The word biochemistry appeared around the end of 19 and the beginning of the 20th century, but its origin can be traced back further, and its early history is a part of the early physiological and chemical history. For example, in the 1980s of 18, A.-L. lavoisier proved that respiration is as oxidation as combustion. Almost at the same time, scientists found that photosynthesis is essentially the reverse process of animal respiration. For example, in 1828, F. Waller synthesized an organic substance-urea for the first time in the laboratory, which broke the view that organic matter can only be produced by organisms and caused a great blow to the theory of vitality. 1860 L. Pasteur proved that fermentation was caused by microorganisms, but he thought that there must be live yeast to cause fermentation. 1897, brothers Bishner discovered that the cell-free extract of yeast can be fermented, which proved that complex life activities such as fermentation can be carried out without living cells, and finally overturned the "vitality theory".
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classify
Biochemistry can be divided into animal life if it is aimed at different organisms.
Chemistry, plant biochemistry, microbial biochemistry, insect biochemistry, etc. If we study different tissues or processes of organisms, they can be divided into muscle biochemistry, neurobiochemistry, immune biochemistry, biomechanics and so on. Because of the different substances studied, it can be divided into protein chemistry, nucleic acid chemistry, enzymology and other branches. The chemical study of various natural substances is called bioorganic chemistry. The subject that studies the biological functions of various inorganic substances is called bioinorganic chemistry or inorganic biochemistry. Since the 1960s, the integration of biochemistry and other disciplines has produced some marginal disciplines, such as biochemical pharmacology, paleontology and chemical ecology. Or according to different application fields, it can be divided into medical biochemistry, agricultural biochemistry, industrial biochemistry, nutritional biochemistry and so on.
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research contents
Biochemistry mainly studies the molecular structure and function of objects, the metabolism and regulation of substances, the molecular basis and regulation law of genetic information transmission.
Chemical composition of organisms
In addition to water and inorganic salts, organic substances in living cells are mainly composed of carbon atoms combined with hydrogen, oxygen, nitrogen, phosphorus and sulfur, which are divided into macromolecules and small molecules. The former includes protein, nucleic acid, polysaccharide and lipid in a combined state; The latter includes vitamins, hormones, various metabolic intermediates and amino acids, nucleotides, sugars, fatty acids and glycerol needed for biomacromolecules synthesis. In different organisms, there are various secondary metabolites, such as terpenoids, alkaloids, toxins, antibiotics and so on.
Although the identification of biological components is a feature of the early development of biochemistry, until today, new substances are still being discovered. Such as interferon, cyclic nucleoside phosphate, calmodulin, mucin, lectin, etc., have become important research topics. Some simple molecules were found in 1980, such as fructose 2,6-diphosphate as a metabolic regulator. On the other hand, compounds that have long been known will also find new functions. Carnitine was discovered in the early 20th century, and it was not called growth factor until 1950s, but it was called the carrier of biological oxidation in 1960s. Putrescine and cadaverine, and polyamines such as spermine and spermidine, which have been considered as decomposition products for many years, have been found to have many physiological functions, such as participating in the regulation of nucleic acid and protein synthesis, stabilizing DNA supercoils, and regulating cell differentiation.
Metabolism and metabolic regulation control
Metabolism includes anabolism and catabolism. The former is a process in which organisms obtain substances from the environment and transform them into new substances in the body, which is also called assimilation; The latter is the transformation of the original substance in the organism into the substance in the environment, which is also called alienation. The process of assimilation and alienation consists of a series of intermediate steps. Intermediate metabolism is the study of chemical pathways. For example, the alienation of glycogen, fat and protein is decomposed into glucose, fatty acids and amino acids through different ways, and then oxidized into acetyl coenzyme A, which enters the tricarboxylic acid cycle and finally produces carbon dioxide.
In the process of material metabolism, there are also changes in energy. The mutual transformation and change of mechanical energy, chemical energy, thermal energy, light and electricity in organisms is called energy metabolism, and ATP plays a core role in this process.
Metabolism is carried out in an orderly manner under the control of organisms. There are three ways for this regulation: ① controlling the synthesis of enzymes through the induction or repression of metabolites. This is an enzyme related to the regulation of transcription level, such as lactose-induced lactose operon synthesis; ② Through the interaction between hormones and target cells, a series of biochemical processes are triggered, such as cyclic adenylate-activated protein kinase regulating glucose metabolism through phosphorylation; ③ Effectors directly affect the activity of enzymes through allosteric effects, such as the feedback inhibition of end products on the first enzyme in metabolic pathway. Most of the regulation processes in organisms are realized through allosteric effects.
Structure and function of biological macromolecules
The diverse functions of biological macromolecules are closely related to their specific structures. The main functions of protein are catalysis, transportation and storage, mechanical support, exercise, immune protection, receiving and transmitting information, regulating metabolism and gene expression. Due to the progress of structural analysis technology, people can deeply study their various functions at the molecular level. The research on the catalytic principle of enzymes is a prominent example in this respect. The structure of protein molecule can be divided into four levels, in which there can be a super secondary structure between the secondary and tertiary structures and a domain between the tertiary and tertiary structures. Domains are relatively compact regions with special functions, and the peptide chain connecting domains has certain movement space, allowing some relative movement between domains. Protein's side chain has been moving rapidly. The internal mobility of protein molecules is an important basis for them to perform various functions.
Protein Project, which appeared in the early 1980s, obtained modified protein molecules at designated sites by changing the structural genes of protein. This technology not only provides a new way to study the relationship between structure and function of protein; But also opens up a broad prospect for synthesizing new protein with specific functions according to certain needs.
The study on the structure and function of nucleic acid is helpful to clarify the nature of genes and understand the flow of biological genetic information. Base pairing is the main form of interaction between nucleic acids and the structural basis of nucleic acids as information molecules. The double helix structure of deoxyribonucleic acid has different conformation. J. D. Watson and F.H.C C. Crick discovered the right-handed helix of B structure, and later discovered the left-handed helix called Z structure. DNA also has a supercoiled structure. These different conformations have their functional significance. Ribonucleic acid, including messenger ribonucleic acid (mRNA), transfer ribonucleic acid (tRNA) and ribosomal ribonucleic acid (rRNA), plays an important role in protein biosynthesis. Recently, it has been found that a single RNA has the function of an enzyme.
The regulation of gene expression is the central issue of molecular genetics research, and it is also an important content of nucleic acid structure and function research. There is a lot of knowledge about gene regulation in prokaryotes. The regulation of eukaryotic genes is being discussed from many aspects. Such as heterochromatization and chromatin activation; Conformational changes and chemical modifications of DNA; The role of regulatory sequences such as enhancers and regulators on DNA; Regulation of RNA processing and translation.
Carbohydrates in organisms include polysaccharides, oligosaccharides and monosaccharides. Among polysaccharides, cellulose and chitin are structural substances of plants and animals, while starch and glycogen are stored nutrients. Monosaccharide is the main energy source of organisms. The importance of oligosaccharides in structure and function was not recognized until 1970s. Oligosaccharides and protein or lipids can form glycoproteins, proteoglycans and glycolipids. Because of the complexity of sugar chain structure, they have great information capacity and play an important role in cell-specific recognition and interaction of certain substances, thus affecting cell metabolism. From the development trend, sugar will become the four major research objects of biochemistry together with protein, nucleic acid and enzyme.
Once the chemical structure of biological macromolecules is determined, it can be synthesized artificially in the laboratory. The artificial synthesis of biomacromolecules and their analogues is helpful to understand the relationship between their structure and function. Some analogues may have application value because of their high biological activity. Artificial genes obtained by chemically synthesizing DNA can be applied to genetic engineering to obtain protein and its analogues with important functions.
Enzymology research
Almost all chemical reactions in organisms are catalyzed by enzymes. The function of enzyme has the characteristics of high catalytic efficiency and strong specificity. These characteristics
Depending on the structure of the enzyme. The relationship between enzyme structure and function, reaction kinetics and mechanism, and regulation of enzyme activity are the basic contents of enzymology research. Through X-ray crystallographic analysis, chemical modification and kinetic study, the action principles of some representative enzymes have been clarified. Specific irreversible inhibitors developed in 1970s, such as affinity labeling reagents and suicide substrates, have become effective tools to explore the active sites of enzymes. The synergistic effect of various enzymes in multienzyme system, the interaction between enzymes and biological macromolecules such as protein and nucleic acid, and the application of protein engineering to study the structure and function of enzymes are several new directions of enzymology research. Enzymes are closely related to human life and production activities, so the application of enzymes in industrial and agricultural production, national defense and medicine has received extensive attention.
Biofilm and Biomechanics
Biofilm is mainly composed of lipids and protein, and generally contains sugars. Its basic structure can be expressed by fluid mosaic model, that is, lipid molecules form a double-layer membrane, and membrane proteins interact with lipids to varying degrees and can move laterally. Biofilm is closely related to energy conversion, material and information transmission, cell differentiation and division, nerve conduction and immune response. It is an active research field in biochemistry.
Taking energy conversion as an example, in biological oxidation, metabolites are oxidized by electron transfer in respiratory chain, and the generated energy is stored in high-energy compound ATP through oxidative phosphorylation to meet the needs of energy-consuming reactions such as muscle contraction. Mitochondrial intima is the location of respiratory chain oxidative phosphorylase system and plays a power station role in cells. In photosynthesis, ATP is produced by photosynthetic phosphorylation in chloroplast membrane. These studies constitute the main content of biomechanics.
Hormones and vitamins
Hormone is an important regulator of metabolism. Hormone system and nervous system constitute two main communication systems of organisms, and they are closely related. Since 1970s, the research scope of hormones has been expanding day by day. If it is found that cells in the gastrointestinal tract and nervous system can also secrete hormones; Some growth factors and neurotransmitters are also contained in hormones. The chemical structures of many hormones have been determined, and they are mainly peptides and steroid compounds. The mechanism of action of some hormones is also understood, some are to change the permeability of membranes, some are to activate the enzyme system of cells, and some are to affect the expression of genes. Vitamins also have an important influence on metabolism, which can be divided into water-soluble and fat-soluble categories. Most of them are auxiliary groups or coenzymes of enzymes, which are closely related to the health of organisms.
The origin and evolution of life
According to the theory of biological evolution, millions of species on the earth have the same origin and were gradually formed in the process of evolution of about 4 billion years. The development of biochemistry provides strong evidence for this theory at the molecular level. For example, the DNA of all species contains the same nucleotide. Many enzymes and other protein exist in various microorganisms, plants and animals, with similar amino acid sequences and similar three-dimensional structures, and the similarity is consistent with the genetic relationship among species. Errors in DNA replication can explain how variation, which is the basis of evolution, occurs. When organisms evolve from lower to higher levels, they need more enzymes and other protein. Gene rearrangement and mutation provide the possibility to adapt to this need. It can be seen that the study of biochemistry on evolution will provide more essential and quantitative information for clarifying the mechanism of evolution.
Methodology
In the development of biochemistry, many important advances are due to breakthroughs in methods. For example, isotope tracer technology is used for metabolic research and structural analysis; Chromatography, especially high performance liquid chromatography, has greatly improved the performance of the system since 1970s, and various electrophoresis techniques have been used for the separation and purification of protein and nucleic acids and the determination of primary structures. X-ray diffraction technique is used to determine the crystal structure of protein and nucleic acid. High-resolution two-dimensional nuclear magnetic resonance technology is used to analyze the conformation of biological macromolecules in solution; Enzymatic method is used for DNA sequence determination; Monoclonal antibodies and hybridoma techniques were used to isolate and purify protein and to study antigenic determinants in protein. Since the 1970s, computer technology has penetrated into various fields of biochemistry extensively and rapidly, which not only greatly improved the automation and efficiency of many analytical instruments, but also provided a brand-new means for the structure analysis, structure prediction and structure-activity relationship research of biological macromolecules. The continuous development of biochemistry in the future will undoubtedly benefit from the innovation of technology and methods.