Organization of material on a metabolic map. Biochemical Power Basics Metabolic Map

This section contains 13 metabolic cards, on which the main metabolic paths are presented in compact and schematic form. Maps are not accompanied by any additional explanations.

Metabolic maps:

- allow to obtain a complete picture of a particular metabolic pathway, formed intermediate and finite compounds, as well as enzymes catalyzing biochemical reactions;

- Can serve as a reference material that allows you to determine the place of known substances in the metabolic paths.

The most important intermediate connections Schemes are numbered. The corresponding compounds can be easily identified using a concomitant table.

For each biochemical reaction, the classification code of the corresponding enzyme. The names and enzyme codes are also given in systematized list of enzymesin which all the enzymes mentioned in the text are arranged in accordance with their code. To identify enzymes, it is also recommended to use a substantial pointer.

For reactions involving co-effect The names of the coenzymes (partially in the trivial version) are given. For the most important initial, intermediate and end connections, full names or formulas are given.

Example

On the first metabolic map at the top of the left is the initial stage of the dark photosynthesis (Calvin cycle).

According to this reaction, from one molecule of ribulose-1,5-diphosphate (metabolite 1) and one CO 2 molecule (metabolite 2), two 3-phosphoglycerat molecules are formed (metabolite 3).

The code of the corresponding enzyme 4.1.1.39. From the list of enzymes it follows that we are talking about ribulozo Diffosfat carboxylase / Oxygenase (RDFKO, "Rubisko" or 3-Phospho-D-glycerat-carboxylase), a key enzyme of the reducing pentoso phosphate cycle of carbon assimilation during vehicles. RDFCO belongs to class 4 (lyases) and within this group to subclass 4.1 (carboxylysis). As a cofactor, the enzyme contains copper ().

Based on the results previously received by the University of California at San Diego, the international consortium of university scientists amounted to the most detailed virtual reconstruction of human metabolism. This model, called Recon 2, can be used to identify the causes and development of new methods for the treatment of diseases such as cancer, diabetes, and even psychiatric and neurodegenerative diseases.

Metabolism, or metabolism, each person, consisting in converting foods from food to energy and tissue, is determined by genetic factors, an exposure to the external environment and nutrition. For a long time, doctors recognized the exceptional importance of metabolic disorders in the development of diseases. And the data, in recent years, obtained by researchers, including those working on the so-called "project of the human genome" and in the field of systemic biology, are increasingly supporting this belief.

The developers compare Recon 2 with google cards, as they allow you to combine many small parts into a single interactive map. For example, experts studying the role of metabolism in the formation of conditions favorable for tumor growth can "bring closer" a certain fragment of the card to obtain detailed images of individual metabolic reactions, or remove it in order to understand the relationships between different signaling mechanisms and metabolic fragments.

The researchers have already demonstrated the practicality and functionality of such multi-level metabolic models of simple organisms, such as yeast and intestinal wand (E. coli). These models made it possible to create strains of microorganisms capable of synthesize large quantities of various compounds, such as ethanol, as well as predicting the development of drug resistance in drug bacteria.

One of the most promising areas of application Recon 2 is to determine the expression levels of certain genes, as well as the metabolic paths in which their protein products are involved, for the subsequent development of the methods of targeting drug delivery. Currently, there are already large databases containing information on gene expression in human cells undergoing active ingredients used in clinical practice and experimental preparations. Recon 2 allows specialists to use these available data in order to find out how defined drugs may affect those or other metabolic mechanisms, for example, conducive to the growth of malignant tumors. They are able to conduct virtual experiments that demonstrate the ability of drugs to restore metabolic disorders underlying the development of diseases.

Recon 1 - Prototype Recon 2 - was established in 2007 with six scientists at the University of California, working under the guidance of Professor Bernard Palsson (Bernhard Palsson). It included more than 3,300 known metabolic reactions, information about which was accumulated over the preceding 50 years. When creating Recon 2, this is the number of "cigned" metabolic reactions increased to more than 7,400. Recon 2 is in open access on the Recon X website.

According to Ines Thiele's Consortium, the former Graduate of the University of California, currently working at the University of Iceland, Recon 2 has already proved its functionality. With its help, metabolic disorders were successfully identified, to date, used to diagnose hereditary metabolic diseases.

Professor Tile believes that this fundamental resource, beyond any doubt, will make it possible to make many valuable forecasts that will speed up the transition of scientific experiments into clinical practice. According to her, the ultimate goal of the creation of Recon 2 is its use for personalization of diagnosis and treatment. In the future, doctors will be able to create individual metabolic diagrams of their patients based on it and select the most optimal therapeutic approaches to the treatment of various diseases, including diabetes, cancer and neurodegenerative diseases.

The Creators of Recon 2 recognize that there are still a lot of work ahead, since, despite the significant improvement compared to Recon 1, it contains information about 1,800 of about 20,000 coding proteins of human genome genes.

At the top - the central part of the map, downstairs - today's option, Recon 2.
How will the full map of all metabolic paths of the human body look like, imagine yourself.

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Scientists of the Weill Cornell Medical College in Qatar (WEILL Cornell Medical College in Qatar, WCMC-Q) were map of the metabolism of the human body, revealing the operation of metabolism as a system and possible ways to change the disease. Demonstrating various ways that bind genes, enzymes and metabolites, this card published in the journal Nature Genetics.shows that one or another drug whose target is one gene, can have several different effects on other ways.

One genetic difference in how the enzyme behaves, may have a positive or negative effect. It can make a person predisposed to the development of certain diseases or, on the contrary, protect it from some ailments.

This atlas shows that in terms of metabolism, each person is unique. Now we can really understand the genetic part of the human metabolism as a whole, "says Karsten Suhre, PhD, Professor of Physiology and Biophysics WCMC-Q, who worked on creating this card with his colleagues from European institutions.

Scientists of the Medical College of Vale in Qatar made a map of the metabolism of the human body, showing the work of exchange
Substances as systems and possible ways of its changes to treat diseases.
(Fig. WEILL CORNELL MEDICAL COLLEGE)

"If you want to change the levels of a certain metabolite in the treatment of a disease, such as diabetes or cancer, this card will tell you which enzyme should be the target. But she will tell you about what other metabolites and enzymes surrounding this target will be affected, and to achieve the desired effect, you can choose the desired combination of drugs, "comments the capabilities of the new atlas Professor Zer.

7824 people took part in this study, which helped scientists to identify 2.1 million genetic options. With the help of statistical analysis, it was established that 145 genes were able to significantly affect the functional activity of metabolism.

"Many of the 145 genes defined by us encode enzymes. Enzymes are needed for the formation of various metabolites - sugars, fats and amino acids that are the necessary organisms with construction blocks, "continues Dr. Zer. "Genetically, these enzymes have every person, but in terms of genetic code, all people are unique. Thus, creating a full picture of more than 400 metabolites for each blood sample we studied, we are looking for differences in what the enzymes of one or another person can do. "

The meaning of systematization based on symmetry is to make the latter obvious. The symmetry hidden in nature becomes available for direct perception, if it is possible to express through the symmetry of geometric forms. Therefore, the problem of systematization of biochemical information in this case is to depict the network of metabolic reactions in the form of symmetric graphics schemes, the same elements of which would reflect the similarity of the parts of its structure. This chapter will consider the metabolic map constructed on this principle. The separation of the metabolic network in the scheme corresponds to the traditional dismemberment of metabolism in accordance with the main classes of wildlife compounds: the exchange of carbohydrates, the exchange of amino acids and proteins, the exchange of lipids, the exchange of nucleic acids, etc. The schemes are based on the reaction grid obtained by combining simple symmetric forms on general compounds and reactions. The schemes are built in such a way as to emphasize the periodic nature of the structure of the metabolic network and the similarity of functionally similar compounds. For this purpose, the concepts of the period and a number are introduced. As periods, similar compounds related compound reactions are considered, when combining intervals of periodic reaction sequences, or vertical columns of lattice forms. Related periods are combined in the series. In the ranks there are functionally similar metabolites. The location of the individual schemes on the map is determined by the connections between them. The general map plan is presented in Fig.16.

In the upper region of the map there is a monosaccharide metabolic diagram. Its periods are indicated by Arabic numbers. The names of the series are shown on the left.

The average area of \u200b\u200bthe card has a complex structure. It is vertically divided into the upper and lower parts. The upper part is separated from the bottom digital and lettering designations of periods. Amino acid reactions and their nitrogen-containing derivatives are placed in the upper part. Here are the metabolism schemes of sulfur-containing compounds, as well as pyrimidine and purine derivatives. In the lower part, the reactions of bezazoty derivatives of amino acids are placed. The left side and the center of the middle area occupy the metabolism schemes of aliphatic compounds. On the right placed the schemes of metabolism of aromatic and heterocyclic derivatives.

The names of the common rows of the middle area are shown on the left. The names of the series belonging to the upper part of the central portion of the middle area are given between the schemes of the metabolism of aliphatic and aromatic compounds.

In the lower area of \u200b\u200bthe map, from left to right: the biosynthesis scheme of the main isoprene compounds, the metabolic diagrams of fatty acids and some lipids - derivative fatty acids and the biosynthesis scheme of the main porphyrin structures. These schemes are the development of the left and central parts of the middle area of \u200b\u200bthe map and are not connected with each other. The lower right corner of the map provides a list of symbols.

In general, along with simple compounds with a continuous carbon skeleton, a network of metabolic reactions includes complex products of their condensation: biopolymers, conjugation products, complex lipids and alkaloids. However, the lack of data on the chemical structure and biochemical transformations of these compounds makes it difficult to detect symmetry in the structure of their metabolism. Due to the lack of ability to present the metabolic diagrams of complex compounds in a symmetric form, they are not usually given on the map.

Studying biology in school, you probably have learned the fragments of the aerobic breathing scheme for some time - crebs cycle. If you did not fall asleep immediately, she had to leave you the impression that the power is a linear process.

Crebs cycle

At the entrance, we have carbohydrates, fats and proteins, and body cells are predictable to extract energy from them, produce useful metabolites and carbon dioxide and water are isolated. The arrows seem continuously as if the stages of the process took place equally the same. Although this model is useful for understanding the foundations, it is weakly consistent with reality. Food is a much more complex complex than it may seem when studying a static chart.

Once in trillions of the cells of our body, nutrients, as a rule, do not follow one predictable path. In most cases, their roads are branched, directly or indirectly, to many ways of products (metabolites), each of which can be branched on. Moreover, they can lead to various actions and functions, such as energy mobilization and recovery of damaged cells. The dominant path is largely determined, we are healthy or not. However, the understanding of metabolism is not only tracking a large number of independent paths for which the substance passes. When they are branched, their combinations look endless.

Maps of these metabolic maze decorate the walls of many research laboratories. Krebs's school cycle is a strongly simplified part of one of them. I have long been engaged in this and could observe the appearance of one of the most complex cards, which originated many years ago as a network of glucose metabolism reactions that lead to energy generation. The earliest version of this card was very useful for me when I taught biochemistry in the Virgin Polytechnic Institute in the 1960-190s. To describe a series of reactions leading from glucose to the Krex cycle at the bottom of the scheme (extraction of glucose energy), there was no less than a dozen lectures on the basics of biochemistry.

Glucose metabolism schemes

Difficult, right? But the map I enjoyed in the classroom - the insignificant part of our modern knowledge of the ways glucose metabolism. Over time, new reaction clusters have been added to it, including protein, fats and nucleic acid metabolism. Soon the reactions were so much, and the font decreased so much, which became clear: if you need to add something else, it is impossible to read the scheme with a naked eye. Cartographers began to create entire glucose metabolism atlas to take into account new discoveries. The fact that once was simple reactions now takes several pages of schemes.

These cards were made more detailed, until they became a symbol of how reductionism, in pursuit of detailed and specific information, lost sight of the whole. Scientists for years and decades worked on one or two reactions. On the map appeared tabs, on tabs - inserts, and, as we deepen into cellular metabolism, less forces remained to see the wisdom and the power of the system as a whole (Fig. 7.1).

Fig. 7.1. "Easy" scheme of glucose metabolism paths

The word "reductionism" is a single root with the Latin phrase of the Reductio Ad Absurdum, "bringing to the absurd". Remember a simple, but at the same time complex glucose metabolism scheme? Here is its updated version (Fig. 7.2).

Fig. 7.2. One of the latest glucose metabolic paths

Scientists, however, went further. Evaluate the complexity of a very small piece of a map enlarged for intelligibility (Fig. 7.3). A more complete metabolic card in Fig. 7.2 - Small part of all reactions in each of the hundreds of trillion cells of our body.

I emphasize the complexity of metabolism so that you see: it is impossible to fully understand how our body reacts to the products that we eat and the nutrients contained in them. The explanation of the nutrient functions of only one or even a pair of these reactions is not enough. After consumption, they interact with each other and other substances in the maze of metabolic reactions occurring in this hundredth trillion cells. For the action of a particular nutrient, some separate reaction or mechanism does not respond. All of them and many other substances associated with them are involved in cellular metabolism and are converted into numerous products with high-infected paths - no less complicated than in Fig. 7.1-7.3.

Fig. 7.3. Increased map fragment

Each substance passes the reaction labyrinth, so it can be a factor of effect on well-being. The connection "One substance is one disease" that reductionism implies, popular, but incorrect.