Biochemistry

Schematic representation of the DNA molecule, the molecule carrying genetic information.

Biochemistry is a branch of science that studies the chemical composition of living beings, especially proteins, carbohydrates, lipids and nucleic acids, as well as other small molecules present in cells and cells. chemical reactions that these compounds undergo (metabolism) that allow them to obtain energy (catabolism) and generate their own biomolecules (anabolism). Biochemistry is based on the concept that all living beings contain carbon and, in general, biological molecules are mainly composed of carbon, hydrogen, oxygen, nitrogen, phosphorus and sulfur.

It is the branch of science that studies the chemical basis of the molecules that make up some cells and tissues, which catalyze the chemical reactions of cell metabolism such as digestion, photosynthesis and immunity, among many other things.

We can understand biochemistry as an integrating scientific discipline that elaborates the study of biomes and biosystems. In this way, it integrates the chemical-physical laws and biological evolution that affect biosystems and their components. He does it from a molecular point of view and tries to understand and apply his knowledge to broad sectors of medicine (gene therapy and biomedicine), agri-food, pharmacology.

It constitutes a fundamental pillar of biotechnology, and has established itself as an essential discipline to address current and future major problems and diseases, such as climate change, the scarcity of agri-food resources due to the increase in world population, the depletion of fossil fuel reserves, the appearance of new allergies, the increase in cancer, genetic diseases, obesity, etc.

Biochemistry is an experimental science and for this reason it will resort to the use of numerous instrumental techniques of its own and those of other fields, but the basis of its development is based on the fact that what happens in vivo at the subcellular level is maintained or preserved after subcellular fractionation, and from there, we can study it.

History

19th century and first half of the 20th century

The history of biochemistry as we know it today is practically modern; Since the XIX century, a good part of biology and chemistry began to be directed towards the creation of a new integrating discipline: physiological chemistry or biochemistry. But the application of biochemistry and its knowledge probably began 5,000 years ago, with the production of bread using yeast, in a process known as fermentation.

It is difficult to approach the history of biochemistry, since it is a complex mixture of organic chemistry and biology, and sometimes it is difficult to distinguish between what is exclusively biological and what is exclusively organic chemistry, and it is evident that the contribution to this discipline has been very extensive. Although it is true that there are experimental data that are basic in biochemistry.

The beginning of biochemistry is usually located in the discoveries in 1828 of Friedrich Wöhler who published a paper about the synthesis of urea, proving that organic compounds can be created artificially, in contrast to the commonly accepted belief for a long time, that the generation of these compounds was possible only inside living beings.

Diastase was the first enzyme discovered. In 1833 it was extracted from the malt solution by Anselme Payen and Jean-François Persoz, two chemists from a French sugar factory.

In the middle of the 19th century, Louis Pasteur demonstrated the phenomena of chemical isomerism existing between the tartaric acid molecules from living beings and those chemically synthesized in the laboratory. He also studied the phenomenon of fermentation and discovered that certain yeasts were involved, and therefore it was not exclusively a chemical phenomenon as had been defended until now (including Liebig himself); Thus Pasteur wrote: "the fermentation of alcohol is an act related to the life and organization of the yeast cells, and not to the death and putrefaction of the cells." He also developed a method of sterilizing milk, wine and beer (pasteurization) and greatly contributed to refute the idea of spontaneous generation of living beings.

In 1869 nuclein was discovered and it was observed that it is a substance very rich in phosphorus. Two years later, Albrecht Kossel concluded that nuclein is rich in protein and contains the purine bases adenine and guanine and the pyrimidine bases cytosine and thymine. In 1889 the two major components of nuclein were isolated:

• Proteins (70 %)
• Acid substances: nucleic acids (30 %)

In 1878 the physiologist Wilhelm Kühne coined the term enzyme to refer to the unknown biological components that produced fermentation. The word enzyme was later used to refer to inert substances such as pepsin.

In 1897 Eduard Buchner began to study the ability of yeast extracts to ferment sugar despite the absence of living yeast cells. In a series of experiments at the Humboldt University of Berlin, he found that sugar was fermented even when there were no living elements in the yeast cell cultures. He called the enzyme that causes sucrose fermentation "zymase." By showing that the enzymes could function outside of a living cell, the next step was to demonstrate the biochemical nature of these biocatalysts. The debate was extensive; many, like the German biochemist Richard Willstätter, disagreed that protein was the enzyme catalyst, until in 1926, James B. Sumner demonstrated that the enzyme urease was a pure protein and crystallized it. The conclusion that pure proteins could be enzymes was definitively proven around 1930 by John Howard Northrop and Wendell Meredith Stanley, who worked with various digestive enzymes such as pepsin, trypsin, and chymotrypsin.

In 1903 Mikhail Tswett began studies on chromatography for the separation of pigments.

Around 1915 Gustav Embden and Otto Meyerhof carried out their studies on glycolysis.

In 1920 it was discovered that there is DNA and RNA in cells and that they differ in the sugar that is part of their composition: deoxyribose or ribose. DNA resides in the nucleus. A few years later, it is discovered that spermatozoa contain mainly DNA and proteins, and later Feulgen discovers that there is DNA in the chromosomes with its specific staining for this compound.

In 1925 Theodor Svedberg demonstrated that proteins are macromolecules and developed the analytical ultracentrifugation technique.

In 1928, Alexander Fleming discovered penicillin and carried out studies on lysozyme.

Richard Willstätter (circa 1910) studies chlorophyll and sees its similarity to hemoglobin. Later, around 1930, Hans Fischer investigated the chemistry of the porphyrins from which chlorophyll or the porphyrin group of hemoglobin derive. He managed to synthesize hemin and bilirubin. At the same time, Heinrich Otto Wieland formulates theories about dehydrogenation and explains the constitution of many other substances of a complex nature, such as pteridine, sex hormones or bile acids.

In the 1940s, Melvin Calvin concluded the study of the Calvin cycle in photosynthesis and Albert Claude the synthesis of ATP in mitochondria.

Around 1945 Gerty Cori, Carl Cori, and Bernardo Houssay completed their studies on the Cori cycle.

In 1953 James Dewey Watson and Francis Crick, thanks to previous studies with X-ray crystallography of DNA by Rosalind Franklin and Maurice Wilkins, and Erwin Chargaff's studies on nitrogenous base pairing, deduced the double helix structure of the DNA. In 1957, Matthew Meselson and Franklin Stahl show that DNA replication is semiconservative.

Second half of the 20th century

In the second half of the XX century, the real revolution of modern biochemistry and molecular biology began, especially thanks to to the development of the most basic experimental techniques such as chromatography, centrifugation, electrophoresis, radioisotopic techniques and electron microscopy, and more complex techniques such as X-ray crystallography, nuclear magnetic resonance, PCR (Kary Mullis), the development of immuno-techniques.

From 1950 to 1975, aspects of cell metabolism unimaginable up to now were known in depth and detail (oxidative phosphorylation (Peter Dennis Mitchell), urea cycle and Krebs cycle (Hans Adolf Krebs), as well as other metabolic pathways), a revolution took place in the study of genes and their expression; the genetic code is broken (Francis Crick, Severo Ochoa, Har Gobind Khorana, Robert W. Holley and Marshall Warren Nirenberg), restriction enzymes are discovered (late 1960s, Werner Arber, Daniel Nathans and Hamilton Smith), DNA ligase (in 1972, Mertz and Davis) and finally in 1973 Stanley Cohen and Herbert Boyer produced the first recombinant living being, thus giving birth to genetic engineering, converted into a very powerful tool with which the border between species is overcome and with which we can obtain a hitherto unthinkable benefit.

In 1970, an Argentine, Luis Federico Leloir, a physician, biochemist and pharmacist, received the Nobel Prize in Chemistry for his research on sugar nucleotides, and the role they play in the manufacture of carbohydrates.

In 1984, another Argentine, César Milstein, a native of the city of Bahía Blanca, received the Nobel Prize in Medicine for his research on monoclonal antibodies, today used to treat many diseases, including some types of cancer.

From 1975 to the beginning of the XXI century, DNA sequencing begins (Allan Maxam, Walter Gilbert and Frederick Sanger), the first biotechnological industries (Genentech) begin to be created, the creation of more effective drugs and vaccines increases, interest in immunology and stem cells rises and the enzyme telomerase is discovered (Elizabeth Blackburn and Carol Greider). In 1989 bioremediation was used on a large scale in the Exxon Valdez oil spill in Alaska. The first living beings are cloned, the DNA of dozens of species is sequenced and the complete human genome is published (Craig Venter, Celera Genomics and the Human Genome Project), tens of thousands of protein structures are resolved and published in PDB, as well as genes, in GenBank. The development of bioinformatics and the computation of complex systems begins, which are constituted as very powerful tools in the study of biological systems. The first artificial chromosome is created and the first bacterium with a synthetic genome is achieved (2007, 2009, Craig Venter). Nucleases are made with zinc fingers. Cells, which were not initially pluripotent, are artificially induced into pluripotent stem cells (Shin'ya Yamanaka). The first steps begin to be taken.

Branches of Biochemistry

Scheme of a typical animal cell with its orgies and structures.

The fundamental pillar of classical biochemical research focuses on the properties of proteins, many of which are enzymes. However, there are other disciplines that focus on the biological properties of carbohydrates (glucobiology) and lipids (lipobiology).

For historical reasons, the biochemistry of cell metabolism has been intensely investigated, in current important lines of research (such as the Genome Project, whose function is to identify and record all human genetic material), they are directed towards research DNA, RNA, protein synthesis, cell membrane dynamics, and energy cycles.

The branches of biochemistry are very broad and diverse, and have varied over time and with advances in biology, chemistry, and physics.

• Structural biochemistry: it is an area of biochemistry that aims to understand the chemical architecture of biological macromolecules, especially proteins and nucleic acids (ADN and RNA). This is how we try to know the peptide sequences, their three-dimensional structure and conformation, and the atomic physical-chemical interactions that enable these structures. One of its greatest challenges is to determine the structure of a protein knowing only the sequence of amino acids, which would provide the essential basis for the rational design of proteins (protein engineering).
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  Organic chemistry
  Organic chemistry: it is an area of chemistry that is responsible for the study of organic compounds (i.e. those that have carbon-carbon or carbon-hydrogen covalents) that come specifically from living beings. This is a science closely related to classical biochemistry, since most biological compounds share carbon While classical biochemistry helps to understand biological processes based on structure knowledge, chemical linkage, molecular interactions and reactivity of organic molecules, bioorganic chemistry attempts to integrate organic synthesis knowledge, reaction mechanisms, structural analysis and analytical methods with primary and secondary metabolic reactions, biosynthesis, cellular recognition and chemical diversity of living organisms. From there comes the Chemistry of Natural Products (V. Secondary Metabolism).
• Enzymology: studies the behavior of biological catalysts or enzymes, such as some proteins and certain catalytic RNAs, as well as coenzymes and cofactors such as metals and vitamins. This is how the mechanisms of catalysis, the processes of interaction of enzymes-sustrate, the states of catalytic transition, enzyme activities, the kinetic of reaction and the mechanisms of regulation and enzyme expression are questioned, all from a biochemical point of view. It studies and tries to understand the essential elements of the active centre and those who do not participate, as well as the catalytic effects that occur in the modification of these elements; in this sense, they frequently use techniques such as directed mutagenesis.
  • Metabolic biochemistry: is an area of biochemistry that aims to know the different types of metabolic paths at the cellular level, and their organic context. In this way they are essential knowledge of enzymology and cell biology. It studies all cell biochemical reactions that enable life, as well as healthy organic biochemical indices, the molecular bases of metabolic diseases or the flows of metabolic intermediaries globally. Academic disciplines such as bioenergy (a study of energy flow in living organisms), nutritional biochemistry (a study of nutrition processes associated with ASD metabolic routes) and clinical biochemistry (a study of biochemical alterations in the condition of disease or trauma). Metabolomy is the set of sciences and techniques dedicated to the complete study of the system constituted by the set of molecules that constitute metabolic intermediaries, primary and secondary metabolites, which can be found in a biological system.
• Xenobiochemical: is the discipline that studies the metabolic behavior of compounds whose chemical structure is not proper in the regular metabolism of a given organism. They may be secondary metabolites of other organisms (e.g. mycotoxins, snake poisons and phytochemicals when they enter the human organism) or rare or non-existent compounds in nature. Pharmacology is a discipline that studies xenobiotics that benefit cellular functioning in the organism due to its therapeutic or preventive effects (pharmaceuticals). Pharmacology has clinical applications when substances are used in the diagnosis, prevention, treatment and relief of symptoms of a disease as well as the rational development of less invasive and more effective substances against specific biomolecule targets. On the other hand, toxicology is the study that identifies, studies and describes, the dose, nature, incidence, severity, reversibility and, generally, the mechanisms of the adverse effects (toxic effects) produced by xenobiotics. At present toxicology also studies the mechanism of endogenous components, such as oxygen-free radicals and other reactive intermediaries, generated by xenobiotics and endobiotics.
• Immunology: area of biology, which is interested in the reaction of the organism to other organisms such as bacteria and viruses. All this taking into account the reaction and functioning of the immune system of living beings. The development of antibodies production and behaviour studies is essential in this area.
• Endocrinology: is the study of internal secretions called hormones, which are substances produced by specialized cells whose purpose is to affect the function of other cells. Endocrinology treats biosynthesis, storage and function of hormones, cells and tissues that secrete them, as well as hormonal signaling mechanisms. There are sub-disciplines such as medical endocrinology, plant endocrinology and animal endocrinology.
• Neurochemistry: is the study of the organic molecules involved in neuronal activity. This term is often used to refer to neurotransmitters and other molecules such as neuro-active drugs that influence neuronal function.
• Chemotaxonomy: is the study of the classification and identification of organisms according to their differences and demonstrable similarities in their chemical composition. The studied compounds can be phospholipids, proteins, peptides, heterosides, alkaloids and terpenes. John Griffith Vaughan was one of the pioneers of chemotaxonomy. Examples of the applications of chemotaxonomy include the differentiation of the families Asclepiadaceae and Apocynaceae according to the criterion of the presence of latex; the presence of agarofuranos in the family Celastraceae; sesquiterpenlactones with skeleton of germacran that are characteristics of the Asteraceae family or the presence of abietano plants in the aer parts Salvia of the Old World, unlike those of the New World, New-clerodans.
• Chemical ecology: is the study of chemical compounds of biological origin involved in interactions of living organisms. It focuses on the production and response of signaling molecules (semiochemicals), as well as compounds that influence the growth, survival and reproduction of other organisms (alelochemicals).
• Virology: area of biology, which is dedicated to the study of the most elementary biosystems: viruses. Both in its classification and recognition, and in its functioning and molecular structure. He intends to recognize targets for the performance of possible drugs and vaccines that prevent their direct or preventive expansion. They also analyze and predict, in evolutionary terms, the variation and combination of viral genomes, which could eventually make them more dangerous. Finally they represent a tool with a lot of projection as recombinant vectors, and have already been used in gene therapy.
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  Image: Mioglobin protein
  Molecular genetics and genetic engineering: it is an area of biochemistry and molecular biology that studies genes, their inheritance and their expression. Molecularly, it is dedicated to the study of DNA and RNA mainly, and uses powerful tools and techniques in its study, such as the RCP and its variants, mass sequesterers, commercial DNA and RNA extraction kits, transcription-translation processes in vitro and in vivo, restriction enzymes, ligaous DNA... It is essential to know how DNA is replicated, transcribed and translated into proteins (Central Dosage of Molecular Biology), as well as the mechanisms of basal and inducible expression of genes in the genome. It also studies the insertion of genes, gene silencing and the differential expression of genes and their effects. Thus surpassing the barriers and borders between species in the sense that the genome of one species can insert it into another and generate new species. One of its most current objectives is to know the mechanisms of regulation and genetic expression, that is, to obtain an epigenetic code. It is an essential pillar in all bioscientific disciplines, especially in biotechnology. Modern biotechnology has multiple applications and includes, in addition to the manufacture of medicines, food, paper, among others, the improvement of animals and plants of agronomic interest.
• Molecular Biology: is the scientific discipline that aims to study the processes that develop in living beings from a molecular point of view. As well as classical biochemistry closely investigates metabolic cycles and the integration and disintegration of molecules that make up living beings, molecular biology intends to be fixed with preference in the biological behavior of macromolecules (DN, RNA, enzymes, hormones, etc.) within the cell and to explain the biological functions of the living being by these properties at the molecular level.
• Cellular biology: (formerly) cytologyOf cites= cello and logos=Study or Treaty) is an area of biology that is dedicated to the study of morphology and physiology of prokaryotes and eukaryotic cells. Try to know its properties, structure, biochemistry composition, functions, orgies they contain, its interaction with the environment and its life cycle. It is essential in this area to know the intrinsic processes to cell life during the cell cycle, such as nutrition, breathing, synthesis of components, defense mechanisms, cell division and cell death. Cell communication mechanisms (especially in multicellular organisms) or intercellular unions should also be known. It is an area of observation and experimentation in cell cultures, which often aim to identify and separate cell populations and to recognize cellular orgánulos. Some techniques used in cell biology have to do with the use of cytochemical techniques, cell cultures sowing, observation by optical and electronic microscopy, immunocytochemistry, ELISA or flow cytometry.

Basic biochemical techniques

Being an experimental science, biochemistry requires numerous instrumental techniques that enable its development and expansion, some of which are used daily in any laboratory and others are very exclusive.

• Subcellular friction, include a multitude of techniques.
• Spectrophotometry
• Centrifuge
• Chromatography
• Electrophoresis
• Radioisotope techniques
• Flow cytometry
• Immunoprecipitation
• ELISA
• Electronic microscope
• X-ray crystallography
• Nuclear MRI
• Mass spectrometry
• Fluorimetry
• Nuclear Magnetic Resonance Spectroscopy

Expectations and challenges of biochemistry

Biochemistry is an experimental science that has a promising present and future, in the sense that it stands as the basis of biotechnology and biomedicine.

Biochemistry is basic for the formation of transgenic organisms and foods, bioremediation or gene therapy, and is constituted as a beacon and hope for the great challenges posed by the century XXI. There is no doubt that the changes it will bring will greatly benefit humanity, but the intrinsic fact that it is such powerful knowledge can make it dangerous. In this sense, areas such as bioethics that regulate morality and guide biological knowledge towards human benefit without moral transgressions.

Biochemical knowledge has great objectives such as progress in gene therapy, for example against cancer or HIV, developing more efficient, resistant, safe and healthy transgenic foods, applying biochemical knowledge to the fight against climate change and the extinction of species, generating new, more efficient drugs, researching and searching for disease targets, understanding gene expression patterns, generating new materials, improving the efficiency of industrial production...

Important Ibero-American biochemists

• Severo Ochoa
• Margarita Salas
• María Antonia Blasco Marhuenda
• Mariano Barbacid
• Jesus Grade Avila
• Carlos López Otín
• Eladio Viñuela
• Alberto Sols
• Santiago Grisolía García
• Luis Federico Leloir
• Andrea Gamarnik
• Alberto Kornblihtt
• Alejandra Bravo
• Francisco Bolívar Zapata
• Cesar Milstein
• Pablo Valenzuela
• Alexis Kalergis
• Cecilia Hidalgo Tapia
• Ramón Latorre

Etymology

The term biochemistry has a double origin and both agree. On the one hand, it comes from the French “biochimie”. On the other hand, it comes from the Greek “bios”, which means “life”, preceded by the word “chemistry”, which would eventually come from the Egyptian kēme, or from the Greek khymei- χῡμεία (etymology disputed) and whose meaning would be earth.