyme hypothesis. 1942 1943 Bloch and Rittenberg discovered that acetate is the precursor of cholesterol. Clance applied spectrophotometric methods to the study of enzyme-substrate interactions.

1943 Martin and Synge developed partition chromatography. 1944 Oswald Avery, Colin MacLeod, and Maclyn McCarthy used chemical methods to establish that DNA is the genetic material. 1947 Lipmann and Kaplin isolated and characterized coenzyme A.

1948 1948

Leloir discovered the role of uridine nucleotides in carbohydrate metabolism. Hogeboom, Schneider and Palade refined the centrifugation mthod for fractionation of cell parts. differ4ential

Kenedy and Lehninger discovered that the tricarboxylic acid cycle, 1948 fatty acid oxidation and oxidative phosphorylation all take place in mitrochondria. 1949 Christian deDuve discovered lysosomes. 1950 Edwin Chargaff published observation that A=T, G=C (Chargaffs rules). 1951 Lynen postulated the role of coenzyme A in fatty acid oxidation. 1952 Palade, Porter and Sjostrand perfected thin sectioning and fixation methods for electron microscopy of intracellular structures.

1952 Linus Pauling and Robert Corey proposed the a-helix and the bpleated sheet structures for proteins. 1952 Alfred Hershey and Martha Chase provide additional support for DNA as genetic material. 1952 1953 Zameenik and his colleagues developed the first cell-free systems for the study of protein synthesis. Woodward and Bloch postulated a cyclization scheme swualene, leading to cholesterol. for

1953 Fredrick Sanger determines the first amino acid sequence of a protein (insulin). 1953 1953 Hokin and Hokin showed that acetylcholine induces the rapid biosynthesis of phosphatidylinositol in pigeon pancreas. Hirecker, Dickens and Racker elucidated the 6-phosphoglucinte pathway of glucose catabolism.

1953 James Watson and Frances Crick and Wilkins determined the double-helix model of DNA. 1954 1955 Hugh Huxley proposed the sliding filament model for muscular contraction. Ochoa and Grunburg-Manago phosphorylase. discovered polynucleotide

1955

Kennedy and Weiss described the role of CTP in the biosynthesis of phosphatidylcholine. Umbarger reported that the end product isoleucine inhibits the first enzyme in its biosynthesis from threonine. Dorothy Crawfoot Hodgkin determined the structure of coenzyme B12. Ingram showed that normal and sickle-cell hemoglobin differ in a single amino acid residue.

1956 Kornberg discovered the first DNA polymerase. 1956 1956 1956

Anfinsen and White concluded that the three-dimensional 1956 conformation of proteins is specified by their amino acid sequence. 1956 Leloir determined the pathway to uridine diphosphate glucose. 1956 Earl Sutherland isolated cyclic AMP. Hoagland, Zameenik and determined its function. Weiss, Hurwitz polymerase. and Stephenson discovered isolated tRNA and RNA

1957 1957

Stevens

DNA-directed

1957 Matthew Meselson and Franklin Stahl carried out experiment to demonstrate semiconservative DNA replication. 1959 Wakil and Ganguly reported that intermediate in fatty acid biosynthesis. malonyl-CoA is a key

1960 John Kendrew and Max Pertuz obtained the first three dimensionalstructure of proteins (hemoglobin and myoglobin). 1960 Jerald Huritz and Samuel Weiss discovered RNA polymerase. 1961 1961 1961 Francois Jacob and Jaques Monod proposed the operon model of gene control. Jacob, Monod and Changeux proposed a theory of the function and action of allosteric enzymes. Mitchell postulated the chemiosmotic mechanism of oxidative phosphorylation. hypothesis for the

1961 Nirenberg and Matthaei reported that polyuridylic acid codes for

polyphenlylalanine. 1961 Marmur and Doty discovered DNA renaturation. 1962 1964 Racker isolated F1 ATPase from mitrochondria and reconstituted oxidative phosphorylation in submitchondrial vesicles. Acrylamide gel electrophoresis of proteins was developed.

1965 Marshal Nirenberg, H. Gobind Khorana and severo Ochoa completed the elucidation of the genetic code. 1965 1965 1965 3-D model of first enzyme (lysozyme by David Phillips). Robert Holley determined the structure of a transfer-RNA. Jerome Vinograd discovered superhelical twisting. Maizel introduced the use of sodium dodecylsulfate (SDS) for highresolution electrophoresis of protein mixtures.

1966

1966 Crick proposed the wobble hupothesis. 1966 Gilbert and Muller-Hill isolated the lac repressor. 1968 Mark Ptashne and Walter Gilbert identify the first repressor genes. 1968 Glomset proposed the theory of reverse cholesterol transport in which HDL is involved in the return of cholesterol to the liver.

Meselson and Yuan discovered the first DNA restriction enzyme. 1968 Shortly thereafter Smith and Wilcox discovered the first restriction enzyme that cuts DNA at a specific sequence. 1969 1969 Paula De Lucia and John Cairns isolated a mutant of E. colicalled pol A1. First synthesis of an enzyme (ribonuclease). Zubay and Lederman developed the first cell-free system for studying the regulation of gene expression. Hamilton Smith discovered restriction endonucleases. Temin and David Baltimore discovered reverse

1969 1970

1970 Howard

transcriptase. 1971 1972 1973 Vane discovered prostaglandins. that aspirin blocks the biosynthesis of

Jon Singer and Garth Nicolson proposed the fluid mosaic model for membrane structure. Stanley Cohen and Herbert Boyer prepared recombinant DNA.

1974 Sung-Hou Kim, et al. produced the first X-ray structure of transfer RNA. 1975 Brown and Goldstein receptor pathway. described the low-density lipoprotein

1975 Sanger and Barrel developed rapid DNA-sequencing methods. Michael Bishop and Harold Varmus discovered the c-src gene in 1976 uninfected cells, which is homologous to the v-src gene in the Ronus sarcoma virus. 1977 Cesar Milstein discovered how to produce monoclonal antibodies.

1977 Starlinger discovered the first DNA insertion element. 1977 Allan Maxam and sequencing DNA. Walter gibert developed chemistry for

1977 Fredrick Sanger, S. Nicklen and A.R. Coulson developed chemistry for sequencing DNA. 1977 McGarry, Mannaerts and Foster discovered that malonyl-CoA is a potent inhibitor of oxidation.

1977 Phillip Sharp and Richard Roberts discovered intons (intervening sequences). 1977 1978 1978 Nishizuka and Coworkers reported the existence of protein kinase C. Shortles and Nathans did the first experiments in directed mutagenesis. Tonegawa demonstrated DNA splicing for an immunoglobulin gene.

1981 Cech discovered RNA self-splicing.

1981 Steiz determined the structure of CAP protein. 1981 Palmiter and Brinster produced transgenic mice. 1982 First x-ray structure of a membrane protein. Mullis amplified DNA by the polymerase chain reaction (PCR) method. Schwartz and Cantor developed pulsed field gel electrophoresis for the separation of very large DNA molecules. Michel, Diesienhofer and Huber determined the structure of the photosynthetic reaction center. Blobel discovered the mechanism for protein translocation across the endoplasmic reticulum membrane-the signal hypthesis. Elion and Hitchings shared the Nobel prize for design and synthesis of therapeutic purines and pyrimidines. Synder and colleagues purified and reconstituted the inositol-1, 3, 4-P3 receptor.

1983 1984 1984 1984 1988 1989

Fishing in the stream of diabetes: from measuring insulin to the 1996 control of fetal organogenesis (C N Hales , M Desai , S E Ozanne , N J Crowther). 1996 Lessons from the discovery of the ubiquitin system (A Hershko). Advancing our knowledge in biochemistry, genetics, and 2001 microbiology through studies on tryptophan metabolism (C Yanofsky). 2001 The story of glutamine synthetase regulation (E R Stadtman). 2006 The mobility principle: biologist(Franois Gros). how I became a molecular