Cell XIX. Metabolism

Among the most important features of living matter, its subjects (objects, organisms) stand out from all possible exchanges of information, matter and energy with the external environment, which serve as the basis for the life activity of organisms. In addition, a set of processes of regulation, transformation of substances and transformation of energy occurs directly in the subjects themselves – living organisms. Such flows of information (control, regulation), matter and energy between the inorganic environment and the biosphere formed by living organisms are always controlled and regulated by multi-level regulatory information systems. And they ensure that chemical reactions with many different enzymes are ordered in time and in cellular space.
Five characteristics of living systems are commonly named: 1. Openness (living systems exchange energy, information, and matter with the environment) 2. Self-reproduction 3. Self-regulation (homeostasis; systems do not require regulation
from outside) 4. Self-renewal (systems evolve over time) 5. Highly ordered

At the cellular level, reactions occur sequentially in strictly defined areas of cells, which is ensured by the principle of cell compartmentation.

Compartmentalization (compartmentation) – division of eukaryotic cells into compartments (compartments: mitochondria, chloroplasts, peroxisomes, lysosomes, endoplasmic reticulum, cell nucleus And Golgi apparatus.), covered with a membrane of lipid bilayer, in which certain biochemical processes are localized. In the compartments themselves (including the nuclei) are also secreted subcompartmentsdiffering in form and function[1].

The purpose of the publication is primarily educational, cognitive, to facilitate independent mastery of fundamental ideas and scientific concepts, the popularization of science, as well as the desire to attract an influx of new young (and not so young) minds into the ranks of researchers, into science, to arouse in such minds a desire to find answers to emerging questions. The scale of the topic requires the introduction of reasonable restrictions.

Introduction

Life on planets in the habitable region is possible subject to the use of matter, information and energy from the environment, which undergo transformations by organisms and become suitable for their existence and development. Metabolism, or metabolism, is primarily the chemical reactions that support life in a living organism and on the planet as a whole. These processes allow organisms to grow and reproduce, maintain their structures, and respond to environmental influences. Metabolic rate affects the amount of food needed for the body to function.

Consider 2 aspects of metabolism: catabolism And anabolism. During catabolism
complex organic matter decompose into simpler ones, usually releasing energy, and in the processes anabolism — more complex substances needed by the body are synthesized from simple ones with energy expenditure. In this case, the role of regulatory effects and various numerous enzymes, without which metabolism would be impossible, is great. Enzymes act as biological catalysts and reduce activation energy

chemical reaction; allow the regulation of metabolic pathways (a series of chemical reactions) in response to changes in the environment cells or signals from other cells. The cyclical nature of such processes, both on a global (change of seasons) and organismal (for example, the Krebs cycle) scale, is of great importance. This is something similar to the Carnot cycle in technology (in internal combustion engines).

IN Wikimedia Commons exists diagram depicting a large set of metabolic pathways in the human body. Metabolism is classically studied simplified approach that focuses on a single metabolic pathway. The reactions of a substance (pathways) are tracked using labeled atoms at the organismal, tissue, and cellular levels that define pathways from precursors to end products by identifying radioactively labeled intermediates. The current state of the theory was preceded by a long history of insights and discoveries.

Chronology

1754 Carbon dioxide discovered (J. Black)
1766 Hydrogen discovered (G. Cavendish)
1778 Oxygen production by plants discovered (J. Priestley)
1814 It was established that barley extract converts starch into sugar with enzymes (G. Ktrkhoff)
1839 Liebig Yu. on the “non-living” nature of enzymes
1854 T. Graham (Scotland) method of making semi-permeable parchment membranes.
1862 The photosynthetic origin of starch is shown (J. Sachs)
1868 Nucleic acids discovered (F. Miescher)
1871 It was established that proteins consist of amino acids (N.N. Lyubavin)
1871 The ability to convert sugar into alcohol belongs not to cells, but to enzymes (M. Manasseina)
1875 Oxidation processes occur in tissues, not in blood (E. Pfluger).
1887 Chemosynthesis was discovered (S. N. Vinogradsky)
1893 Rev. Nitrifying bacteria and their role in the nitrogen cycle (S. N. Vinogradsky)
1902 Overton discovers lipids in the plasma membrane.
1903 Establishment of the role of plants in the cosmic circulation of energy and matter K. A. Timiryazev
1904 D. Abel (USA) created a device (filter) for removing substances dissolved in the blood.
1910 The unity of the processes of fermentation and respiration was proven (S.P. Kostychev)
1913 D. Abel (USA) created a hemodialysis machine, which became the prototype of an artificial kidney.
1923 Photosynthesis – redox reaction (T. Thunberg)
1924 G. Haas (Germany) the first hemodialysis for a person with uremia, an anticoagulant – hirudin.
1925 G. Haas produced a batch of heparin from the liver.
1925 Gorter and Grendel show the presence of a lipid bilayer in the red blood cell membrane.
1926 The work of V.I. is published. Vernadsky “Biosphere”
1927 by G. Haas. For the first time in hemodialysis, heparin was used as an anticoagulant.
1926 Transforming factor (TF) was discovered. Foreign DNA changed the properties of bacteria.
1935, “Sandwich” model of Danielli, Dawson (lipid bilayer between 2 layers of proteins).
1937 The citric acid cycle, later called the Krebs Cycle, was described by Hans A. Krebs.
1944 Avery's lab proved the identity of TF and DNA, which Griffiths was unable to do with his discovery of TF.
1944 V. Kolff (Holland) was the first to successfully use an artificial kidney in surgery.
[1945VKolf(Holland)removalofapersonfromuremiccomausinghemodialysis
1946 W. Colff first manual on the treatment of patients with uremia using hemodialysis.
1948 Substantiation of the unity of management principles in cybernetic systems and living organisms (N. Wiener).
1960 B Scribner, V Quinton Chronic hemodialysis by implantation in radial artery
And subcutaneous vein two Teflon tubes
1962, Muller creates a flat model of an artificial membrane 1957-1963, Robertson formulates the concept of an elementary biological membrane.
1972 Creation of the fluid mosaic membrane model by Singer and Nicholson.
1980 T. Agishi and colleagues (Japan) proposed a filter for separating already obtained plasma into low- and large-molecular fractions.
2001 Plasma filter “Rosa”, developed and produced in the Moscow region,
2004 C. Jennings tests an implantable device (ID) in a laboratory setting.
2006 C. Jennings Patent No. US7083653 B2 (IP) is registered in the US Patent Office.
2009 IP portable device; Battery operation for 6-8 hours, weight 4 kg
2010 In the USA, a hemodialysis machine that can be implanted into the patient’s body is developed.
2011 Kidney transplantation around the world
2013 H. Otto et al. grew an artificial kidney using a bioengineering method.
2013 Plasma filter “Hemos-PFS”, consisting of spirally wound composite membranes.

Metabolism

Rice.  1. Basic principles and elements of metabolism

Fig. 1. Basic principles and elements of metabolism

Catabolism. Catabolism is the metabolic process in which relatively large organic molecules of sugars, fats, and amino acids are broken down into their constituent components. Cellular and catabolism are studied in detail. It is realized with the release of energy contained in the chemical bonds of organic molecules and its reservation in the form of energy in the phosphate bonds of the adenosine triphosphate (ATP) molecule.

Catabolism (energy metabolism, dissimilation one side of metabolism (metabolism), occurring in any living cell. This is the process of breakdown of complex organic substances (food, reserve), carried out gradually in three stages:

1) preparatory; polymeric organic molecules break down into their constituent specific structural blocks – monomers.

Thus, polysaccharides are broken down into hexoses or pentoses, proteins into amino acids, nucleic acids into nucleotides and nucleosides, lipids into fatty acids and glycerol. These reactions proceed mainly hydrolytically and the amount of energy released at this stage does not exceed 1% of the total energy released during catabolism, and is almost entirely used by the body as heat.

2) anoxic (glycolysis); the products of chemical reactions are even simpler molecules, unified for carbohydrate, protein and lipid metabolism. by their type (glycolysis, amino acid catabolism, β-oxidation of fatty acids, respectively). The fundamental thing is that at the second stage (stage) of catabolism, products are formed that are common for the metabolism of initially different groups of substances.

These products are key chemical compounds that connect different metabolic pathways. Such compounds include, for example, pyruvate (pyruvic acid), formed during the breakdown of carbohydrates, lipids and many amino acids, acetyl-CoA, which combines the catabolism of fatty acids, carbohydrates and amino acids, a-ketoglutaric acid, oxaloacetate (oxaloacetic acid), fumarate (fumaric acid). acid) and succinate (succinic acid), formed during the transformation of amino acids.

Products obtained at the second stage of catabolism enter third stagewhich is known as the tricarboxylic acid cycle (terminal oxidation, citric acid cycle, Krebs cycle).

3) oxygen; acetyl-CoA and some other metabolites, for example α-ketoglutarate, oxaloacetate, undergo oxidation in the Krebs di- and tricarboxylic acid cycle. Oxidation is accompanied by the formation of reduced forms of NADH + H+ and FADH2.

It is during the second and third stages of catabolism that virtually all the energy of chemical bonds of the substances subjected to dissimilation is released and accumulated in the form of ATP. In this case, electrons are transferred from the reduced nucleotides to oxygen through the respiratory chain, accompanied by the formation of the final product – a water molecule. Electron transport in the respiratory chain is associated with the synthesis of ATP in the process of oxidative phosphorylation.

In this case, enzymes are necessarily involved and the energy necessary for the synthesis of ATP and warming the body (thermal) is released. All the energy needed by a heterotrophic organism for life is obtained as a result of the breakdown of organic food substances. The more physical activity the body experiences, the more energy the food should contain and, conversely, with light physical activity the food should be low in calories.

Some catabolic reactions are practically irreversible, since their reverse course is prevented by insurmountable energy barriers. Therefore, in the course of evolution, other reactions specific to anabolism were developed, where the synthesis of oligo- and polymeric compounds is associated with the expenditure of energy of macroergic compounds, primarily ATP.

Anabolism (Greek “anabol” – rise) – plastic exchange, assimilation is the other side of metabolism. Includes the processes of synthesis of amino acids, monosaccharides, fatty acids, nucleotides, as well as macromolecules of proteins, polysaccharides, fats, nucleic acids, ATP.

The process takes place in three stages:

1) synthesis of intermediate compounds from low molecular weight substances (organic acids, aldehydes). In this case, the starting substances for anabolic processes are the products of the second stage and intermediate compounds of the third stage of catabolism. ; The first, initial stage (stage) of anabolism is the chemical reactions occurring in a given place and at a given time, which essentially perform a double function.

On the one hand, they are the basis for the final stage of catabolism, and on the other, they serve as an initiation for anabolic processes, supplying precursor substances for subsequent stages of assimilation. In a similar way, for example, protein synthesis begins. The initial reactions of this process can be considered the formation of some a-keto acids.

2) synthesis of “building blocks” from intermediate compounds (amino acids, fatty acids, monosaccharides); during amination or transamination reactions, these keto acids are converted into amino acids, which in the third stage of anabolism are combined into polypeptide chains.

As a result of a series of successive reactions, the synthesis of nucleic acids, lipids and polysaccharides also occurs. However, it should be emphasized that the anabolism pathways are not a simple reversal of the catabolic processes.

3) synthesis of “building blocks” of macromolecules of proteins, nucleic acids, polysaccharides, fats. It occurs with the absorption of energy and the participation of enzymes. Anabolism carries out the enzymatic synthesis of large-molecular cellular components, such as polysaccharides, nucleic acids, proteins, lipids, as well as some of their biosynthetic precursors from simpler compounds. Anabolic processes occur with the consumption of energy.

The processes of catabolism and anabolism occur in cells simultaneously, are inextricably linked with each other and are essential components of one general process – metabolism, in which the transformations of substances are closely intertwined with the transformations of energy (potential, kinetic, thermal, electrical, etc.). Mechanical, chemical, electrical and other processes are implemented (take place) in compartments cells.

Due to different localizations, catabolic and anabolic processes in the cell can occur simultaneously. Moreover, all transformations of organic substances, processes of synthesis and decomposition are interconnected, coordinated and regulated neurohormonal mechanisms, giving chemical processes the desired direction.

The following cells are usually distinguished: compartments:

  1. Core (internal contents of the kernel)

  2. Space of the cisterns of the endoplasmic reticulum (transitioning into the perinuclear space)

  3. Golgi apparatus mainly transport of substances from EPS,protein transport and formation lysosomes.

  4. Mitochondria (divided into two compartments – the matrix and the intermembrane space)

  5. Peroxisomes – contain enzymes that, with the help of oxygen, oxidize some organic substances.

  6. Lysosomes – intracellular digestion of macromolecules, including autophagy.

  7. Chloroplasts (in higher plants they are divided into three compartments – the intermembrane space, the stroma and the internal cavity of the thylakoids)

  8. Cytosol – the same hyaloplasm – the liquid part of the cytoplasm. It is a complex mixture of substances dissolved in the liquid.

The physiological needs of the body, as well as the expediency of replacing some classes of organic substances with others, dictate the existing interconversions of substances and energies. There is no independent metabolism of proteins, fats, carbohydrates and nucleic acids in the human body. All transformations are combined into an integral metabolic process, which also allows for interconversions between individual classes of organic substances.

Enzymes or Enzymes – These are specialized proteins. The main task of an enzyme is to help a reaction proceed as quickly as possible. It is thanks to enzymes that cells do not need high temperatures, pressure or any other special conditions. Enzymes provide the necessary energy (the so-called “activation energy”) for complex biochemical processes.

The main catabolic process in metabolism is considered to be biological oxidation – a set of oxidation reactions that occur in all living cells – namely respiration and oxidative phosphorylation. An integral characteristic of biological oxidation is the so-called respiratory coefficient (RQ), which is the ratio of the volume of carbon dioxide released by the body to the volume of simultaneously absorbed oxygen.

During oxidation of carbohydrates, the volume of oxygen consumed corresponds to the volume of carbon dioxide formed, and therefore the respiratory quotient in these cases is equal to one. During oxidation of fats and proteins, such a correspondence is absent, since in addition to oxidation of carbon to carbon dioxide, part of the oxygen is spent on oxidation of hydrogen with the formation of water.

As a result, the values ​​of the respiratory coefficient in the case of oxidation of fats and proteins are approximately 0.7 and 0.8, respectively. The overwhelming majority of protein nitrogen during protein oxidation in the body turns into urea. Therefore, based on the respiratory coefficient and data on the amount of urea released, it is possible to determine the ratio of carbohydrates, fats and proteins participating in the biological oxidation.

About the molecule adenosine triphosphate (ATP). Oxidative phosphorylation – the process of ATP formation on cell membranes. ATP consists of the nitrogenous base adenine, the carbohydrate ribose and three phosphoric acid residues linked together by high-energy bonds. ATP formation is associated with the oxidation of reduced carriers (for example, NADH2 to NAD; NADPH2 to NADP) and electron transfer in the electron transport network.

The designations for coenzymes used here are:
NAD – nicotinamide adenine dinucleotide;
NADP – nicotinamide adenine dinucleotide phosphate;
FAD – flavin adenine dinucleotide.

There are also distinctions substrate phosphorylation – the process of ATP formation outside cell membranes. In this case, ATP is formed due to the fact that the phosphate group moves from the phosphorylated compound (substrate) to ADP (for example, the formation of ATP during glycolysis).

Figure 2 - The structure of the ATP molecule and its lifespan

Figure 2 – The structure of the ATP molecule and its lifespan

Breathing – a chain of physiological processes occurring in the body of plants and animals, during which oxygen is absorbed, carbon dioxide and water are released, as well as energy that ensures the life of the organism. In animals, a distinction is made between external respiration (respiratory organs and airways) and intracellular respiration (mitochondria), since oxygen is absorbed only in mitochondria. In plants, respiration is carried out by all organs, but oxygen is also absorbed only in the mitochondria of cells. Here it is included in the electron transport chain, adding protons, the kinetic energy of which was spent on the synthesis of ATP. This is the oxygen dissimilation stage (catabolism), which is why mitochondria are called the respiratory centers of cells.

Cellular metabolism is characterized by four main specific functions, namely:

  • energy extraction from the environment and

  • transformation it into the energy of macroergic (high-energy) chemical compounds in an amount sufficient to meet all the energy needs of the cell;

  • education from exogenous intermediate substances connectionswhich are precursors of high-molecular cellular components;

  • synthesis from these precursors of proteins, nucleic acids, carbohydrates, lipids and other cellular components; synthesis and destruction of special biomolecules, the formation and breakdown of which are associated with the performance of specific functions of a given cell.

It is customary to highlight accordingly external, or general, exchange substances And internal or intermediate, exchange substances. In turn, both in internal and external metabolism, a distinction is made between structural (plastic) and energy metabolism.

Catabolic and anabolic reactions differ, as a rule, in their location in the cell. For example, the oxidation of fatty acids to carbon dioxide and water is carried out by a set of mitochondrial enzymes, whereas the synthesis of fatty acids is catalyzed by another system of enzymes located in the cytosol.
Many metabolic processes are carried out cyclically, a striking example is the tricarboxylic acid cycle – the Krebs cycle.

The citric acid cycle was described by biochemist Hans Adolf Krebs in 1937 and is therefore also called the Krebs cycle.

The tricarboxylic acid cycle (abbreviated TCA cycle, Krebs cycle, citrate cycle, citric acid cycle) is the central part of the general catabolic pathway, a cyclic biochemical process during which acetyl residues (CH3CO-) are oxidized to carbon dioxide (CO2).

Here the substrates of the reactions of the tricarboxylic acid cycle are sequentially encrypted:
PIKE (oxaloacetic acid) ACETYL-coenzyme A CITRIC acid
CISACONITIC ACID, ISOLYMIC ACID, ALPHA-KETOGLUTARIC ACID. SUCCINYL-COENZYME A, SUCCINIC ACID, FUMARIC ACID, MALIC ACID, OXALOACETIC ACID
A very short poem was composed to help students remember this cycle:
PIKEat ACETILLIMONEil, but narCISWithA CONь was afraid, He was above him ISOLIMONNO ALPHA-KETOGLUTARAl. SUCCINILxia COENZYMEoh, AMBERwas
FUMAROVO, APPLEI stocked up for the winter, turned around SHUKoh again.

Krebs cycle

Figure 3 – Krebs Cycle

Figure 3 Krebs cycle

The set of chemical reactions that form metabolic pathways is very diverse and large. Below in the figure, such pathways for the Krebs cycle are shown by line segments Arabidopsis thaliana – Thale cress. Thale cress is widely used as a model organism for studying plant genetics and developmental biology[5][6]. It is believed that it played the same role for plant genetics as house mouse And fruit fly to study animal genetics.

The species is widely used for research in space. In particular, it was grown on soviet stations «Salute-7“in 1982[7]. NASA planned to grow the plant on Moon in 2015[8]and the authors of the project Mars One – on Mars in 2018[9].

Figure 4 – Metabolic network of the Krebs cycle of Arabidopsis thaliana.  Enzymes and metabolites are indicated by red rectangles, and interactions between them are indicated by black lines.

Let us give some details about the processes implemented at individual stages.

Glycolysis (Greek “glykis” – sweet, “lysis” – dissolve) – an oxygen-free stage of dissimilation, an enzymatic non-hydrolytic anaerobic process of the breakdown of carbohydrates to pyruvic acid. Enzymes leading to glycolysis are located in the hyaloplasm (colloidal substance of the cytoplasm) and are not associated with membranes.

The end products of glycolysis are two molecules of pyruvic acid, two molecules of ATP and two molecules of reduced NADH.2. If further oxygen oxidation is impossible (in obligate anaerobes), pyruvic acid can be oxidized into lactic acid (in this case, one molecule of NADH will be consumed).2 for the oxidation of each molecule of pyruvic acid into lactic acid), ethyl alcohol or other fermentation products.

If further oxygen oxidation is possible, then pyruvic acid enters the mitochondria from the cytoplasm, where it undergoes oxidative decarboxylation. The acetyl-CoA (acetyl coenzyme A, acetyl coenzyme A) formed in the process then enters the Krebs cycle. Glycolysis is the evolutionarily most ancient pathway for the breakdown of glucose.

In anaerobes, it is the only process of obtaining energy. In aerobes, glycolysis necessarily precedes the oxygen stage of dissimilation or occurs under conditions of oxygen deficiency. Glycolysis is energetically significantly less advantageous. Than oxygen oxidation.

Figure 5 – Relationship between metabolic components and a fragment of metabolic pathways

Figure 5 – Connection of metabolic components and fragment of metabolic pathways

General energy balance of the organism is determined on the basis of the caloric content of the introduced nutrients and the amount of heat released, which can be measured or calculated. It should be taken into account that the caloric content obtained by laboratory calorimetry may differ from the physiological caloric value, since some substances in the organism do not burn completely, but form end products of metabolism capable of further oxidation.

This primarily applies to proteins, the nitrogen of which is excreted from the body mainly in the form of urea, which retains some potential calorie reserve. It is obvious that the caloric value, respiratory coefficient and heat generation value are different for different substances. The physiological caloric value (in kcal/g) for carbohydrates is 4.1; lipids – 9, 3; proteins – 4, 1; the heat generation value (in kcal per 1 liter of oxygen consumed) for carbohydrates is 5.05; lipids – 4, 69; proteins – 4, 49.

Conclusion

– Absolutely all cells of the body are subject to metabolism

  • Most of the energy you burn in the three main ways is produced by your resting metabolism.1. resting metabolism, or basal metabolism – energy is used for basic body functions; 2. 10% energy is used to digest food (the thermic effect of food); 3.energy from 10 to 30% is used for physical activity.

  • Metabolism varies from person to person, and scientists still don't understand why.

  • Aging slows down metabolism

  • Weight gain and weight loss are not equivalent: the body resists weight loss much more strongly than weight gain

  • Researchers do not fully understand why this phenomenon occurs.

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