Synthesis of cell ATP reserves occurs. ATP structure and biological role. Functions of ATP. Structure of fatty substances
G.N. PETRAKOVICH. Another aspect of the topic. Our eyes, if not the mirror of the soul, then their transparent environments - the pupil and the iris - are still screens for the topographical “cinema” constantly emanating from us. “Integral” holograms fly through the pupils, and in the irises protons, carrying a significant charge of kinetic energy, continuously excite the molecules in the pigment clumps. They will excite them until everything is in order in the cells that “sent” their protons to these molecules. The cells will die, something else will happen to them, to the organ - the structure in the pigment clumps will immediately change. This will be clearly recorded by experienced iridodiagnosticians: they already know exactly - from the projections in the iris - which organ is sick and even with what. Early and accurate diagnosis! Some doctors do not have a very favorable attitude towards their colleagues-iridodiagnosticians, considering them almost charlatans. In vain! Iridodiagnosis, as a simple, publicly available, cheap, easily translated into mathematical language, and most importantly, an accurate and early method for diagnosing various diseases, will be given the green light in the near future. The only drawback of the method was the lack of a theoretical basis. Its foundation is outlined above. CORRESPONDENT. I think that for our readers it would be necessary to explain the process of formation of holograms of each individual. You can do it better than me. G.N. PETRAKOVICH. Let us imagine the interactions of accelerated protons with any large bulk (three-dimensional) molecule in a cell, occurring very quickly. Such interactions with the nuclei of the target atoms that make up this large molecule will consume many protons, which, in turn, will leave a voluminous, but “negative” trace in the proton beam in the form of a vacuum, “holes.” This trace will be a real hologram, embodying and preserving part of the structure of the molecule itself that reacted with protons. A series of holograms (which happens “in nature”) will display and preserve not only the physical “appearance” of the molecule, but also the order of physical and chemical transformations of its individual parts and the entire molecule as a whole over a certain period of time. Such holograms, merging into larger three-dimensional images, can display the life cycle of an entire cell, many neighboring cells, organs and parts of the body - the entire body. There is one more consequence. Here it is. In living nature, regardless of consciousness, we communicate primarily through fields. With such communication, having entered into resonance with other fields, we risk losing, partially or completely, our individual frequency (as well as purity), and if in communication with green nature this means “dissolving in nature,” then in communication with people, especially with those who have a strong field, this means partially or completely losing their individuality - becoming a “zombie” (according to Todor Dichev). There are no technical “zombie” devices under the program and it is unlikely that they will ever be created, but the influence of one person on another in this regard is quite possible, although, from a moral point of view, it is unacceptable. When protecting yourself, you should think about this, especially when it comes to noisy collective actions, in which it is not reason or even true feeling that always prevails, but fanaticism - the sad child of malicious resonance. The flow of protons can only increase due to merging with other flows, but in no way, as opposed to, for example, an electron flow, does not mix - and then it can carry complete information about entire organs and tissues, including about such a specific organ like the brain. Apparently, we think in programs, and these holograms are capable of transmitting a stream of protons through our gaze - this is proven not only by the “expressiveness” of our gaze, but also by the fact that animals are able to assimilate our holograms. To confirm this, we can refer to the experiments of the famous trainer V.L. Durov, in which academician V. took part. M. Bekhterev. In these experiments, a special commission instantly came up with any tasks feasible for the dogs, V.L. Durov immediately handed over these tasks to the dogs with a “hypnotic gaze” (at the same time, as he said, he himself seemed to become a “dog” and mentally carried out the tasks with them), and the dogs exactly followed all the instructions of the commission. By the way, photographing hallucinations can be associated with holographic thinking and the transmission of images by a stream of protons through the gaze. A very important point: the information-carrying protons “tag” the protein molecules of their body with their energy, and each “labeled” molecule acquires its own spectrum, and by this spectrum it differs from a molecule with exactly the same chemical composition, but belonging to a “foreign” body. The principle of mismatch (or coincidence) in the spectrum of protein molecules underlies the body’s immune reactions, inflammation, as well as tissue incompatibility, which we have already mentioned. The mechanism of smell is also built on the principle of spectral analysis of molecules excited by protons. But in this case, all molecules of a substance in the air inhaled through the nose are irradiated with protons, with an instant analysis of their spectrum (the mechanism is very close to the mechanism of color perception). But there is “work” that is performed only by a high-frequency alternating electromagnetic field - this is the work of the “second” or “peripheral” heart, about which much was written at one time, but whose mechanism no one has yet discovered. This is a special topic for conversation. To be continued... Millions of biochemical reactions take place in any cell of our body. They are catalyzed by a variety of enzymes, which often require energy. Where does the cell get it? This question can be answered if we consider the structure of the ATP molecule - one of the main sources of energy.
ATP is a universal energy source
ATP stands for adenosine triphosphate, or adenosine triphosphate. The substance is one of the two most important sources of energy in any cell. The structure of ATP and its biological role are closely related. Most biochemical reactions can occur only with the participation of molecules of a substance, this is especially true. However, ATP is rarely directly involved in the reaction: for any process to occur, the energy contained precisely in adenosine triphosphate is needed.
The structure of the molecules of the substance is such that the bonds formed between phosphate groups carry a huge amount of energy. Therefore, such bonds are also called macroergic, or macroenergetic (macro=many, large amount). The term was first introduced by the scientist F. Lipman, and he also proposed using the symbol ̴ to designate them.
It is very important for the cell to maintain a constant level of adenosine triphosphate. This is especially true for muscle cells and nerve fibers, because they are the most energy-dependent and require a high content of adenosine triphosphate to perform their functions.
The structure of the ATP molecule
Adenosine triphosphate consists of three elements: ribose, adenine and residues
Ribose- a carbohydrate that belongs to the pentose group. This means that ribose contains 5 carbon atoms, which are enclosed in a cycle. Ribose connects to adenine through a β-N-glycosidic bond on the 1st carbon atom. Phosphoric acid residues on the 5th carbon atom are also added to the pentose.
Adenine is a nitrogenous base. Depending on which nitrogenous base is attached to ribose, GTP (guanosine triphosphate), TTP (thymidine triphosphate), CTP (cytidine triphosphate) and UTP (uridine triphosphate) are also distinguished. All these substances are similar in structure to adenosine triphosphate and perform approximately the same functions, but they are much less common in the cell.
Phosphoric acid residues. A maximum of three phosphoric acid residues can be attached to ribose. If there are two or only one, then the substance is called ADP (diphosphate) or AMP (monophosphate). It is between the phosphorus residues that macroenergetic bonds are concluded, after the rupture of which 40 to 60 kJ of energy is released. If two bonds are broken, 80, less often - 120 kJ of energy is released. When the bond between ribose and the phosphorus residue is broken, only 13.8 kJ is released, so there are only two high-energy bonds in the triphosphate molecule (P ̴ P ̴ P), and in the ADP molecule there is one (P ̴ P).
These are the structural features of ATP. Due to the fact that a macroenergetic bond is formed between phosphoric acid residues, the structure and functions of ATP are interconnected.
The structure of ATP and the biological role of the molecule. Additional functions of adenosine triphosphate
In addition to energy, ATP can perform many other functions in the cell. Along with other nucleotide triphosphates, triphosphate is involved in the construction of nucleic acids. In this case, ATP, GTP, TTP, CTP and UTP are suppliers of nitrogenous bases. This property is used in processes and transcription.
ATP is also necessary for the functioning of ion channels. For example, the Na-K channel pumps 3 sodium molecules out of the cell and pumps 2 potassium molecules into the cell. This ion current is needed to maintain a positive charge on the outer surface of the membrane, and only with the help of adenosine triphosphate can the channel function. The same applies to proton and calcium channels.
ATP is the precursor of the second messenger cAMP (cyclic adenosine monophosphate) - cAMP not only transmits the signal received by cell membrane receptors, but is also an allosteric effector. Allosteric effectors are substances that speed up or slow down enzymatic reactions. Thus, cyclic adenosine triphosphate inhibits the synthesis of an enzyme that catalyzes the breakdown of lactose in bacterial cells.
The adenosine triphosphate molecule itself may also be an allosteric effector. Moreover, in such processes, ADP acts as an antagonist to ATP: if triphosphate accelerates the reaction, then diphosphate inhibits it, and vice versa. These are the functions and structure of ATP.
How is ATP formed in a cell?
The functions and structure of ATP are such that the molecules of the substance are quickly used and destroyed. Therefore, triphosphate synthesis is an important process in the formation of energy in the cell.
There are three most important methods for the synthesis of adenosine triphosphate:
1. Substrate phosphorylation.
2. Oxidative phosphorylation.
3. Photophosphorylation.
Substrate phosphorylation is based on multiple reactions occurring in the cell cytoplasm. These reactions are called glycolysis - anaerobic stage. As a result of 1 cycle of glycolysis, from 1 molecule of glucose two molecules are synthesized, which are then used to produce energy, and two ATP are also synthesized.
- C 6 H 12 O 6 + 2ADP + 2Pn --> 2C 3 H 4 O 3 + 2ATP + 4H.
Cell respiration
Oxidative phosphorylation is the formation of adenosine triphosphate by transferring electrons along the membrane electron transport chain. As a result of this transfer, a proton gradient is formed on one side of the membrane and, with the help of the protein integral set of ATP synthase, molecules are built. The process takes place on the mitochondrial membrane.
The sequence of stages of glycolysis and oxidative phosphorylation in mitochondria constitutes a common process called respiration. After a complete cycle, 36 ATP molecules are formed from 1 glucose molecule in the cell.
Photophosphorylation
The process of photophosphorylation is the same as oxidative phosphorylation with only one difference: photophosphorylation reactions occur in the chloroplasts of the cell under the influence of light. ATP is produced during the light stage of photosynthesis, the main energy production process in green plants, algae and some bacteria.
During photosynthesis, electrons pass through the same electron transport chain, resulting in the formation of a proton gradient. The concentration of protons on one side of the membrane is the source of ATP synthesis. The assembly of molecules is carried out by the enzyme ATP synthase.
The average cell contains 0.04% adenosine triphosphate by weight. However, the highest value is observed in muscle cells: 0.2-0.5%.
There are about 1 billion ATP molecules in a cell.
Each molecule lives no more than 1 minute.
One molecule of adenosine triphosphate is renewed 2000-3000 times a day.
In total, the human body synthesizes 40 kg of adenosine triphosphate per day, and at any given time the ATP reserve is 250 g.
Conclusion
The structure of ATP and the biological role of its molecules are closely related. The substance plays a key role in life processes, because the high-energy bonds between phosphate residues contain a huge amount of energy. Adenosine triphosphate performs many functions in the cell, and therefore it is important to maintain a constant concentration of the substance. Decay and synthesis occur at high speed, since the energy of bonds is constantly used in biochemical reactions. This is an essential substance for any cell in the body. That's probably all that can be said about the structure of ATP.
metabolites glycolysis (1,3-diphosphoglycerate,phosphoenolpyruvate),
metabolites tricarboxylic acid cycle (succinyl-CoA) And
creatine phosphate.
The main way ATP is produced in a cell is oxidative phosphorylation , occurring in the structures of the inner membrane of mitochondria. At the same time, the energy of the hydrogen atoms of the NADH and FADH 2 molecules formed in glycolysis, the TCA cycle, and the oxidation of fatty acids, during redox processes converted into ATP bond energy.
However, there is also another way to phosphorylate ADP to ATP - substrate phosphorylation . This method is associated with transfer of energy from high-energy communication any substance (substrate) on ADP. Such substances include:
Pyruvate is oxidized to acetyl-CoA.
Pyruvic acid (PC, pyruvate) is a product of the oxidation of glucose and some amino acids. Its fate varies depending on the availability of oxygen in the cell. IN anaerobic conditions it is restored to lactic acid . IN aerobic conditions, pyruvate symports with H + ions moving along the proton gradient and penetrates into mitochondria. Here it is converted into acetyl-coenzyme A ( acetyl-CoA ) by using pyruvate dehydrogenase multienzyme complex.
Pyruvate dehydrogenase multienzyme complex
Summary equation for the oxidation of pyruvic acid
Pyruvate dehydrogenase multienzyme complex located in the matrix of eukaryotic mitochondria. In humans, it consists of 96 subunits , organized into three functional proteins. Gigantic formation, has 50 nm in diameter, which is Five times!!! more than ribosome .
The process is underway five sequential reactions in which 5 coenzymes take part:
Pyruvate dehydrogenase (E 1, PC dehydrogenase), serves as a coenzyme thiamine diphosphate(TDP), catalyzes the 1st reaction.
Dihydrolipoyl transacetylase (in Russian-language literature there are names - Dihydrolipoate acetyltransferase And lipoamide reductase transacetylase(E 2), coenzyme - lipoic acid, catalyzes the 2nd and 3rd reactions.
Dihydrolipoyl dehydrogenase (dihydrolipoate dehydrogenase)(E 3), coenzyme – FAD, catalyzes the 4th and 5th reactions.
In addition to the indicated coenzymes, which are firmly associated with the corresponding enzymes, the complex takes part in coenzyme A And ABOVE.
The essence of the first three reactions boils down to the decarboxylation of pyruvate (catalyzed by pyruvate dehydrogenase, E 1), the oxidation of pyruvate to acetyl and the transfer of acetyl to coenzyme A (catalyzed by dihydrolipoyl transacetylase, E 2).
Acetyl-sCoA synthesis reactions
The remaining 2 reactions are necessary for the oxidation of dihydrolipoate back to lipoate with the formation of FADH 2 and the reduction of NADH (catalyzed by dihydrolipoyl dehydrogenase, E 3).
Reactions of nadn formation Regulation of the pyruvate dehydrogenase complex
The regulated enzyme of the PVK dehydrogenase complex is the first enzyme - pyruvate dehydrogenase(E 1). This is achieved by two auxiliary enzymes - kinase And phosphatase, providing her phosphorylation And dephosphorylation.
Kinase activated by excess biological oxidation end product ATP and products of the PVK-dehydrogenase complex – NADH And acetyl-CoA. Active kinase phosphorylates pyruvate dehydrogenase and inactivates it.
Enzyme phosphatase , activated by ions calcium or hormone insulin, dephosphorylates and activates pyruvate dehydrogenase.
The role of ATP in the life of the body as a whole is difficult to overestimate. Among the most important consumers of ATP, the following should be noted:
1. Most anabolic reactions ( anabolic reactions ) pass through cells using ATP, i.e.:
Synthesis of proteins from amino acids,
Synthesis of DNA and RNA from nucleotides,
Synthesis of polysaccharides,
Fat synthesis
2. ATP is necessary for active transmembrane transport of molecules and ions,
for induction and conduction of nerve impulses ( nerve impulses),
maintaining cellular volume through osmotic mechanisms ( osmosis),
for muscle contractions ( muscle contraction),
for the implementation of bioluminescence in tissues ( bioluminescence).
3.ATP is a synaptic transmitter, widespread in various
nal organs, especially in the presynaptic endings of effector neurons. When these endings are stimulated, purine breakdown products, adenosine and inosine, are released. In evolutionary biology, it is generally believed that ATP was the only mediator common to all organisms at the early stages of evolution. In the process of evolution, due to the increasing complexity of the structure of organisms, new specialized synaptic mediators began to appear. Studies on individual organs of experimental animals have shown that ATP promotes relaxation of smooth muscles of the digestive organs
Energy consumption disorders in the heart: causes and consequences
One of the most important channels of energy consumption in the human body is the activity of the heart. Continuous heart function (C) requires steady and reliable energy consumption. Blockage of one of the arteries that feed the C itself stops the blood supply to a section of the heart muscle and tissue ischemia occurs. A prolonged period of ischemia leads to the death of cardiac muscle cells and cardiomyocytes - then myocardial infarction develops. But, if the vascular spasm was short-lived, and the blood flow in it is restored, then the contractile work of the myocardium can be completely restored. This problem has become especially important in connection with the development of heart transplant technology. How is energy supplied to cardiac muscle cells and how is it used?
Fig. 45 Main energy-consuming structures of the cardiomyocyte.
Regulation of the contractile function of cardiomyocytes occurs through calcium ions. They enter the cell from the outside and cause the release of calcium ions contained in the cisterns of the sarcoplasmic reticulum. These ions bind to myofibrils and cause their contraction.
The main consumer of ATP in cardiomyocytes is the contractile apparatus of myofibrils (Fig. 45); its energy requirement is estimated to be about 80% of total energy expenditure. Approximately 10-15% of energy is spent on maintaining the transmembrane potential and excitability of cardiomyocytes. And about 5% of the cell's energy is used for synthetic processes. In addition to ATP, another high-energy compound, creatine phosphate (CP), which is more efficiently used by the cell than ATP, can be a source of energy in cells.
The process of energy formation in cardiomyocytes is disrupted for various reasons. With sudden myocardial ischemia, ATP synthesis in mitochondria stops, and the content of Kf and ATP quickly decreases. In this case, the functions of the contractile apparatus are most deeply disrupted.
Protective mechanisms during ischemia.
During the development of ischemia in the heart muscle, protective mechanisms are included that reduce destructive processes.
1. ATP-dependent potassium channels open (Fig. 46). Normally they are closed, but if ATP re-synthesis is insufficient, they open and potassium actively leaves the cells. This is accompanied by a decrease in membrane potential and cell excitability.
Fig.46. Metabolic consequences of myocardial ischemia
2. Acidification of the cytoplasm of cells occurs - acidosis develops. The cessation of oxidation in mitochondria during ischemia leads to the activation of glycolysis, the accumulation of under-oxidized products,
an increase in the concentration of hydrogen ions and a pH shift.
3. The breakdown of ATP and Kf is accompanied by the accumulation of phosphate in the heart cells. This reduces the sensitivity of contractile proteins to Ca +2 ions.
4. The accumulation of adenosine as a result of ATP breakdown blocks adenoceptors on cardiomyocytes. As a result, the neurotransmitter norepinephrine does not activate heart cells and prevents a decrease in ATP and Kp reserves.
Thus, already at the beginning of the ischemia stage, several protective mechanisms are activated, reducing the entry of calcium ions into cardiomyocytes and the sensitivity of the contractile apparatus to the action of calcium ions. During ischemia, the level of contractile function drops very quickly (within 30 seconds) to approximately 5-10% of the initial level, while the content of AVTP and Kf decreases moderately. This allows the heart cells to expend energy economically and survive an unfavorable period. With prolonged ischemia (several hours), energy deficiency worsens, acidosis intensifies - this leads to the destruction of cellular organelles and cell necrosis.
A sudden suppression of ATP synthesis during ischemia could cause the death of cardiomyocytes within a few minutes if the natural protective mechanisms in the heart did not work. They quickly suppress contractile activity and ensure economical expenditure of energy reserves for tens of minutes. Elimination of the causes of ischemia during this period can restore the contractility of cardiomyocytes and heart function.
The ischemic zone can be reduced by administering adenosine, potassium ions, and nitric oxide NO, which has a vasodilating effect. It turned out that it is nitric oxide that mediates the action of many vasodilators, such as nitroglycerin.
Cell nucleus
The term “nucleus” was coined by Brown in 1833, when he first described permanent spherical structures in plant cells. Later, the same structures were discovered in all cells of higher organisms, including humans.
The cell nucleus, usually one in a cell, consists of nuclear envelope, separating it from the cytoplasm, chromatin, nucleolus, nuclear protein matrix(framework) and karyoplasma(nuclear juice) (Fig. 27 Chentsov).
Granular endoplasmic reticulum Nuclear time
ribosomes
Fig.47. Cell nucleus
These nuclear components are present in all eukaryotic cells - unicellular and multicellular.
Core(nucleus) cell - a structure containing genetic information about the cell and the whole organism. The nucleus carries out two groups of general functions: 1- storage of genetic information, 2- its implementation in the form of protein synthesis.
1. The storage and maintenance of hereditary information in the form of an unchanged DNA structure is associated with the work of the so-called. repair enzymes that eliminate spontaneously occurring damage to DNA molecules. Repair enzymes also work in cells damaged by radiation, promoting more or less effective recovery of cells from radiation damage. This type of reparation was discovered by the famous Obninsk radiobiologist Prof. Archer N.V. in the 70s of the 20th century.
2. Another side of the activity of the nucleus is the work of the protein synthesis apparatus. Ribosomal components are also synthesized in the nucleus. From the general scheme of protein synthesis (Figure 16 Chentsov) it is clear that the source of information for the start of biosynthesis is DNA
Structure and chemical composition of the cell nucleus
The vast majority of cells of higher mammals contain only one nucleus, although there are also multinucleated cells - for example, muscle fiber cells - myosymplasts.
Nuclear chromatin is a dense substance that fills almost the entire volume of the nucleus. In non-dividing (interphase) cells it is diffusely distributed throughout the volume of the nucleus; in dividing cells it becomes denser (condenses) and forms dense structures - chromosomes. Chromatin stains well with basic dyes , That’s why it got its name (from the Greek chroma – color, paint). Chromatin contains DNA in complex with proteins – histone (alkaline) and non-histone. Diffuse chromatin of interphase nuclei is called by geneticists euchromatin, condensed chromatin – heterochromatin. In both forms, chromatin consists of fibrils 20-25 nm thick.
It is known that the length of individual DNA molecules can reach hundreds of microns and even approach a centimeter. In the human chromosome set, the longest chromosome is the first, up to 4 cm long. Chromosomes have many places of independent replication (duplication) - replicons. Thus, DNA is a chain of tandemly arranged replicons of varying sizes.
Chromatin proteins make up 60-70% of its dry weight. Histones (alkaline proteins) are not evenly distributed along the DNA molecule, but in the form of blocks, each of them contains eight histone molecules, forming the structure nucleosome. The process of nucleosome formation is accompanied by DNA supercoiling and shortening its length by approximately 7 times.
In addition to DNA, the nucleus also contains messenger RNA molecules associated with proteins.
Chromosome cycle
It is well known that female and male reproductive cells carry a single set of chromosomes and therefore contain 2 times less DNA than other cells of the body. Sex cells with a single set of chromosomes are called haploid. Ploidity, i.e. multiplicity, is designated in genetics by the letter n. Thus, cells with a set of 1n are haploid, with 2n are diploid, and with 3n are triploid. Accordingly, the amount of DNA in a cell (denoted by the letter c) depends on its ploidy: cells with a 2n number of chromosomes contain a 2c amount of DNA. During fertilization, two haploid cells merge, each of which carries a set of 1n chromosomes, therefore forming diploid(2n,2c) cell is a zygote. Then, due to the division of the diploid zygote and the subsequent division of diploid cells, an organism will develop whose cells will be diploid, and some of them (sexual) will again be haploid.
However, the process of division of diploid cells is preceded by a phase of DNA synthesis-reduplication, i.e. Cells appear with the amount of DNA equal to 4c, their number of chromosomes is 4 n. And only after the division of such a tetraploid (4c) cell, two new diploid cells appear.
It is difficult to see chromosomes in the nuclei of interphase (resting) cells. They appear in the nucleus shortly before cell division. In interphase, however, doubling and reduplication of chromosomes occur. During this period, DNA synthesis occurs, which is why it is called the synthetic, or S-period. During this period, an amount of DNA greater than 2c is detected in the cells. After the end of the S-period, the amount of DNA in the cell is 4c (complete doubling of chromosomal material). If you count the number of chromosomes in prophase, then there will be 2n, but this is a false impression, because at this time, each chromosome is double (as a result of reduplication). At this stage, a pair of chromosomes is in close contact with each other, they twist around each other. Consequently, already at the beginning of prophase, chromosomes consist of two sister chromosomes - chromatids. They remain connected to each other in the next phase - metaphase, when the chromosomes line up in the equatorial plane of the cell. In the next stage, anaphase, pairs of homologous chromosomes diverge to opposite poles of the cell, after which the cell divides. Then, in telophase, the diverged diploid sets (2n) of chromosomes begin to decondense, i.e. loosen. This is how one chromosomal cycle ends and the next one begins (Fig. 31 Chentsov). The chromosome (cellular) cycle in multicellular eukaryotes lasts 1-1.5 days.
Nucleolus (Nucleolus)
In the nucleus of all eukaryotic cells one or more round-shaped bodies are visible - nucleoli. They stain well with basic dyes because they are rich in RNA. The nucleolus is a derivative of chromosomes, while it is an independent organelle whose function is to form ribosomal RNA and ribosomes. The nucleolus is heterogeneous in structure - the central part is fibrillar, where ribosome precursors are concentrated, and the periphery is granular, where maturing ribosomal subunits are concentrated.
Nuclear envelope (karyolemma)
It is a structure that bounds the cell nucleus. It separates the two intracellular components from each other - the nucleus from the cytoplasm. The significance of this separation of structures in space is important: it creates additional (in comparison with prokaryotes) opportunities for the regulation of gene activity during the synthesis of specific proteins.
The nuclear envelope consists of two membranes - outer and inner, between which the perinuclear space is located (Fig. 106 Chentsov). In general terms, the nuclear envelope can be represented as a two-layer bag that separates the contents of the nucleus from the cytoplasm. However, the nuclear envelope has a characteristic feature that distinguishes it from other membrane structures of the cell - these are special nuclear pores formed by the fusion of two nuclear membranes.
The outer membrane of the nuclear envelope belongs to the membrane system of the endoplasmic reticulum - numerous polyribosomes are located on it, and the nuclear membrane itself passes into the reticulum membranes. The inner membrane of the nuclear envelope does not have ribosomes on its surface. However, it is associated with chromatin and this is a characteristic feature of the inner nuclear membrane.
Another function of the nuclear membrane is the creation of intranuclear order, architecture, and fixation of chromosomal material in three-dimensional space.
Nuclear pores are the result of the fusion of two nuclear membranes. The pore openings are about 90 nm in diameter. The nuclear pore complex, which includes 8 peripheral protein granules and one central one, is involved in the transport of protein and nucleoprotein molecules and in the recognition of these molecules. This transport process is active and requires ATP. On average, there are several thousand pore complexes per core (Fig. 109 Chentz).
Nuclear protein matrix
The processes of replication (doubling) and transcription (reading information) of chromatin are carried out in the nucleus in a strictly ordered manner. To implement these processes, there is an intranuclear system that unites all nuclear components - chromatin, nucleolus, nuclear envelope. This structure is the nuclear protein framework, or matrix (NPM). At the same time, it does not represent a clear morphological structure. According to the morphological composition, the nuclear membrane consists of three components: a reticulated protein layer - the lamina, an internal network - the skeleton, and a “residual” nucleolus. The main component of the structures of nuclear membranes are fibrillar proteins, similar in amino acid composition to intermediate microfilaments.
The role of the nuclear envelope in nuclear-cytoplasmic exchange.
The nuclear envelope serves as a regulator in nuclear-cytoplasmic exchange. The exchange of products between the nucleus and the cytoplasm is very large: all nuclear proteins enter the nucleus from the cytoplasm, and all RNA is removed from the nucleus. Nuclear pore complexes in this process serve not only as a transport mechanism (translocator), but also as a sorter of transferred material. Through the pores, ions, sugars, nucleotides, ATP and hormones enter the nucleus by passive transport. Using the method of passive transport, high-molecular compounds with a mass of no more than 5.10 3 Da penetrate through the nuclear membrane in both directions. Active transport of macromolecules in both directions occurs through nuclear pores.
Non-membrane organelles.
Ribosomes. These specialized cell organelles ensure the synthesis of proteins and polypeptides. They are present in all types of animal cells and are high-molecular ribonucleoproteins. Ribosomes (R) contain proteins and a special type of RNA called ribosomal RNA (rRNA). Dimension P – 20 x 20 x 20 nm. Consists of large and small subunits. Each of the subunits is formed from a ribonucleoprotein strand. Cells contain individual Ps and their complexes - polyribosomes. They can be freely located in the hyaloplasm or associated with the membranes of the endoplasmic reticulum. Typically, free P is contained in unspecialized and fast-growing cells, while those associated with the reticulum are found in specialized cells. In addition, free P synthesize protein for the cell’s own needs, and bound protein for export.
Rice. “Bunches” of ribosomes
Cytoskeleton. This is the musculoskeletal system in the cell, creating a truly cellular skeleton (Fig). The system contains protein filamentous formations. The filamentous and fibrillar structures of the cytoskeleton are dynamic formations that appear and disappear depending on the functional state of the cell. The main components of the cytoskeleton are: microtubules and microfilaments.
Using immunofluorescence methods, it was established that microfilaments include contractile proteins - actin, myosin, tropomyosin. That is, microfilaments are nothing more than the contractile apparatus of the cell, ensuring the mobility of both the cell itself and the organelles inside it. Microfilaments have a thickness of 5-7 nm.
Microtubules take part in the creation of temporary (division spindle, cytoskeleton of interphase cells) and permanent structures (centrioles, cilia, flagella). They are straight, non-branching hollow cylinders with a diameter of 24 nm, the thickness of the cylinder wall is 5 nm. In an electron microscope, a cross section of microtubules reveals 13 subunits of the tubulin protein.
Cellular center (centrosome). Consists of centrioles and associated microtubules. Using electron microscopy methods, it was possible to study the fine structure of centrioles. The basis of this structure is made up of 9 triplets of microtubules, forming a hollow cylinder (Fig). Its width is about 2 nm, length – 3-5 nm.
Typically, in interphase cells there are two centrioles, forming a single structure - a diplosome. In it, the centrioles are located at right angles to each other. Of the two centrioles, a mother and a daughter centriole are distinguished. The end of the daughter centriole is directed towards the surface of the mother centriole.
In preparation for mitotic division, the cell doubles its centrioles. Interestingly, the increase in the number of centrioles is not associated with their division, budding or fragmentation, but is the result of the formation of a primordium next to the original centriole.
Before mitosis, centrioles serve as the center for the formation of the microtubule spindle.
In addition to the named structures, some cells include cilia and flagella, which are outgrowths of the cytoplasm. Inside these processes there is a complex contractile system of microtubules and contractile proteins such as tubulin and dynein. Cells carry out movement with the help of cilia and flagella.
Lecture 5. Integral cell reactions
The whole variety of transformations of substances in cells consists of chains of biochemical reactions. To carry out biochemical reactions, it is necessary for substances to enter the cell - endocytosis, transformation of substances in the cell - metabolism, and the removal of metabolic end products in the form of unnecessary waste or biologically active substances necessary for the body - exocytosis.
Endocytosis. There are several ways to implement endocytosis:
Transmembrane passive and active transport of substances into the cell. This form of endocytosis is described in the corresponding chapter.
Pinocytosis is the uptake of liquid colloidal particles by a cell.
Phagocytosis is the capture by a cell of dense and large corpuscular particles up to the capture of other cells.
In general, the entry of solid or liquid substances into a cell from the outside is called the general term heterophagy. This process is important for the human body in such organs and systems as protective (phagocytic activity of blood neutrophils, macrophages), changes in bone tissue (osteoclasts), formation of the hormone thyroxine in the follicles of the thyroid gland, reabsorption of protein and other macromolecules in the tubules of the nephron of the kidneys.
Cellular metabolism, or metabolism, is a set of processes of biosynthesis of complex biological molecules from simpler ones (assimilation) and reactions of breakdown of complex macromolecules with the release of thermal energy used by cells for various purposes (dissimilation).
The cell effectively uses the energy contained in the chemical bonds of proteins, carbohydrates and fats supplied with food, and released during their breakdown (hydrolysis) in the digestive tract. That is, cellular metabolism is carried out according to the rules of the first law of thermodynamics - energy is neither created nor destroyed, it passes from one type to another, suitable for doing work.
Schematically, the processes of dissimilation of nutrients occur in such a way that at the initial stage in the digestive tract they are broken down into monomers (proteins into amino acids, fats into fatty acids, carbohydrates into monosaccharides), after which, regardless of the nature of the nutrients, further
Exocytosis. The removal of substances from cells is also carried out using several mechanisms. Just like endocytosis, active and passive transport of substances from the cell takes place. Active transport removes ions and small molecules, passive transport removes most inorganic substances and end products of metabolism (so-called waste products).
Another method of removal is available for removing large molecular compounds from cells. They accumulate in the cytoplasm in the Golgi apparatus in the form of transport vesicles and, with the help of a system of microtubules, are concentrated at the plasma membrane of the cell. The vesicle membrane is embedded in the plasma membrane, and the contents of the vesicle are transported outside the cell. Fusion of the vesicle with the plasmalemma can occur without any additional signals - this is called exocytosis constitutive. In this way, as a rule, the products of the cell’s own metabolism, or waste, are eliminated. But a significant part of the cells synthesizes special substances necessary for the body to function - secrets. In order for the secretion vesicle to merge with the plasmalemma, a signal from the outside is necessary. This exocytosis is called adjustable. Signaling molecules that stimulate the excretion of secretions are called liberins, and those that inhibit excretion are called statins. This method of exocytosis is very common in the neuro-endocrine system during the production of hormones and neurotransmitters.
Intercellular interactions
Cell functions
Cell reproduction. Cell cycle.
According to one of the postulates of cell theory, cell reproduction, i.e. an increase in their number occurs through division of the original cell. This rule is true for both eukaryotic and prokaryotic cells. The lifespan of a cell as such, from division to the next division, or from division to its death, is called cell cycle . In the body, cells of different tissues and organs have different abilities to divide. For example, in all organs there are cell populations that have completely lost the ability to divide. These are specialized, or differentiated, cells. They perform, as a rule, special functions inherent only to this type of cell and are part of the parenchyma of organs.
But the body also contains constantly renewing tissues – epithelial and hematopoietic tissues. In such tissues there is a fairly large proportion of actively dividing cells that replace obsolete ones. The cycle duration is usually 10-30 hours in actively dividing cell populations. Dividing cells have different amounts of DNA depending on the stage of the cell cycle. This is typical for both germ and somatic cells. It is known that male and female germ cells carry a single (haploid) set of chromosomes and contain half as much DNA as somatic diploid cells of the whole organism. Ploidy in genetics is denoted by the letter n . Thus, germ cells carry a 1n set, somatic cells have a 2n set, i.e. They are diploid, there are cells with a set of chromosomes 3n - this is a triploid set.
During the cell cycle, a population of diploid cells contains both diploid and tetraploid sets of chromosomes and intermediate amounts of DNA during the period of cell rest (interphase). This heterogeneity is due to the fact that the doubling of the amount of DNA occurs before the start of division (mitosis).
All cell cycle(animation on the Internet) consists of four time periods: mitosis proper (M), presynthetic (G 1), synthetic (S) and postsynthetic (G 2) periods of interphase.
In the G 1 period, which follows immediately after mitosis, cells have a diploid DNA content (2c; c is the DNA content corresponding to ploidy). During this period, cell growth begins due to the accumulation of cellular proteins and the cell prepares for the synthetic period. It is during this period that the synthesis of enzymes is activated,
necessary for the formation of DNA precursors. The energy demand in the cell increases sharply.
In the S-period, the amount of DNA doubles (reduplication) and the number of chromosomes doubles (1n--- 2n). In different cells in the S-period, different amounts of DNA can be found - from 2 s to 4 s. During this period, the RNA content increases in accordance with the amount of DNA.
The post-synthetic phase of G 2 is also called pre-mitotic. During this period, the synthesis of messenger RNA necessary for mitosis is activated.
At the end of this period, before mitosis, RNA synthesis decreases.
In the growing tissues of animals and plants there are a number of cells that are, as it were, outside the cell cycle. These cells are called cells of the G 0 period, or resting. They do not enter the next stage -G 1 after mitosis, but stop dividing. At the same time, they do not differentiate, remaining in a state ready for mitosis. For example, most liver cells are in the G 0 period - they do not synthesize DNA and do not divide. However, after removal of part of the liver, as has been shown experimentally in animals, most of the liver cells enter the mitotic cycle. Many cells completely lose the ability to return to the mitotic cycle - for example, neurons in the brain.
Cell cycle and radiosensitivity
It is interesting to note that different stages of the cell cycle differ significantly in their sensitivity to external influences. For example, the G 1 period and mitosis itself are most sensitive to chemical agents and physical influences, such as ionizing radiation, while the main part of the interphase (G 2 and S periods) is less sensitive. Experimental studies on cell cultures obtained from irradiated animals have shown that differences in radiosensitivity can reach 40-fold or more between stages of the cell cycle. In addition, the time parameters of individual stages of the cycle change in irradiated cells; for example, there is a delay in the onset of the mitotic stage and an extension of the G 2 stage.
In radiation cytology, phenomena of spontaneous restoration of the vital activity of irradiated cells from potentially lethal damage are known. This effect was discovered by Russian researcher V.I. Korogodin in the 50s of the 20th century and was essential for assessing the true radiosensitivity of cells and the body as a whole.
Cell division: mitosis.
Mitosis (karyokinesis, indirect division) is a universal method of dividing any eukaryotic cells (animated film on the Internet). Already synthesized in the previous pre-mitotic period, 2 chromosomes (double set - 4n) transform into a condensed compact form, a spindle of division in the cell is formed and homologous chromosomes diverge to the opposite poles of the cell, after which the cytoplasm of the cell is divided (cytokinesis, cytotomy).
The process of mitosis is conventionally divided into several main phases: prophase, metaphase, anaphase, telophase.(rice)
Prophase. As already noted, at the end of the S-period in the interphase nucleus of the cell, the amount of DNA is 4 s, since doubling of the chromosomal material has already occurred. However, morphologically in a light microscope, the number of chromosomes in prophase differs as 2n, although each of them has already doubled. However, by the end of prophase, the duality of the chromosome set is already morphologically distinguishable due to the actively ongoing process of chromosome condensation (compaction). The number of chromosomes 4n exactly corresponds to the amount of DNA - 4 s.
prophase
prometaphase
telophase
metaphase
anaphase
Rice. Mitosis
In prophase, the level of synthetic processes in the cell significantly decreases, and a fission spindle is formed - an apparatus for diluting genetic material to the two poles of the cell.
Metaphase. This phase takes up about a third of the total time of mitosis. Its distinctive feature is that at this time the formation of the spindle ends and the chromosomes line up at the equator of the spindle in the middle of the cell. The cell in this phase has a characteristic appearance called the “metaphase plate,” or mother star. By the end of metaphase, doubled and condensed chromosomes are already clearly visible in a light microscope in the form of sister chromatids closely adjacent to each other. Their arms are parallel to each other, but there is already a separation space between the chromatids.
Anaphase. The homologous chromosomes lined up in the center of the cell lose contact with each other and synchronously begin to diverge to the opposite poles of the cell that has not yet divided. This is the shortest phase of mitosis. However, important events occur at this time: the separation of two identical sets of chromosomes and their movement to the two poles of the cell.
Telophase. Two sets of chromosomes (2nx 2) form two cell nuclei; At the same time, the process of dividing the original cell into two daughter cells occurs—cytokinesis, cytotomy. In the submembrane layer of the cytoplasm, contractile proteins such as actin fibrils are located, oriented in the equator zone of the cell. These proteins carry out the “constriction” of the cell in the center and its division into two daughter cells. Mitosis ends.
If the mitotic apparatus is damaged, mitosis may be delayed in metaphase or even chromosome scattering may occur. In addition, multipolar and asymmetric mitoses may occur. When cytotomy processes are disrupted, giant nuclei or multinucleated cells are formed. Such effects are observed during malignant transformation of cells both under the influence of external sources (chemical agents, drugs, ionizing and non-ionizing radiation, viruses) and under the influence of internal factors (for example, some hormones, biological active substances).
Meiosis
In addition to the mitotic division of somatic cells, which occurs in all organs and tissues of the body, there is a special, unique form of cell reproduction, leading to the formation of germ cells with a haploid set of chromosomes. This form is called meiosis and it occurs in higher animals (and humans) and higher plants in the primary generative organs. In humans, the formation of sex cells (gametes) occurs in the testicles (in men) and ovaries (in women).
The formation of male germ cells (spermatogenesis) occurs in the tissue of the convoluted seminiferous tubules of the testicles and includes 4 successive stages: reproduction, growth, maturation and formation (Fig).
Initial phase of spermatogenesis – reproduction spermatogenic epithelium and the formation of more mature cells - spermatogonia. Among the spermatogonia there is a pool of stem cells, which are the source of the formation of new cells, and another part of the spermatogonia continues further maturation, or differentiation.
The result of this maturation (phase growth) is the loss of the cell's ability to divide, the formation of a cell called a primary spermatocyte, or 1st order spermatocyte. During this period, the 1st order spermatocyte increases in volume and enters the stage of the first meiotic division (reduction division). This stage is long and consists of 5 stages: leptotene, zygotene, pachytene, diplotene and diakinesis. After division, each of the two daughter cells, called 2nd order spermatocytes, or secondary spermatocytes, already contains a haploid number of chromosomes (23 in humans).
The next phase is the second division (phase maturation), occurring as normal mitosis in secondary spermatocytes without reduplication (doubling) of chromosomes. As a result, four cells with a haploid chromosome set - spermatids - are formed from two secondary spermatocytes. Thus, each initial spermatogonia gives rise to 4 spermatids, which have a haploid (single) set of chromosomes.
The spermatids no longer divide and, after complex morphological changes, become mature spermatozoa. This transformation occurs in the final stage of spermatogenesis - the phase formation sperm.
Spermatogonia (diploid cell)
mitosis
Additional spermatogonia
Primary spermatocyte
First meiotic division
Secondary spermatocyte
Second meiotic division
Spermatids (haploid cells)
Sperm
Head
Neck
Tail
Rice. Spermatogenesis
The process of spermatogenesis in humans lasts about 75 days and occurs in waves along the convoluted seminiferous tubule. In a certain section of the tubule there is a certain set of spermatogenic epithelial cells.
Lecture 6. Cell reactions to external influences.
The cells of the body are constantly exposed to various environmental factors - chemical, physical and biological, as well as internal influences - nervous and neuro-humoral. These factors cause primary disturbances in cellular structures, which usually results in a functional disorder in an organ or system. The fate of cells depends on the intensity of exposure, its nature and duration. After disturbances, cells can adapt, adapt to the influencing factor, recover after canceling the damaging effect, or irreversible changes will ultimately lead to cell death.
With reversible damage, cells respond with a number of functional and morphological changes. One of the most common criteria for cellular damage is a change in the ability of cells to interact with various dyes. Normal cells absorb dyes dissolved in water and deposit them as granules in the cytoplasm; the core is not stained. Damaged cells (from heating, changes in pressure, pH of the environment, exposure to a denaturing agent) lose this ability and the paint is diffusely distributed not only in the cytoplasm, but also in the nucleus. In the case of reversible damage, provided that the action of the external factor is canceled, granule formation in the cytoplasm of cells is restored.
Another characteristic sign of cell damage is a decrease in respiratory processes in the cell, while oxidative phosphorylation, necessary for the synthesis of ATP, decreases significantly. Damaged cells are characterized by increased glycolytic processes (acidification), a drop in the amount of ATP and activation of proteolysis (denaturation of proteins). The entire set of nonspecific reversible changes in cells that occur under the influence of various agents is called “paranecrosis”. In this initial and reversible stage of change, the processes of cellular assimilation and dissimilation are not significantly altered.
However, in the event of irreversible damage to cellular metabolism, events unfold that affect not only the cytoplasm, but also the nuclear apparatus. The most significant manifestation of irreversible changes in a damaged cell is condensation (compaction, aggregation) of chromatin, a decline in nuclear synthetic processes. When a cell dies, chromatin forms rough clumps inside the nucleus (pyknosis), and the nucleus itself falls apart or even dissolves (karyorrhexis).
In damaged cells, mitotic activity sharply decreases and cells are delayed at different stages of mitosis. The permeability of cell membranes is disrupted, resulting in vacuolization of membrane organelles of the cell. At the same time, there is an intensive accumulation in the cell of some individual products of disturbed metabolism. In general pathology, such changes in cell structure are called dystrophies. So, for example, in case of fatty degeneration, fatty inclusions accumulate in the cells, in case of carbohydrate degeneration - glycogen, in case of protein degeneration - the deposition of protein granules, pigments, etc. The final stage of irreversible changes in cells is their death, at the tissue and organ level this manifests itself in the form necrosis, or death of tissue (organ).
A special form of disturbances in the regulation of cell metabolism is a violation of cell differentiation, most often leading to the development tumor process. Tumor cells are characterized by uncontrolled reproduction, autonomous behavior in the body and disruption of intercellular interactions. All these properties of tumor cells are preserved from generation to generation, i.e. are heritable. Due to these features, cancer cells are considered mutants from the point of view of the insubordination of their behavior to the regulatory influences of the body.
Here, the molecular processes of maintaining and regulating ion homeostasis of cells under normal conditions and during malignant transformation play an important role. Concept cell ion homeostasis(IGC) includes a system for regulating the activity of ions, which ensure a normal intracellular environment, and water. The most important ions for the life of a cell include K + , Na + , Ca 2+ , H + , PO 2- , and ions of such energy-intensive molecules as ATP and ADP (adenosine diphosphate). IGC can control cell behavior by changing, first of all, the quantitative relationships between the main systems of the cell - for example, the intensity of protein and RNA synthesis, the mass of the cytoplasm and nucleus, etc. In the event of a disruption in the functioning of IGCs in cells, first of all, the molecular mechanisms of their interactions with each other change, as a result of which tumor cells acquire autonomous behavior and low sensitivity to regulatory influences (Malenkov A.G., 1976).
Cell death.
There are two forms of cell death – necrosis And apoptosis.
Necrosis caused predominantly by various external factors that directly or indirectly affect membrane permeability and cellular metabolism. In all cases, a chain of morpho-functional disorders occurs, ultimately leading to cell dissolution - lysis.
So, necrosis is a form of cell death characterized by:
functional - irreversible cessation of their vital functions,
morphologically – violation of membrane integrity, changes in the nucleus (pyknosis, karyorrhexis, lysis), cytoplasm (edema), cell destruction, inflammatory reaction,
biochemically - impaired energy production, coagulation and hydrolytic breakdown of proteins, nucleic acids, lipids,
genetically – loss of genetic information. (Lushnikov E.F., Abrosimov A.Yu., 2001).
Apoptosis is a process of cell death that can occur without a primary disruption of cellular metabolism. More often called apoptosis programmed cell death; This refers to the fact that this form of cell death actually develops according to a program embedded in the genetic apparatus of the cells. At the same time, as a result of the action of various stimuli on the cell, certain genes are activated in the nucleus, stimulating the self-destruction of the cell. The self-destruction program can be implemented under the influence of certain signaling molecules of the body itself - for example, hormones or protein molecules. Thus, lymphocytes that multiply in huge quantities in the thymus gland (thymus) almost all die within a few hours without leaving the thymus gland and in the bloodstream under the influence of glucocorticoids - hormones of the adrenal cortex. The meaning of this phenomenon is completely unclear, but nevertheless it occurs precisely along the path of apoptosis.
The activation of self-destruction genes can be caused by the cessation of some regulatory signal. For example, after removal of the testes, prostate cells in men completely die.
Cell death, as if for no apparent reason, often occurs during normal embryonic development of the body. For example, cells in a tadpole's tail die as a result of the activation of thyroid hormones at a certain stage of the tadpole's development. In the adult body, mammary gland cells undergo apoptosis during its involution (reverse development).
Fig. Stages of apoptosis development. The photo on the left is a normal cell;
In the center is the beginning of cytoplasm fragmentation; on the right is the final stage
fragmentation of the cytoplasm and nucleus.
The process of apoptosis is significantly different from necrosis. This form of cell death is characterized by:
functional – irreversible cessation of cell activity,
morphologically - loss of microvilli and intercellular contacts, condensation of chromatin and cytoplasm, cell shrinkage, formation of vesicles from plasma membranes, cell fragmentation and formation of micronuclei,
biochemically - hydrolysis of cytoplasmic proteins and DNA breakdown,
genetically - structural and functional restructuring of the genetic apparatus, culminating in the absorption of cellular fragments by tissue macrophages without an inflammatory reaction (Lushnikov E.F., Abrosimov A.Yu., 2001).
The essence of apoptosis, its place in normal and pathological conditions.
In a multicellular organism, cell death occurs constantly, but in different tissues and organs it is observed under certain conditions. The biological nature of cell death is ambiguous. The most important and significant thing is that apoptosis has different meanings for the normal life of vertebrate animals and invertebrate animals (and now it has become known that for the plant world):
in embryogenesis, apoptosis is an element of development and is associated with the formation of tissues and organs,
when an organism exists independently, apoptosis is an integral part of metamorphosis (in insects and amphibians),
in animals, the processes of histogenesis and organogenesis occur with the participation of apoptosis,
in a mature organism, apoptosis is part of the homeostatic mechanism of cell replacement,
During aging, apoptosis reflects natural cell death.
Reproductive cell death.
Depending on the stages of the cell cycle, there are two forms of cell death from external influences. One of them is reproductive death, which affects only dividing cell populations. This form of cell death was discovered in radiobiological experiments on laboratory animals in the 70s.
In irradiated animals, cytological studies revealed that some cells lost the ability to divide after going through several cell cycles, followed by death. Moreover, this form of death is also observed in cells in in vitro culture.
Interphase cell death.
Another phenomenon, also discovered in radiobiological studies, is immediate cell death after irradiation, without division - in interphase. This form of cell damage is characteristic of radiation effects in the hematopoietic system in the bone marrow, in the immune and nervous systems. According to modern concepts, interphase cell death occurs along the path of apoptosis.
Lecture 7. General embryology. Basic concepts and phenomena.
Embryology(from the Greek embryon - embryo) - the science of the patterns of development of embryos. Medical embryology (E) studies the patterns of development of the human embryo, the causes of the development of deformities and other deviations from the norm, possible ways and methods of influencing embryogenesis (the process of embryo formation).
Currently, medical technologies make it possible in many cases to combat infertility, carry out the birth of “test tube” children, and carry out transplantations of embryonic organs and tissues. Methods for in vitro cultivation of eggs, extra-organism fertilization and implantation of the embryo into the uterus have now been developed.
The process of human embryonic development has undergone a long evolution and largely reflects the stages of development of other representatives of the animal world. Therefore, the early stages of development of the human embryo are similar to similar stages of embryogenesis of less organized chordates.
The human reproductive system includes several interconnected stages in the development of male and female reproductive cells, the fusion of these cells during fertilization, and the formation of a new organism from the embryo. These steps are as follows:
Progenesis – development and maturation of germ cells - eggs and sperm. As a result of progenesis, a haploid (single) set of chromosomes appears in mature germ cells, and structures are formed that facilitate their mutual fusion (fertilization) and the development of a new organism.
Embryogenesis- part of human ontogenesis (his individual development), includes the main stages: 1 - fertilization with the formation of a zygote, 2 - fragmentation of the zygote and the formation of a blastula (blastocyst), 3 - gastrulation - the formation of germ layers and a complex of axial organs, 4 - the formation of embryonic and extraembryonic tissues and organs, 5 - formation of organ systems (systemogenesis).
Post-embryonic period – the functioning of a new individual after birth outside the mother’s body, including the continued formation of organs and tissues after birth.
Progenesis.
Sex cells (gametes), unlike somatic cells, contain not a double, but a single set of chromosomes. In humans, this double set is 46 chromosomes, therefore gametes contain 23 chromosomes.
Fig.Diploid chromosome set (46 chromosomes) in human somatic cells
All chromosomes in gametes are called autosomes there are 22 of them in the gamete , with the exception of one - the twenty-third, which is called sex chromosome. IN men's sex cells half of the gametes (sperm) WITH) contains a sex chromosome with female genetic material (X chromosome), and half a chromosome with male genetic material – Y chromosome. In female gametes (eggs) ) (I) all sex chromosomes are X-bearing. A characteristic feature of gametes is their low level of metabolism. In addition, mature gametes lose the ability to divide.
Male reproductive cells - sperm - are formed in huge quantities in most higher animals. In mammals and humans, sperm are formed and mature during the entire active sexual period in the generative organs - the testes, from the primary germ cells of the spermatogenic epithelium of the convoluted tubules. During the process of mitotic division, part of the spermatogonia (the next stage of differentiation of primary germ cells) enters the process of differentiation to the state of mature sperm, and part does not differentiate and continues to divide mitotically, thereby maintaining a pool of stem (original) cells. (Next you need to briefly describe meiosis. )
The mechanism of ATP synthesis during glycolysis is relatively simple and can be easily reproduced in vitro. However, it has never been possible to simulate respiratory ATP synthesis in the laboratory. In 1961, the English biochemist Peter Mitchell suggested that enzymes - neighbors in the respiratory chain - observe not only a strict order of reactions, but also a clear order in the space of the cell. The respiratory chain, without changing its order, is fixed in the inner shell (membrane) of the mitochondria and “stitches” it several times as if with stitches. Attempts to reproduce the respiratory synthesis of ATP failed because the role of the membrane was underestimated by researchers. But the reaction also involves enzymes concentrated in mushroom-shaped growths on the inner side of the membrane. If these growths are removed, then ATP will not be synthesized.
Oxidative phosphorylation, the synthesis of ATP from adenosine diphosphate and inorganic phosphate, which occurs in living cells due to the energy released during the oxidation of organic matter. substances in the process of cellular respiration. In general, oxidative phosphorylation and its place in metabolism can be represented by the following diagram:
AN2 - organic substances oxidized into the respiratory chain (the so-called substrates of oxidation, or respiration), ADP-adenosine diphosphate, P-inorganic phosphate.
Since ATP is necessary for the implementation of many processes that require energy (biosynthesis, mechanical work, transport of substances, etc.), oxidative phosphorylation plays a critical role in the life of aerobic organisms. The formation of ATP in the cell also occurs due to other processes, for example, during glycolysis and various types of fermentation. proceeding without the participation of oxygen. Their contribution to ATP synthesis under conditions of aerobic respiration is a small part of the contribution of oxidative phosphorylation (about 5%).
In animals, plants and fungi, oxidative phosphorylation occurs in specialized subcellular structures—mitochondria (Fig. 1); In bacteria, the enzyme systems that carry out this process are located in the cell membrane.
Mitochondria are surrounded by a protein-phospholipid membrane. Inside the mitochondria (in the so-called matrix), a number of metabolic processes of breakdown of nutrients take place, supplying substrates for the oxidation of AN2 for oxidative phosphorylation Naib. important of these processes are the tricarboxylic acid cycle and the so-called. -oxidation of fatty acids (oxidative breakdown of a fatty acid with the formation of acetyl-coenzyme A and an acid containing 2 less C atoms than the original; the newly formed fatty acid can also undergo -oxidation). The intermediates of these processes undergo dehydrogenation (oxidation) with the participation of dehydrogenase enzymes; the electrons are then passed on to the mitochondrial respiratory chain, an ensemble of redox enzymes embedded in the inner mitochondrial membrane. The respiratory chain carries out a multi-stage exergonic transfer of electrons (accompanied by a decrease in free energy) from substrates to oxygen, and the released energy is used by the ATP synthetase enzyme located in the same membrane to phosphorylate ADP to ATP. In an intact (undamaged) mitochondrial membrane, electron transfer in the respiratory chain and phosphorylation are closely coupled. For example, turning off phosphorylation upon depletion of ADP or inorganic phosphate is accompanied by inhibition of respiration (respiratory control effect). A large number of effects that damage the mitochondrial membrane disrupt the coupling between oxidation and phosphorylation, allowing electron transfer to occur even in the absence of ATP synthesis (uncoupling effect).
The mechanism of oxidative phosphorylation can be represented by the diagram: Electron transfer (respiration) A ~ B ATP A ~ B is a high-energy intermediate. It was assumed that A ~ B is a chemical compound with a high-energy bond, for example, a phosphorylated enzyme of the respiratory chain (chemical coupling hypothesis), or a strained conformation of any protein involved in oxidative phosphorylation (conformational coupling hypothesis). However, these hypotheses have not received experimental confirmation. The most widely recognized is the chemiosmotic concept of conjugation, proposed in 1961 by P. Mitchell (he was awarded the Nobel Prize in 1979 for the development of this concept). According to this theory, the free energy of electron transport in the respiratory chain is spent on the transfer of H+ ions from mitochondria through the mitochondrial membrane to its outer side (Fig. 2, process 1). As a result, an electric difference occurs on the membrane. potentials and chemical difference. activity of H+ ions (pH inside mitochondria is higher than outside). In total, these components give the transmembrane difference in the electrochemical potential of hydrogen ions between the mitochondrial matrix and the external aqueous phase, separated by a membrane:
where R is the universal gas constant, T is the absolute temperature, F is the Faraday number. The value is usually about 0.25 V, with the main part (0.15-0.20 V) represented by the electrical component. The energy released when protons move inside mitochondria along the electric field towards their lower concentration (Fig. 2, process 2) is used by ATP synthetase to synthesize ATP. Thus, the oxidative phosphorylation scheme, according to this concept, can be represented in the following form:
Electron transfer (respiration) ATP
The coupling of oxidation and phosphorylation through makes it possible to explain why oxidative phosphorylation, in contrast to glycolytic (“substrate”) phosphorylation occurring in solution, is possible only in closed membrane structures, and also why all effects that reduce electrical resistance and increase proton conductivity of the membrane suppress (“uncouple”) oxidative phosphorylation. Energy, in addition to ATP synthesis, can be directly used by the cell for other purposes - transport of metabolites, movement (in bacteria), restoration of nicotinamide coenzymes, etc.
There are several sections in the respiratory chain that are characterized by a significant difference in the redox potential and are associated with energy storage (generation). There are usually three such sites, called points or conjugation points: NADH: ubiquinone reductase unit (0.35-0.4 V), ubiquinol: cytochrome c reductase unit (~ ~ 0.25 V) and cytochrome c- oxidase complex (~ 0.6 V) - coupling points 1, 2 and 3, respectively. (Fig. 3). Each of the interface points of the respiratory chain can be isolated from the membrane in the form of an individual enzyme complex with redox activity. Such a complex, embedded in a phospholipid membrane, can function as a proton pump.
Typically, to characterize the efficiency of oxidative phosphorylation, the H+/2e or q/2e values are used, indicating how many protons (or electrical charges) are transferred across the membrane during the transport of a pair of electrons through a given section of the respiratory chain, as well as the H+/ATP ratio, indicating how many protons must be transferred from outside to inside mitochondria through ATP synthetase to synthesize 1 ATP molecule. The value of q/2e for interface points is 1, 2 and 3, respectively. 3-4, 2 and 4. The H+/ATP value during ATP synthesis inside mitochondria is 2; however, another H+ can be spent on the removal of synthesized ATP4- from the matrix into the cytoplasm by the adenine nucleotide transporter in exchange for ADP-3. Therefore, the apparent value of H+ / ATPext is 3.
In the body, oxidative phosphorylation is suppressed by many toxic substances, which, according to the place of their action, can be divided into three groups: 1) respiratory chain inhibitors, or so-called respiratory poisons. 2) ATP synthetase inhibitors. The most common inhibitors of this class used in laboratory studies are the antibiotic oligomycin and the protein carboxyl group modifier dicyclohexylcarbodiimide. 3) So-called uncouplers of oxidative phosphorylation They do not suppress either electron transfer or ADP phosphorylation itself, but have the ability to reduce the value on the membrane, due to which the energy coupling between respiration and ATP synthesis is disrupted. The uncoupling effect is exhibited by a large number of compounds with a wide variety of chemical structures. Classic uncouplers are substances with weak acidic properties that can penetrate the membrane in both ionized (deprotonated) and neutral (protonated) forms. Such substances include, for example, 1-(2-dicyanomethylene)hydrazino-4-trifluoro-methoxybenzene, or carbonyl cyanide-n-trifluoromethoxy-phenylhydrazone, and 2,4-dinitrophenol (formulas I and II, respectively; protonated and deprotonated forms are shown) .
Moving through the membrane in an electric field in ionized form, the disconnector reduces; returning back to the protonated state, the uncoupler decreases (Fig. 4). Thus, this “shuttle” type of action of the disconnector leads to a decrease
Ionophores (for example, gramicidin) that increase the electrical conductivity of the membrane as a result of the formation of ion channels or substances that destroy the membrane (for example, detergents) also have an uncoupling effect.
Oxidative phosphorylation was discovered by V. A. Engelhardt in 1930 while working with avian erythrocytes. In 1939, V. A. Belitser and E. T. Tsybakova showed that oxidative phosphorylation is associated with electron transfer during respiration; G. M. Kalkar came to the same conclusion somewhat later.
Mechanism of ATP synthesis. The diffusion of protons back through the inner membrane of the mitochondrion is coupled with the synthesis of ATP using the ATPase complex, called the coupling factor F,. On electron microscopic images, these factors appear as globular mushroom-shaped formations on the inner membrane of mitochondria, with their “heads” protruding into the matrix. F1 is a water-soluble protein consisting of 9 subunits of five different types. The protein is an ATPase and is associated with the membrane through another protein complex F0, which laces the membrane. F0 does not exhibit catalytic activity, but serves as a channel for the transport of H+ ions across the membrane to Fx.
The mechanism of ATP synthesis in the Fi~F0 complex is not fully understood. There are a number of hypotheses on this matter.
One of the hypotheses explaining the formation of ATP through the so-called direct mechanism was proposed by Mitchell.
According to this scheme, at the first stage of phosphorylation, the phosphate ion and ADP bind to the g component of the enzyme complex (A). Protons move through the channel in the F0 component and combine in the phosphate with one of the oxygen atoms, which is removed as a water molecule (B). The oxygen atom of ADP combines with a phosphorus atom to form ATP, after which the ATP molecule is separated from the enzyme (B).
For the indirect mechanism, various options are possible. ADP and inorganic phosphate are added to the active site of the enzyme without an influx of free energy. H + ions, moving along the proton channel along the gradient of their electrochemical potential, bind in certain areas of Fb causing conformational changes. changes in the enzyme (P. Boyer), as a result of which ATP is synthesized from ADP and Pi. The release of protons into the matrix is accompanied by the return of the ATP synthetase complex to its original conformational state and the release of ATP.
When energized, F1 functions as an ATP synthetase. In the absence of coupling between the electrochemical potential of H+ ions and ATP synthesis, the energy released as a result of the reverse transport of H+ ions in the matrix can be converted into heat. Sometimes this is beneficial, since increasing the temperature in the cells activates the enzymes.
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