General Catabolism Scheme of Nutrients in the Body. Catabolism phases, the energy effect of individual phases. General and specific catabolism paths. General principles of regulation of metabolism paths Basic principles of the organization of metabolism Power converge
The result of the design should be the table, correctly and effectively represent objects and their relationships.
Relational database is considered correct (agreed) and effective If it has the following characteristics:
1) no redundancy;
2) consistency preventing data loss;
3) minimal use of null values.
Scheme of relational base The data is called a set of relationship headers included in the database, and their connections. The scheme contains structural and semantic information.
Some single consolidated table, which presents all the necessary data on the subject area, called universal attitude (general or global table).
Such a general table can be very ineffective due to two main developments: redundancy and inconsistencies. (Yes, null values \u200b\u200b...
…)
The use of a universal relationship containing redundant data can generate three problems of inconsistency, called anomalies : Insertion anomalies (inclusion), delete and update (modifications).
The process of ordering, the structuring of the submitted data is called normalization.
Disadvantages of the Global Table (built on all occasions):
- rigidity;
- unreliability (potential contradiability);
- increased consumption of resources;
- bulkiness (redundancy).
Under the rigidity is a mandatory modification of the table itself when the task is changed.
Redundancy- the need to store full information, for example, the name of the company in each product record.
Potential contradiability- the need to change the value of the attribute in all records, in case of programming error, is expensive.
Anomaly inclusion- Cannot be records about the supplier, if he did not put a single product.
Anomaly removal- When removing all goods supplied by the supplier, its address and others are lost.
Normalization- This is a design process that allows you to guarantee the effectiveness of data structures in the relational database. When designing, data is divided into several related tables, in compliance with the special requirements of normalization.
Normalization - Practically, this is a splitting table into two or more, which have the best properties when you turn on, change and delete data. The ultimate goal of normalization is reduced to obtaining such a database project in which each fact appears only in one place.. The redundancy of information is excluded. This is done not so much in order to save memory, how much to eliminate possible contradictions (inconsistencies) of stored data.
The basis of the process of normalization is the formal apparatus, called E. Codud, as part of the relational theory, called normalization of relationships.
It should be noted that the normalization process is not related to the physical placement of data. We are talking only about user and global logical data presentation.
The process of normalization is based on the concept functional dependency Attributes.
Definition of functional dependence (FZ).
BUTtribut AT Tables functionally dependent on the attribute BUT the same table in that and only when at any given time for each of the different attribute values BUT Be sure to exist only one of the different attribute values. AT. Note that attributes BUT and AT may be single and composite.
Statement that ATfunctionally depends on BUTmeans the same thing as BUT Definitely determines AT, t. e. If at some point in time it is known BUTthen you can get and value AT.
Functional dependence is indicated by the arrow BUT ® AT.
The concept of FZ is similar to the concept of function in mathematics and reflects the semantic (semantic) relationship of the corresponding attributes of the essence.
Distinguish the following types of functional dependencies: Complete, partial and transitive FZ.
If the uniform attribute depends on the entire compound key and does not depend on its parts, then they indicate the full functional dependence of the attribute from the composite key.
If the uniform attribute depends only on the part of the composite key, they indicate a partial functional dependence of the attribute from the composite key.
If the attribute is depends on the attribute A, and depends on the attribute B, but there is no inverse dependence, they say that the attribute C depends on and transitively.
Some FZ reflects the relationships in the subject area under study, others can be generated by the structure of illiterately formed relationships (tables). With incorrectly grouped relationships, some FZ may be undesirable due to the indicated abnormalities that they cause when the database (updating) is called.
Lecture 7. Definitions and characteristics of normal forms 1NF, 2NF, 3NF, BCNF. The concept and types of denormalization.
Definition . The relationship is in 1NF if any values \u200b\u200bof all attributes are atomic and no repetitive groups.
Obviously, if an arbitrary ratio meets the requirements of the relational model, it consistent with the definition of 1NF accordingly.
Definition . The relationship is in 2NF if it corresponds to 1NF and its non-selection attributes fully dependfrom the entire primary key.
Definition . The ratio is in 3NF if it corresponds to 2NF and does not contain transitive dependencies.
Definition . The attitude is in BCNF if it corresponds to 3nf and if only if any functional dependence between its fields is reduced to a full functional dependence on the possible key.
Lecture 8. CASE-TECHNOLOGY DB Design. Design using the Entity-Communication method.
General Principles of Catabolism Organization in the Organization
The source of free energy in the organisms of heterotrophs is the disintegration of nutrients, in other words, the catabolic processes occurring in cells and tissues. Catabolism includes hundreds of chemical reactions, dozens of metabolic paths. At the same time, a certain logic is traced in the organization of catabolic processes.
All catabolism of nutrients in the body can be divided into three stages or, as they call, three phases. In the first phase, the polymer molecules on the monomers occurs: proteins are split up to amino acids, oligo and polysaccharides on monosaccharides and their derivatives, lipids for higher fatty acids, glycerol, aminospirts, etc. It should be noted that it is not only about splitting food components in the gastrointestinal The path, but also the decay of biopolymers directly in cells. In this phase there are no oxidative processes, hydrolysis and phosphorus are dominated. Energy release does not exceed 12% of its total content in nutrients, and all the energy is dissipated in the form of heat.
However, in this phase, one important event occurs a sharp decrease in the number of compounds that then come into the second phase of catabolism. Thus, with a variety of food products, millions of various proteins come to the gastrointestinal tract and all of them are split up to 2025 monomeric acids, and several hundred different lipids when splitting give a one and a half of various higher fatty acids and alcohols; Several hundreds of different oligosaccharides and polysaccharides are given during decay, in turn, one and a half dozen monosaccharides and their derivatives. Thus, instead of millions of different compounds entering the first phase, about 50 compounds are formed at the output.
In the second phase, these five dozen compounds are subjected to further cleavage, so that at the exit of this phase there are only five compounds: acetylcoa, succinylco, fumarate, oxaloacetate and 2 oxoglutate. Thus, continuing in the second phase, the splitting of nutrients is accompanied by an even greater unification of intermediate products. Catabolic processes going in the second phase are mixed, because It also goes phosphorusis, and liaise splitting, and thiolism and oxidative reactions. In the second phase, it is allocated to 1/3 of the entire power in nutrients, and part of it is accumulated. In this phase of catabolism, all nitrogen-containing finite catabasem products are formed, as well as part of CO2 and H2O.
The internal logic of such an organization of catabolic processes is that with the deepening of the decay of nutrients, the number of intermediate metabolic products decreases. This principle of building catabolic processes was called the principle of convergence.
The metabolic pathways of the first and second phase of catabolism is usually individual for individual compounds or groups related to the structure of substances of the same class. Therefore, the metabolic pathways of the first and second phase of catabolism received the name of the specific paths of catabolism. At the same time, the metabolic processes of the third phase of catabolism are the same, regardless of which connection is split. In this regard, the metabolic pathways of the third phase received the name of commonaties of catabolism.
The presence of common metabolic pathways in the third phase of catabolism, in which 2/3 of all free energy is distinguished, increases the adaptive capabilities of living organisms, because It makes it relatively easy to switch from one type of nutrient to another. The presence of general metabolic pathways in the third phase also makes it possible to reduce the number of different enzymes needed by cells and tissues for the processing of different nutrients. All this helps organisms in the struggle for survival and is the result of a long evolution of living organisms.
When studying metabolic processes, we first and look at the metabolic pathways of the third phase of catabolism: the cycle of Krebs tricarboxylic acids and the chain of respiratory enzymes.
The source of free E in the organisms of heterotrophs is disintegration of nutrientsIn other words, catabolic processes occurring in cells and tissues. Catabolism includes hundreds of chemicals. Reactions, dozens of metabolic paths. At the same time, a certain logic is traced in the organization of catabolic processes. All catabolism Pete. substances in the body can be divided into three stages or, as they call, three phases.
In the first phase The polymer molecules on the monomers are cleavage: proteins are split up to amino acids, oligo and polysaccharides on monosaccharides and their derivatives, lipids for higher fatty acids, glycerol, amino alcohol, etc. In this phase there are no oxidative processes, hydrolysis and phosphorus are dominated. All energy dissipates in the form of heat. In this phase, a sharp decrease in the number of compounds, which then come to the second phase of catabolism occurs. Thus, millions of various proteins come with a variety of food products in the gastrointestinal tract and all of them are split up to 20-25 ac.
In the second phase These five dozen compounds are subjected to further cleavage, so that at the outlet of this phase there are only five compounds: acetylcoa, succinylco, fumarate, acetate and 2 oxogllutarate. Thus, continuing in the second phase, the splitting of nutrients is accompanied by an even greater unification of intermediate products. Catabolic processes going in the second phase are mixed, because It also goes phosphorusis, and liaise splitting, and thiolism and oxidative reactions. In this phase of catabolism, all nitrogen-containing finite catabasem products are formed, as well as part of CO2 and H2O. The organization of catabolic processes is that with the deepening of the decay of nutrients, the number of metabolic products decreases. This principle of building catabolic processes was called the principle of convergence. The metabolic pathways of the first and second phase of catabolism is usually individual for individual compounds or groups related to the structure of substances of the same class. Therefore, the metabolic pathways of the first and second phase of catabolism received the name of the specific paths of catabolism. At the same time, the metabolic processes of the third phase of catabolism are the same, regardless of which connection is split.
In this regard, the metabolic pathways third Phase They got the name of common catabolic pathways. The presence of common metabolic pathways in the third phase of catabolism, in which 2/3 of all free energy is distinguished, increases the adaptive capabilities of living organisms, because It makes it relatively easy to switch from one type of nutrient to another. The presence of general metabolic pathways in the third phase also makes it possible to reduce the number of different enzymes needed by cells and tissues for the processing of different nutrients. All this helps organisms in the struggle for survival and is the result of a long evolution of living organisms. Putting the third phase of catabolism: the cycle of tricarboxylic acids Krebs and the chain of respiratory enzymes
Option 1
1. Write the thermodynamics equation, reflecting the relationship between changes in free energy (G) and the total energy of the system (E). Answer:
2. Indicate which two types of cell energy can use to perform work. Answer : The cell for performing work can use or the energy of chemical bonds of macroehers, or the energy of transmembrane electrochemical gradients.
3. Specify the amount of free energy released by breaking 1 praying of thioether bonds in the compounds of the type of acyl-economy under standard conditions . Answer : 8.0 kcal / m.
4. Specify the value of the caloric coefficient for fats. Answer : 9.3 kcal / g.
5. Specify what is called "basic exchange". Answer : Level energy consumption for pretending the body.
6. Specify what is equal to the level of "basic exchange" for a person of the average mass, expressed in kcal / day. Answer: Approximately 1800 to cal.
7. Call 5 ways to break chemical bonds in the compounds most widely represented in biological systems. Answer: Hydrolysis, phosphorus, thioliz, lipase splitting, oxidation.
8. Name the three main class of compounds coming from the first phase of catabolism to the second phase. Answer: Monosaccharides, higher fatty acids, amino acids.
9. Indicate which method of cleavage of chemical bonds dominates in the third phase of catabolism. Answer : Oxidation.
10. Equality, which means the term "convergent principle of the Catabolism Organization" in the body. Answer :
11. Explain what advantages gives a person a converged principle of the organization of catabolism in its body. Answer:
12.Napitiate using the structural formulas of metabolites, the reaction of the oxidation of isocitrate in the Krebs cycle with the indication of all the connections participating in the reaction. Answer
13. Indicate how the direction of the flow of metabolites in the cycle of tricarboxylic acids is monitored .Answer: Thermodynamic control - due to the inclusion in the metabolic path of two reactions, accompanied by a large loss of free energy.
14. Specify 2 possible ways to replenish the pool of intermediate metabolites Crex cycle. Answer: a) entering them from the second phase of catabolism, b) the reaction of carboxylation of pyruvate.
15. Here, in which cell structure the chains of the respiratory enzymes are localized. Answer : In the inner membrane mitochondria.
16. Handwood the scheme describing the functioning of intermediate carriers of electrons included in the IV complex temperature chain. Answer:
17. Give the definition of the term "oxidative phosphorylation". Answer : Synthesis of ATP with the use of energy released in the process of biological oxidation
18. Specify what role protein f | interheomocosal phosphorylation in the chains of respiratory enzymes by Mitchell. Answer : ProteinF. | Due to protons moving through an electrochemical grudite, catalyzes the formation of ATP NZ ADP and inorganic phosphate.
19. Specify what is the mechanism of the action of compounds that cause disassemble the oxidation and phosphorylation of fluctuations. Answer : These compounds act as proton carriers through the mitochondrial inner membrane bypassing the ATP synthesis system.
20. For 2 possible causes of the development of hypoxic hypoenergetic states. Answer : 2 of any variant of 4 possible: a) oxygen deficiency in the external environment; b) disorder of the respiratory organs; c) circulatory disorder; D) Violation of the ability of hemoglobin blood tolerate oxygen.
21.Reate 2 examples of compounds, in the neutralization of which the microsomal system is involved. Answer : 2 of any example of aromatic carbocycles (anthracene, benzanttracene, naftacienne, 3,4-benzpins, methyl choleantrene).
22. Apply the mechanism of protective action of antioxidants of the type of vitamin E or carotene. Answer : These compounds are made by an excess electron with a superoxide anion radical, forming a less reactive structure due to the redistribution of the electron density according to the system of conjugate double bonds available in their structure.
Option 2.
1. Explain why for chemical processes occurring in cells, the change in the enthalpy of system (H) is almost equal to the change in the total energy of the system (E).
Answer: In biologically, there are no changes in temperature or pressure during chemical reactions..
2. Indicate which chemical reactions from the point of view of thermodynamics can go spontaneously. Answer : Only exeheric chemical reactions can go spontaneously.
3. Bring 2 examples of macroeergic compounds from thioether class. Answer: Two any specific acyl-koa
Answer: 10.3 kcal / m.
5. Indicate which changes are taking place with nutrients in the first phase of catabolism. Answer : Splitting polymers for monomers.
6. Indicate which part of the total nutrient energy is released in the second phase of kataoolyism. Answer : 1/3 of all energy.
7. Indicate which finite exchange products are formed in the third phase of catabolism. Answer : Water, carbon dioxide.
8. Write a general scheme of monooxygenase reactions going in cells. Answer: Sh2 + O.2 + Kon 2 -\u003eS-Oh.+ Co-oxidized + H 2
Answer:
10.The Using the structural formulas of metabolites, the oxidation reaction of the succinate in the Krex cycle with the indication of all the connections participating in the reaction. Answer:
11. Write the total cycle equation of Krebs tricarboxylic cycles. Answer: Acetyl CoA + Signal + + Fad + Gdf ~ F + 2N: O-\u003e CO 2 - Sign + H + + Fadn 2 + GTF
12. For 2 compounds, which are altogether solid activators of the regulatory enzymes of the Krebs cycle. Answer: Adf.AM.F..
13. Let the determination of the metabolic path known as the "main chain of the respiratory enzymes of mitochondria". Answer: Metabolic path, providing protons and electron transition +H. 2 Oxygen.
14. Name intermediate carriers of the main respiratory chain capable of accepting hydrogen atoms or electrons from external sources. Answer: KoQ., cytochroms.
15. Indicate which amount of free energy is allocated under standard conditions when oxidizing 1 mol of NAD / H "by forming 1 mol H 2 O. Answer : -52,6 kcal / m.
16. Explain what is called disagreement of oxidation and phosphorylation. Answer: Violation of the relationship between the processes of oxidation and phosphorylation with the transformation of the released free energy into heat.
17. Explain the meaning of the term "hypernergetic state". Answer: Lack of energy in the cell.
18. Name 2 cytochrome participating in oxidative processes localized in the membranes of the endoplasmic network. Answer: Cytochromeb.5, cytochromeP. 450 .
19. Do you drive the circuit of the electron carriers with the participation of cytochrome P 450, functioning in the membrane bendoplasmatic network. Answer: Fuck You
20. Name 2 compounds in the biosynthesis of which a microsomal oxidation system is involved. Answer: Adrenaline (Noradrenalin). Steroid hormones.
21. For 2 possible sources of formation of peroxide anion radical in tissues. Answer :
Option 3.
1. Give an explanation to the term "free energy system". Answer: Free energy is part of the overall energy of the system, at the expense of which you can do work.
2. Indicate why endargonic reactions can not go spontaneously Answer : For the flow of endorgonic reactions, an external energy source is required.
3. Specify the amount of free energy released at a break of I pyrophosphate bonds of ATP under standard conditions. Answer : 7.3 kcal / mol.
4. Specify the amount of free energy released when the macroergic binding of 1 mole of creatine phosphate under standard conditions. Answer: 10.3 kcal / m.
5. Specify the amount of person's daily need in proteins, expressed in g / kg body weight (WHO standard). Answer : 1 g / kg.
6. Specify the value of the caloric coefficient for proteins when splitting in the human body Answer : 4.1 kcal / g.
7. Indicate which part of the common human energy consumption is covered by splitting proteins. Answer: 15%.
8. Give the definition of the concept of "catabolism". Answer : A combination of nutrient cleavage processes in the body.
9. Explain why the metabolic pathways of the first and second phases of catabolism are called specific pathamicattabolism. Answer: In these phases of catabolism, each compound or a group of related compounds is disintegrated using various metabolic paths.
10. Explain that means the term "convergent principle of the Catabolism Organization" in the body. Answer: As the flushing of nutrients deepends, the number of intermediate products decreases.
11. Explain what advantages gives a person a convergent principle of the organization of catabolism in breathering. Answer : but). The ease of transition from one type of nutrient to another. b). Reducing the number of enzymes at the final stage of catabolism.
12. For 5 signs, according to which the oxidation processes that go in biological objects and oxidation processes in the abiogenic medium are distinguished. Answer: a) "soft" conditions in which the process is underway, b) the participation of enzymes, c) oxidation is mainly by dehydrogenation, d) the process of multi-stage, e) the intensity of the process is regulated in answercell needs in energy.
13.The Using the structural formulas of metabolites, the total reaction of the conversion of 2-oxoglutarata. In Sukcinyl-CoA, indicating all the compounds participating in the reaction Answer :
14. Name 2 reactions that are points of thermodynamic control of the direction of flow of metabolites in the cyclebrus. Answer : a) Citrantsintaz reaction b) 2-oxoglutarate-dehydrogenase reaction.
15. For 3 compounds, in the structure of which the energy is accumulated, released during the oxidation of acetyl residues in the Krebs cycle. Answer : Nadn + H +, Fadn 2, GTF.
16. Name 2 intermediate calculators of hydrogen atoms supplying protons and electrons into the chain of respiratory enzymes. Answer: Nadn + H +, Fadn 2
17. Image the scheme describing the functioning of intermediate carriers of protons and electrons included in 1 complex of the main respiratory chain. Answer :
18. Bring the formula by which you can calculate the amount of released energy during the transfer of electrons, if the values \u200b\u200bof the redox potentials of the initial and final points of the electron transfer circuit are known. Answer : G." = - n. H.F. x E ".
19. These are the essence of the second stage of the conversion of the energy released in the chain of the respiratory enzymes, into the energy of the macroeergic ties of ATP within the framework of the chemoosmotic concept of the conjugation proposed by Mitchell. Answer : The energy of a transmembrane proton electrochemical gradient is used For the formation of macroeergic and communications.
20. Give 3 examples of the compound that disobey the processes of oxidation and phosphorylation in mitochondria. Answer : Polychlorophenols, polynitrophenols, acetylsalicylic acid.
21. Here, what method of oxidation of the compounds is implemented mainly during the processes of microsalkilation. Answer : Oxygenation.
22. Call 3 microsomal oxidation functions. Answer : a) Participation in catabolism of various compounds. b) participation in the biosynthesis of the required organism of compounds, c) detoxification.
23. For 3 possible methods of inactivation of superoxide anion radical. Answer : a) The return of the excess electron on cytochrome S. b) return of an excess electron to the antioxidant compound (such as vitamin E, carotene, etc.) c) inactivation during a superoxiddismutaz reaction.
24. For 2 possible sources of formation of peroxide anion radical in tissues. Answer: a) Forms in the respondents of aerobic dehydrogenation b) is formed in a superoxiddismutase reaction.
25. For 3 possible methods of inactivating peroxide anion radical in cells. Answer : a) during the reaction catalase catalase, b) during the reaction catalyzed by glutathioneer peroxidase. c) during the reaction catalyzed by peroxidase
26. Here, what role the processes of microsomal oxidation in chemical carcinogenesis can be played. Answer: In the course of neutralization of polycyclic aromatic hydrocarbons, their epoxides are formed with mutagenic activity.
Option 4.
1. Bring the equation describing I the law of thermodynamics in the form, accepting the thermodynamics of living objects Answer: ΔInsthemny + ΔEndons \u003d 0.
2. Explain what is called the energy pairing of chemical reactions. Answer: The use of free energy released during an exeergonic reaction for the implementation of an endorgonic reaction.
3. Specify the type of macroergic chemical bond in the compounds of the class of polyphosphates of nucleoside. Answer: Phosphoanhydride or pyrophosphate communication.
4. Indicate what is the level of human daily energy costs employed by mental labor. Answer : 2500 - 3000 kcal / day.
5. Indicate which part of the total nutrient energy is released in the first phase of catabolism. Answer: until 3%.
6. Indicate which 5 methods of breaking chemical bonds of nutrients are used in the second phase of catabolism. Answer : hydrolysis, phosphoroliz, thioliz, liaise splitting, oxidation.
7. Indicate 3 compounds in the macroergic links of which the energy released in the third phase of catabolism is accumulated. Answer : ATP, GTF, Succinyl-CoA.
8. Write a common diagram of reactionsArobnogride. Answer: Sh 2.+ O2 -\u003eS.oxidized +.H.2 O.2
9. Write using structural formalmetabolites, the reaction of the oxidation of the Malat of the Krex cycle with the indication of all participating in the neo-union. Answer:
10. Here, due to the action of which two main factors, the intensity of the flow of metabolites in the Krebs cycle is carried out. Answer: a) Changes in the activity of regulatory enzymes b) concentration of oxaluacetate and acetyl-cola.
11. Name the enzymes of the Krebs cycle, the activity of which is oppressed by the alto-model mechanism of high concentric ATP. Answer: Citrantsintase, IsocitrateTehydrogenase.
12. Name the compound, which is the final electron acceptor in the chain of the respiratory enzymes. Answer : Oxygen.
13. Handwood the scheme describing the functioning of intermediate carriers of electrons included in the composition of the III complex radiation circuit. Answer:
14. Specify the value of the difference between the redox potentials between the beginning and the end of the main respiratory chain. Answer: 1, 14V.
15. Here, the essence of the first stage of the conversion of the energy released in the chain of the respiratory enzymes, into the energy of macroergic ties of ATP as part of the chemiosotic concept
mitchell conjugation, Answer: The free energy released during the operation of the chain of the respiratory enzymes is used to form a proton electrochemical gradient relative to the inner membrane mitochondria.
16. Here, what role the f 0 protein plays in the mechanism of oxidizing phosphaeling the respiratory enzymes by Mitchell. Answer: ProteinF. 0 Provides receipt of prostons on an electrochemical gradient to the active centeraTP synthetase enzyme.
17.Relect 2 examples of compounds that inhibit the work of the IV complex of primary depletions. Answer: Cyanide, carbon monoxide.
18. For 2 possible causes of the development of hypoxic hypoenergetic states. Answer: 2 of any variant of 4 possible: a) oxygen deficiency in the external environment; b) disorder of the respiratory organs; c) circulatory disorder; D) Violation of the ability of hemoglobin blood tolerate oxygen.
Option 5.
1. Bring the equation describing the II law of thermodynamics in the form, accepting the thermodynamics of residential objects. Answer : D.S.systems + D.S.environments\u003e 0.
2. Indicate, with what condition, the two reactions conjugate in the energy plan can go spontaneously. Answer : Two energetically conjugate reactions can go spontaneously if the total change in free energy will be negative
3. Give 2 examples of macroeergic compounds from the class of nucleoside polyphosphates. Answer: Any 2 of the following: ATP, GTF, CTF, UTF Go their biposphate analogs
4. Call 2 finite nitrogen-containing protein catabolic products in the human body. Answer : Two any of the following: ammonia, urea, creatinine.
5. Indicate which methods of breaking chemical bonds of nutrients are used in the first phase of catabolism. Answer : Hydrolysis, phosphoroliz.
6. Call 4 final metabolic products formed in the second phase of catabolism. Answer : 4 compounds of reference: water, carbon dioxide, ammonia, urea, creatinine, uric acid.
7. Explain why the metabolic pathways of the third phase of catabolism received the name of common catabolism paths. Answer: These metabolic pathways are the same for the decomposition of any nutrients.
8. Write one of the variants of the overall diagram of dioxigenase reactions encountered in cells. Answer : One of the options: a) R-CH \u003d CH-R 2 +ABOUT 2 -\u003e R1-C (O) H + R-C (O) H (aldehydes) b.) SH2 + O2 -\u003e HO-S-ON. -\u003e S \u003d 0 + H2ABOUT
9. Write using the structural formulas of metabolites, the curtain synthesis reaction in the Krex cycle with the indication of all the connections involved in the reaction. Answer :
10. Name 4 regulatory enzymes participating in the catalysis of partial reactions of the Krebs cycle. Answer : Citrantsintase, IsocitrateTehydrogenase, 2-oxoglutahedheldhydrogenase complex, succinate dehydrogenase.
11. For 2 possible ways to replenish the pool of intermediate metabolites Crex cycle. Answer : a) flow of them from the second phase of catabolism, b) the reaction of the carboxylation of the pyruvate.
12. Here, in which cell compartments are localized by the metabolone cycle of tricarboxylic acids. Answer : In the matrix mitochondria.
13. The name of the IV of the enzyme complex from the main respiratory chain of mitochondria. Answer : Cytochrome S.- oxidase complex
14. Act the total equation describing the operation of the main chain of respiratory enzymes. Answer: Nadn + N "+ 1 / 2o 2 -\u003e Over + +H 2 O.
15. Explain why electrons and protons from a number of oxidized substrates, such as glutamate, isocitrate, malate, etc. are transferred to above +. Answer : The values \u200b\u200bof the redox potentials of these compounds are less than that of NAPH + H +, therefore electrons with these compounds can be transmitted to over + over a gradient of the redox potential.
16. Do you receive a diagram of oxidative phosphorylation reactions at the substrate level of the tricarboxylic acid cycle. Answer
17. The example of a compound that inhibits the work of the III of the main chain of the respiratory enzymes. Answer : Antimycin.
18. Here, in which cell structures are localized mainly by microsomal oxidation processes. Answer : In the membranes of the endoplasmic network.
19. For 3 possible sources of formation of superoxide anion radical in cells. Answer: a) when oxidizingb. atMethb.. 6) apply melectronic oxidationKoqh. 2 having an electron on an oxygen molecule B) with one-electron oxidation of recovered flavines. (Other options are possible).
20. Assist the reaction of the peroxide neutralization catalyzed by glutathioneer peroxidase. Answer: H 2 O 2 + 2 GL-S.N -\u003e Gl-S.- S.-Hl + 2 H 2 o
Option 6.
1. Write an equation by which you can calculate the change in the level of free energy in the course of a different chemical reaction under standard conditions.
Answer : ∆ G. =- 2.303xrXTXl.gK.equilibrium
2. Give the total energy pairing scheme of two parallel in living objects of chemical reactions. Answer :
3. Indicate what the biological role of macroeergic compounds is. Answer : Battery of free energy released during exehergonic reactions, and ensuring the energy of endorgonic reactions.
4. Indicate which part of the energy of nutrients is released in the third phase
catabolism. Answer : 2/3 .
5. Name 5 compounds entering the Krebs Truccarbonic acid cycle from the second phase of catabolism. Answer : Acetyl-CoA, oxaloacetate, 2-oxoglutaterat, fumarate, succinyl-koa.
6. Specify 3 methods of oxidation of compounds used in cells. Answer : Dehydrification, oxygenation, exchanging electrons.
7. Specify 4 functions of biological oxidation in the body. Answer : a) Energy function. b) Plastic function, c) detoxification, d) generation of recovery potentials.
8. List 3 functions of Krebs tricarboxylic cycles. Answer : Energy, plastic, integration.
9. Name the enzymes of the Krebs cycle, the activity of which is oppressed by altogether with high concentrations. Answer : Citrateintase, isocitrate dehydrogenase.
10. Call 3 intermediate products of the Krex cycle used as the source substrates for biosynthesis. Answer : Oxaloacetate, 2-oxoglutate, Succinyl-CoA
11. The name of the III of the enzyme complex from the main respiratory chain of mitochondria. Answer :KoQ.H 2, cytochroms-oxidoreductadasome complex
12. Possess why electrons and protons during the oxidation of a number of substrates, such as succinate, 3-phosphoglycerol, etc., are transferred not to above +, but through flavoproteins on KOQ. Answer : The values \u200b\u200bof the redox potentials of these compounds are higher than that of NAPN +H. + but less than whatKoqtherefore, electrons from these compounds can be transmitted to the redox potential gradient only onKoq.
13. Let the definition of the term "oxidative phosphorylation in the respiratory enzyme circuit". Answer : Synthesis of ATP due to the energy released when moving electrons by respiratory enzyme circuit.
14. Here, what role the f 0 protein plays in the mechanism of oxidizing phosphorylation by the respiratory enzymes by Mitchell. Answer : ProteinF. 0 Provides receipt of prostons on an electrochemical gradient in Active CenteraTP-synthetase enzyme.
15. Give the classification of hypoenergetic states, which is based on the cause of their occurrence. Answer : a) alimentary. 6) .gipoxic. c) Gistotoxic. d). Combined.
16. Do you drive the circuit of the electron carriers with the participation of cytochrome P 450, functioning in the membrane bendoplasmatic network. Answer :
17. The reaction equation catalyzed by the enzyme superoxidedismutase.
Answer : O 2- + 0 2- + 2N + -\u003e H 2 O 2 + O 2
Option 7.
1. Explain why live objects cannot use thermal energy to perform. Answer : ATbiological systems No temperature gradient.
2. Indicate, according to which principle, chemical bonds in certain compounds relate to the ties of the macroergic. Answer: The free energy of the rupture of such a connection should exceed 5 kcal / mol (equivalent:\u003e 21 kj / m).
3. Name 4 classes of macroergic compounds. Answer: Any 4 options from the following: nucleoside polyphosphates, carbonyl phosphates, thioethers. Guanidine phosphates, amino calacelates, aminoacil-TRNA.
4. Specify the amount of the daily need of a person in lipids, expressed in g / kg of body weight. Answer : 1.5 g / kg.
5. Specify the value of the caloric coefficient for carbohydrates. Answer : 4.1 kcal / g.
6. Indicate which part of the common human energy consumption is covered by splitting lipids. Answer : 30%.
7. Indicate what the biological role of the first phase of catabolism. Answer : A sharp decrease in the number of individual compounds entering the second phase.
8. Name 2 metabolic pathways belonging to the third phase of catabolism. Answer : Cycle Truccarboxylic acids, main chain of respiratory enzymes.
9. Write a general diagram of anaerobic dehydrogenation reactions. Answer: Sh 2 + X. -> S.oxidized + HN 2
10. Let the definition of a metabolic path, known as the Krebx tricarboxylic acid cycle. Answer : The cyclic path of mutual transformations of di- and tricarboxylic acids, during which acetyl residue is oxidized to two CO2 molecules.
11.Sill with the help of structural formulas transition of citrate to isocitrate with all participants in the process. Answer :
12. Specify the enzymes of the Krex cycle, the activity of which is altogetherically depressing high concentrations + H +. Answer : Citrantsintase, IsocitrateTehydrogenase, 2-oxoglutaratedehydrogenation complex.
13. Install the reaction of the synthesis of oxaline-acetic acid from the pyruvate with the indication of all participants in the project. Answer :Ch 2 -CO-COOH+ Co. 2 + ATP -\u003e Soon-CH 2 -Co-coxy + ADP + F.
14. Do the general scheme of the main respiratory chain of mitochondria. Answer :
15. The names of the 1 enzyme complex from the main respiratory chain of mitochondria. Answer : Nadn + H +,Koq - oxidoreductase complex.
16. Here, the reason (driving force), forcing the movement of electrons along the carrier system of the main respiratory chain. Answer : The difference between the redox potentials between the compounds at the beginning and at the end of the respiratory chain.
17. Let the definition of the term "oxidative phosphorylation at the substrate level". Answer : Synthesis of ATP using energy highlighted when oxidizing one or another connection.
18. Bring 2 examples of compounds inhibiting the operation of 1 complex of the main chain of respiratory enzymes. Answer : Rothenon, amital sodium.
19. Indicate 2 possible causes of the development of histotoxic hypoenergetic states. Answer : a) blocking the operation of the chain of the respiratory enzymes, b) disagreement of oxidation and phosphorylation.
20. Name 2 compounds whose catabolism involves a microsomal oxidation system. Answer : Tryptophan, phenylalanine.
Introduction to metabolism (biochemistry)
The metabolism or metabolism is a combination of chemical reactions in the body, which provide its substances and the energy necessary for life. The process of metabolism, accompanied by the formation of simpler compounds from complex, is denoted by the term - catabolism. The process coming in the opposite direction and leading, ultimately, to the formation of a complex product from relatively simpler - anabolism. Anabolic processes are accompanied by energy consumption, catabolic - release.
Anabolism and catabolism are not a simple reaction of reactions. Anabolic pathways should differ from the catabolism paths at least one of the enzymatic reactions to be regulated independently, and due to controlling the activity of these enzymes, the total decay rate and synthesis of substances is regulated. Enzymes that determine the speed of the entire process as a whole are called key.
Moreover, the path in which the catabolism of one or another molecule may be unsuitable for its synthesis for energy considerations. For example, the glucose cleavage of glucose to pyruvate is a process consisting of 11 consecutive stages catalyzed by specific enzymes. It would seem that the synthesis of glucose from the Piruvat should be a simple appeal of all these enzymatic stages of its decay. Such a path appears at first glance and the most natural, and most economical. However, in reality, glucose biosynthesis (glukegenesis) in the liver flows differently. It includes only 8 of the 11 enzymatic stages involved in its decay, and 3 missing stages are replaced in it by a completely different set of enzymatic reactions inherent in this biosythynthetic path. In addition, the responses of catabolism and anabolism are often separated by membranes and proceed in different cell compartments.
Table 8.1. Complementation of some metabolic paths in hepatocyte
|
Complement |
Metabolic paths |
|---|---|
|
Cytosol |
Glycoliz, many gluconeogenesis reactions, amino acid activation, fatty acid synthesis |
|
Plasma membrane |
Energy-dependent transport systems |
|
DNA replication, synthesis of various types of RNA |
|
|
Ribosomes |
Synthesis protein |
|
Lysosomes |
Insulation of hydrolytic enzymes |
|
Golgi complex |
Formation of plasma membrane and secretory bubbles |
|
Micromomes |
Localization of catalase and amino acid oxidases |
|
Endoplasmic reticulum |
Synthesis lipid |
|
Mitochondria |
Tricarboxylic acid cycle, fabric breathing chain, oxidation of fatty acids, oxidative phosphorylation |
Metabolism performs 4 functions:
1. Supply the organism of the chemical energy obtained by splitting the rich energy of food substances;
2. The transformation of food substances into the building blocks, which are used in the cell for the biosynthesis of macromolecules;
3. Assembling macromolecular (biopolymers) and supramolecular structures of a living organism, plastic and energy maintenance of its structure;
4. Synthesis and destruction of those biomolecules that are necessary for performing specific features of the cell and the body.
The metabolic path is a sequence of chemical transformations of a particular substance in the body. Intermediate products formed during the transformation process are called metabolites, and the last connection of the metabolic path is the final product. An example of a metabolic path is glycoliz, cholesterol synthesis.
The metabolic cycle is such a metabolic path, one of the finite products of which is identical to one of the connections involved in this process. The most important metabolic cycles in the human body are the cycle of tricarboxylic acids (Krebs cycle) and the ornithine urea cycle.
Almost all metabolic reactions are ultimately related, since the product of one enzymatic reaction serves as a substrate for another, which in this process plays the role of the next stage. Thus, metabolism can be represented as an extremely complex network of enzymatic reactions. If the flow of nutrients in some one part of this network decreases or breaks, then changes may occur in another part of the network in response, in order for this first change to be somehow balanced or compensated. Moreover, both catabolic and anabolic reactions are adjusted in such a way that they proceed most economically, that is, with the lowest energy and substances. For example, the oxidation of nutrients in the cell is performed at a speed, just sufficient to satisfy its energy needs at the moment.
Specific and shared catabolism
Three stages differ in catabolism:
1. The polymers turn into monomers (proteins in amino acids, carbohydrates in monosaccharides, lipids in glycerol and fatty acids). Chemical energy is dissipated in the form of heat.
2. Monomers turn into common products, in the overwhelming majority in acetyl-cola. The chemical energy is partially dissipated in the form of heat, partially accumulates in the form of restored coefficient forms (NADB, FADN2), partially sources in the macroergic bonds of ATP (substrate phosphorylation).
The 1st and 2nd stage of catabolism belong to the specific paths that are unique to the metabolism of proteins, lipids and carbohydrates.
3. The final stage of catabolism is reduced to the oxidation of acetyl-coolas to CO 2 and H 2 O in the reactions of the tricarboxylic acid cycle (Crec cycle) - the general path of catabolism. The oxidative responses of the common catabolism is conjugate with a chain of fabric breathing. At the same time, the energy (40-45%) is in the form of ATP (oxidative phosphorylation).
As a result of the specific and common paths of catabolism, biopolymers (proteins, carbohydrates, lipids) disintegrate to CO 2, H 2 O and NH 3, which are the main finite catabolic products.
Metabolites Normally and with pathology
In a living cage, hundreds of metabolites are formed every second. However, their concentrations are supported at a certain level, which is a specific biochemical constant or reference value. During diseases, there is a change in the concentration of metabolites, which is the basis of biochemical laboratory diagnostics. Normal metabolites include glucose, urea, cholesterol, common serum protein and a number of others. The output of the concentration of these substances beyond the limits of physiological norms (an increase or decline) indicates a violation of their exchange in the body. Moreover, a number of substances in the body of a healthy person are found only in certain biological fluids, which is caused by the specifics of their metabolism. For example, serum proteins normally do not pass through the renal filter and, accordingly, not detected in the urine. But with the inflammation of the kidneys (glomerulonephritis), proteins (primarily albumin) penetrate the glull capsule, appear in the urine - proteinuria and are interpreted as pathological components of urine.
Pathological metabolites are myeloma proteins (Bens-Jones proteins), paraproteins in macrooglobulinemia of valden sticks, accumulation of anomalous glycogen during glycogenases, various fractions of complex lipids during sphingolipidos, etc. They are found only for diseases and for a healthy body is not characteristic.
Levels studying metabolism
Levels of learning metabolism:
1. Whole organism.
2. Isolated organs (perfusable).
3. Tissue sections.
4. Cell cultures.
5. Tissue homogenates.
6. Isolated cell organelles.
7. Molecular level (purified enzymes, receptors, etc.).
Quite often, radioactive isotopes (3 H, 32 p, 14 C, 35 S, 18 O) are used to study metabolism, which are labeled substances introduced into the body. Then you can trace the cell localization of these substances, to determine the half-life and their metabolic paths.
Fig. 8.1. Specific and common catabolic paths
Chapter 9. Biological membranes
The cell represents the biological system, the basis of which is the membrane structures separating the cell from the external environment, forming its compartments (compartments), as well as ensuring the receipt and removal of metabolites, perception and transmission of signals and are structural organizers of metabolic paths.
The agreed functioning of membrane systems - receptors, enzymes, transport mechanisms helps to maintain cell homeostasis and at the same time quickly respond to changes in the external environment.
Membranes are non-meanty supramolecular structures. Proteins and lipids in them are held together by many non-covalent interactions (cooperative by nature).
The main functions of membranes can be attributed:
1. separation of cells from the environment and the formation of intracellular compartments (compartments);
2. Control and regulation of transport of a huge variety of substances through membranes (electoral permeability);
3. Participation in providing intercellular interactions;
4. Perception and signal transmission inside the cell (reception);
5. Localization of enzymes;
6. Energy transforming function.
The membranes are asymmetrical in the structural and functional relationship (carbohydrates are always localized outside and they are not on the inside of the membrane). These are dynamic structures: the protein and lipids included in their composition can move in the membrane plane (lateral diffusion). However, there is also a transition of proteins and lipids on one side of the membrane to another (transverse diffusion, flip flops), which occurs extremely slow. Mobility and fluidity of membranes depend on its composition: the ratios of saturated and unsaturated fatty acids, as well as cholesterol. The membrane fluidity is lower than the greater the saturation of fatty acids in phospholipids and the greater the cholesterol content. In addition, the membrane is characterized by self-assembly.
General properties of cell membranes:
1. Easily permeable for water and neutral lipophilic compounds;
2. To a lesser extent permeable for polar substances (sugar, amides);
3. Poor permeable for small ions (Na +, Cl - et al.);
4. Characterized high electrical resistance;
5. Asymmetry;
6. Can spontaneously restore integrity;
7. Liquidity.
Chemical composition of membranes.
Membranes consist of lipid and protein molecules, the relative amount of which different membranes are widely fluctuated. Carbohydrates are contained in the form of glycoproteins, glycolipids and are 0.5% -10% of the substances of the membrane. According to the liquid-mosaic model of the structure of the membrane (Senjer and Nicholson, 1972) the basis of the membrane is a double lipid layer, in the formation of phospholipids and glycolipids. The lipid bilayer is formed by two rows of lipids, the hydrophobic radicals of which are hidden inside, and the hydrophilic groups are turned out and in contact with the aqueous medium. Protein molecules as if dissolved in lipid bisal and relatively freely "swim in the lipid sea in the form of icebergs on which the trees of glycicalis grow."
Lipids membranes.
Membrane lipids are amphiphilic molecules, i.e. The molecule has both hydrophilic groups (polar heads) and aliphatic radicals (hydrophobic tails), spontaneously forming bilayers, in which lipid tails are addressed to each other. The thickness of one lipid layer is 2.5 nm, of which 1 nm account for the head and 1.5 nm onto the tail. There are three main types of lipids in membranes: phospholipids, glycolipids and cholesterol. The average molar ratio of cholesterol / phospholipids is 0.3-0.4, but in the plasma membrane, this ratio is much higher (0.8-0.9). The presence of cholesterol in the membranes reduces the mobility of fatty acids, reduces the lateral diffusion of lipids and proteins.
Phospholipids can be divided into glyceluphospholipids and sphingophospolipids. The most common glycelofospholipids membranes - phosphatidylcholines and phosphatidylthatonalolamines. Each glycelupholipid, for example phosphatidylcholine, is represented by several dozens of phosphatidylcholines, differing from each other by the structure of fatty acid residues.
The share of glyceluphospholipids accounts for 2-8% of all membrane phospholipids. The most common is phosphatidylositis.
Specific phospholipids of the inner membrane Mitochondria - cardiolipins (diphosphatidglycere), built on the basis of glycerol and two phosphatidic acid residues, are about 22% of all mitochondrial membranes phospholipids.
In the myelin shell of nerve cells in significant quantities contain spingomyelins.
Membranes glycolipids are represented by cerebroids and gangliosides, in which the hydrophobic part is represented by ceramide. The hydrophilic group is a carbohydrate residue - a glycoside bond attached to the hydroxyl group of the first carbon atom of the ceramide. In significant amounts of glycolipids are in the furnaces of brain cells, epithelium and red blood cells. Ganglosides of erythrocytes of different individuals differ in the structure of oligosaccharide chains and exhibit antigenic properties.
Cholesterol is present in all the membranes of animal cells. Its molecule consists of a rigid hydrophobic kernel and a flexible hydrocarbon chain, a single hydroxyl group is a polar head.
Functions of membrane lipids.
Phospho and glycolipids Membranes, in addition to participating in the formation of lipid bilayer, perform a number of other functions. Membranes lipids form a medium for the functioning of membrane proteins that take native conformation in it.
Some membrane lipids are predecessors of secondary intermediaries when transferring hormonal signals. So phosphatidylindold phosphate under the influence of phospholipase with hydrolyzed to diacylglycerol and inositatriphosphate, which are secondary hormone intermediaries.
A number of lipids are involved in fixing bodied proteins. An example of an overlapped protein is acetylcholinesterase, which is fixed on a postsynaptic membrane to phosphatitylinositol.
Membrane proteins.
Membrane proteins are responsible for the functional activity of membranes and their share ranges from 30 to 70%. MEMBRAN proteins differ in their position in the membrane. They can deeply penetrate the lipid bilayer or even piercing it - integral proteins, in different ways to attach to the membrane - surface proteins, or, to covalently contact with it - borrowed proteins. Surface proteins are almost always glycosylated. Oligosaccharide remnants protect protein protein, participate in recognition of ligands and adhesion.
Proteins localized in the membrane perform structural and specific functions:
1. Transport;
2. enzymatic;
3. Receptor;
4. Antigenic.
Mechanisms of Membrane Transport Substances
There are several ways to transfer substances through the membrane:
1. Simple diffusion - This is the transfer of small neutral molecules to the concentration gradient without energy costs and carriers. The easiest is the simple diffusion through the lipid membrane of small non-polar molecules, such as 2, steroids, thyroid hormones. Small polar uncharged molecules - CO 2, NH 3, H 2 O, ethanol and urea - also diffuse with sufficient speed. The diffusion of glycerol is much slower, and glucose is practically unable to go through the membrane. For all charged molecules, regardless of size, the lipid membrane is not permeable.
2. Lightweight diffusion - Transfer of a substance to a concentration gradient without energy costs, but with a carrier. Characteristic for water-soluble substances. Light diffusion differs from a simple larger movement rate and saturation ability. Distinguish two varieties of lightweight diffusion:
Transport on special channels formed in transmemorgic proteins (for example, cationialective channels);
Using protein-translocases that interact with a specific ligand, provide its diffusion by a concentration gradient (ping-pong) (glucose transfer to red blood cells using a glut-1 protein).
The kinetic transfer of substances of lightweight diffusion resembles an enzymatic reaction. For translocase, there is a saturable concentration of ligand, in which all protein binding centers with ligand are occupied, and proteins are operated at maximum speed. Therefore, the vehicle speed of the facilitated diffusion depends not only on the gradient of the concentrations of the portable substance, but also on the number of beack carriers in the membrane.
Simple and lightweight diffusion refers to passive transport, as it happens without energy costs.
3. Active transport - Transport of substance against the concentration gradient (uncharged particles) or an electrochemical gradient (for charged particles), requiring energy costs, most often ATP. Two types of it are distinguished: the primary active transport uses the energy of ATP or the redox potential and is carried out using transport ATP-AZ. The most common in the plasma membrane of human cells Na +, K + - ATP-AZA, CA 2+-AZA, N + -TF-Aza.
With secondaryly active transport, the ion gradient, created on the membrane due to the operation of the system of primary active transport (absorption of glucose cells of the intestinal cells and reabsorption from the primary urine of glucose and amino acids by kidney cells carried out when the Na + ions move along the concentration gradient).
Transfer through the macromolecule membrane. Transport proteins transfer through the cell membrane of polar molecules of small size, but they cannot transport macromolecules, such as proteins, nucleic acids, polysaccharides, or individual particles.
Mechanisms with which cells can absorb such substances or remove them from the cell differ from the mechanisms of transport of ions and polar compounds.
1. Endocytosis. This transfer of a substance from the medium into a cell along with a part of the plasma membrane. By endocytosis (phagocytosis), the cells can absorb large particles, such as viruses, bacteria or cell fragments. The absorption of the liquid and substances dissolved in it using small bubbles is called pinocytosis.
2. Ecocytosis. Macromolecules, such as blood plasma proteins, peptide hormones, digestive enzymes are synthesized in cells and then secreted into the intercellular space or blood. But the membrane is not permeable for such macromolecules or complexes, their secretion occurs by exocytosis. The body has both adjustable and non-regulated exocytosis path. Unregulated secretion is characterized by continuous synthesis of secreted proteins. An example is the synthesis and secretion of collagen fibroblasts for the formation of an intercellular matrix.
For adjustable secretion, storage of molecules prepared for transport bubbles are characteristic. With the help of adjustable secretion, the selection of digestive enzymes occurs, as well as the secretion of hormones and neurotransmitters.
Chapter 10. Energy Exchange. Biological oxidation
Live organisms from the point of view of thermodynamics are open systems. Energy is possible between the system and the environment, which occurs in accordance with the laws of thermodynamics. Each organic compound entering the body has a certain reserve of energy (E). Part of this energy can be used to make useful work. Such energy is called free energy (G). The direction of the chemical reaction is determined by the value of DG. If this value is negative, the reaction proceeds spontaneously. Such reactions are called exercions. If Dg is positive, then the reaction will proceed only when the free energy is received from the outside - these are endergonic reactions. In biological systems, thermodynamically disadvantageous Endergonic reactions can be processed only due to the energy of exercimic reactions. Such reactions are called energy conjugate.
The most important function of many biological membranes is the conversion of one form of energy to another. Membranes with such functions are called energy-forming. Any membrane performing an energy function is capable of converting the chemical energy of oxidized substrates or ATP into electrical energy, namely to the transmembrane difference of electrical potentials (DY) or into the energy of the concentration difference contained in the separated membrane solutions, and vice versa. Among the energy-forming membranes with the most important, the inner membrane of mitochondria, the external cytoplasmic membrane, the membrane of lysosomes and the Golgi complex, sarcoplasma reticulum is possible. The outer membrane mitochondria and the nuclear membrane cannot turn one form of energy to another.
Energy conversion in a living cell is described by the following general scheme:
Energy resources → Δμi → Work
where Δμi is the transmembrane difference of electrochemical potentials of Ion I. Therefore, the processes of energy utilization and the commission due to its work turn out to be conjugate through the formation and use of Δμi. Therefore, this ion can be called the mating ion. The main mating ion in the eukaryot cell is H +, and, respectively, Δμ n + is the main convertible form of energy. The second largest mating ion is Na + (ΔμNa +). While Ca 2+, K + and Cl - are not used to make any work.
Biological oxidation is the process of dehydrogenation of the substrate using the intermediate carriers of hydrogen and its final acceptor. If oxygen appears in the role of the final acceptor, the process is called aerobic oxidation or tissue breathing, if the final acceptor is not represented by oxygen - anaerobic oxidation. Anaerobic oxidation has a limited value in the human body. The main function of biological oxidation is the provision of energy cells in an accessible form.
Fabric breathing is the process of oxidation of hydrogen by oxygen to the water enzymes of a tissue respiratory chain. It flows according to the following scheme:
The substance is oxidized if electrons and protons (hydrogen atoms are at the same time), or an oxygen attaches. The ability of the molecule to give electrons by another molecule is determined by the redox potential (redox potential). Any compound can give electrons only a substance with a higher oxidation and reduction potential. The oxidizer and the reducing agent always form a conjugate pair.
Select 2 types of oxidized substrates:
1. Pyridine-dependent - alcohol or aldehyde - isocitrate, α-ketoglutarate, pyruvate, malate, glutamate, β-hydroxyacyl-coa, β-hydroxybutyrate, - Over-dependent dehydrogenases are involved in their dehydrogenation.
2. Flavin-dependent - are hydrocarbon derivatives - succinate, acyl-coa, glycerol-3-phosphate, choline - during dehydrogenation transmit hydrogen to the FD-dependent dehydrogenase.
The tissue respiration circuit is a sequence of hydrogen proton carriers (H +) and electrons from an oxidized substrate for oxygen localized on the inner membrane mitochondria.
Fig. 10.1. CTD scheme
CTD components:
1. Over-dependent dehydrogenase dehydrated pyridine-dependent substrates and accelerate 2ē and one H +.
2. FAD (FMN) - dependent dehydrogenases accelerate 2 hydrogen atoms (2N + and 2ē). FMN - dependent dehydrogenase dehydrated only NADB, while the phased dehydrogenase oxidize flavine-dependent substrates.
3. The fat-soluble carrier Ubiquinon (coenzyme q, KAQ) - fluently moves through the mitochondrial membrane and accelerates two hydrogen atoms and turns into coqh 2 (restored form - ubiquinol).
4. System of cytochrome - transfers only electrons. Cytochromas iron-containing proteins, a prosthetic group of which is reminded by gem. In contrast to the heme, the iron atom in cytochrome can reversibly move from two to the trivalent state (Fe 3+ + ē → Fe 2+). This ensures the participation of cytochrome in electron transport. Cytochromas act in order of increasing their redox potential and in the respiratory chain are located as follows: B-C 1 -C-A-A 3. Two latter work in association as one Cytochromaoxidase AA 3 enzyme. Cytochromoxidase consists of 6 subunits (2 - cytochrome A and 4 - cytochrome A 3). In cytochrome a 3, in addition to iron there are copper atoms and it transmits electrons directly to oxygen. The oxygen atom is charged negatively and acquires the ability to interact with protons with the formation of metabolic water.
Randle proteins (FES) - contain non-protected iron and participate in redox processes occurring in one-electron mechanism and are associated with flavoproteins and cytochrome b.
Structural organization of the chain of fabric breathing
The components of the respiratory chain in the inner membrane Mihochondria form complexes:
1. I Complex (Nadn-KoKH 2-Heductase) - Takes the electoons from the mitochondrial NADP and transports them to KAQ. Protons are transported into intermambrane space. An intermediate acceptor and carrier of protons and electrons are FMN and iron and iron squirrels. I complex shares the flow of electrons and protons.
2. II Complex - SUCCINAT - COQ - reductase - includes phad-dependent dehydrogenases and iron-terrestrial proteins. It transports electrons and protons from flavine-dependent substrates for ubiquinone, with the formation of intermediate FadN 2.
Ubiquinon easily moves through the membrane and transmits electrons to the III complex.
3. The III complex - KOKH 2 - cytochrome C - reductase - has in its composition cytochrome B and C 1, as well as iron-top proteins. The functioning of the coq with the III complex leads to the separation of the flow of protons and electrons: protons from the matrix are pumped into the intermembrane space of mitochondria, and electrons are transported further along the CTD.
4. IV Complex - cytochrome A - cytochroma oxidase - contains cytochroma oxidase and transports electrons to oxygen from the intermediate carrier of cytochrome C, which is a movable component of the chain.
There are 2 varieties of CTD:
1. Full chain - pyridine-dependent substrates come into it and hydrogen atoms betrayed for over-dependent dehydrogenases.
2. Incomplete (shortened or reduced) CTD in which hydrogen atoms are transmitted from the phased dependent substrates, bypassing the first complex.
ATF oxidative phosphorylation
Oxidative phosphorylation is the process of forming ATP, conjugate with the transport of electrons according to the tissue breathing chain from an oxidized substrate for oxygen. Electrons always strive to move from electronegative systems to electropositive, so their transportation on CTD is accompanied by a decrease in free energy. In the respiratory chain at each stage, the reduction of free energy occurs stepdly. In this case, three areas can be distinguished in which the transfer of electrons is accompanied by a relatively large decrease in free energy. These stages are capable of providing energy to the synthesis of ATP, since the amount of released free energy is approximately equal to the energy required for the synthesis of ATP from ADF and phosphate.
To explain the mechanisms of respiratory conjugation and phosphorylation, a range of hypotheses is put forward.
Mechanochemical or conformational (Green boiler).
In the process of transformation of protons and electrons, the conformation of proteins-enzymes changes. They go to a new, rich in energy conformational state, and then when returning to the original conformation, give energy to the synthesis of ATP.
Hypothesis of chemical pairing (Lipman).
In conjugation of respiration and phosphorylation, "conjugate" substances are involved. They accelerate protons and electrons and interact with H 3 PO 4. At the time of returning protons and electrons, phosphate bond becomes a macroeergic and phosphate group transmitted to ADP to form ATP by substrate phosphorylation. The hypothesis is logical, but still not allocated "conjugate" substances.
Hemioosmotic hypothesis Peter Mitchell (1961)
The main postulates of this theory:
1. The inner membrane mitochondria is impermeable for Ion N + and it -;
2. Due to the electron transport energy through I, III and IV, protons of the respiratory chain complexes are bought from the matrix;
3. An electrochemical potential occurs on the membrane is an intermediate form of energy supply;
4. The return of protons into the matrix of mitochondria through the proton channel ATP synthase is an energy supplier for ATP synthesis according to the scheme
ADF + N 3 RO 4 → ATP + N 2
Evidence of chemioosmotic theory:
1. On the inner membrane there is a Gradient H + and can be measured;
2. Creating a gradient H + in mitochondria is accompanied by a synthesis of ATP;
3. ionophores (separators), destroying the proton gradient, inhibit the synthesis of ATP;
4. Inhibitors that block protons transport along proton channels of ATP synthase, inhibit the synthesis of ATP.
ATP-synthase structure
ATP-synthase - integral protein of the inner membrane mitochondria. It is located in close proximity to the respiratory chain and is indicated as the V complex. ATP-synthase consists of 2 subunits denoted as F 0 and F 1. The hydrophobic complex F 0 is immersed in the inner membrane mitochondria and consists of several protéers forming the channel along which the protons is transferred to the matrix. Subunit F 1 acts into the mitochondrial matrix and consists of 9 protéers. Moreover, three of them bind to subunits F 0 and F 1, forming a kind of leg and are sensitive to oligomycin.
The essence of the chemioosmotic theory: due to the energy of electron transfer by CTD, the protons moves through the inner mitochondrial membrane into the intermambrane space, where the electrochemical potential (Δμ n +) is created, which leads to a conformational protrusion of the active ATP-synthase center, resulting in a possible reverse transport of protons Through the proton channels of ATP-synthase. Upon returning protons, the electrochemical potential is transformed into the energy of the ATP macroergic communication. The resulting ATP with a translocase carrier protein moves to cytosol cells, and in return to the matrix, ADP and FN arr.
The phosphorylation coefficient (P / O) is the number of atoms of inorganic phosphate included in the ATP molecules, in terms of one atom used absorbed oxygen.
Points of phosphorylation - areas in the respiratory chain, where the electoral transport energy is used to generate a proton gradient, and then in the course of phosphorylation, in the form of ATP:
1. 1 point - between pyridine-dependent and flavine-dependent dehydrogenases; 2 item - between cytochromas B and C 1; 3 item - between cytochromas A and A 3.
2. Consequently, when oxidizing over-dependent substrates, the R / O coefficient is 3, since electrons from NADB are transported with the participation of all CTD complexes. The oxidation of the phased dependent substrates comes around the I complex of the respiratory chain and P / O is 2.
Disorders of energy exchange
All living cells constantly need ATP to implement various activities. Violation of any stage of metabolism, leading to the cessation of ATP synthesis, is disastrous for the cell. Fabrics with high energy needs (CNS, myocardium, kidneys, skeletal muscles and liver) are the most vulnerable. The states in which the synthesis of ATP is reduced to combine the term "hypoenergetic". The reasons for these states can be divided into two groups:
Alimentary - fasting and hypovitaminosis B2 and RR - there is a violation of the delivery of oxidized substrates in the CTD or the synthesis of the coenzymes.
Hypoxic - arise in disruption of the delivery or utilization of oxygen in the cell.
Regulation of CTD.
Is carried out using respiratory control.
Respiratory control is the regulation of electron transfer rate by respiratory chain by ATP / ADP. The less this attitude, the more intense the breathing is going and the ATP is actively synthesized. If ATP is not used, and its concentration in the cell increases, the electron flux to oxygen ceases. The accumulation of ADP increases the oxidation of substrates and the absorption of oxygen. The respiratory control mechanism is characterized by high accuracy and is important, since as a result of its operation, the rate of ATP synthesis corresponds to the needs of the cell in energy. ATP reserves in the cell does not exist. The relative concentrations of ATP / ADF in tissues are changed in narrow limits, while energy consumption by the cell may vary in tens of times.
The American biochemist D. Chans proposed to consider 5 states of mitochondria, in which their respiratory speed is limited by certain factors:
1. Disadvantage SH 2 and ADP - breathing speed is very low.
2. Disadvantage SH 2 in the presence of ADP - speed is limited.
3. There is sh 2 and ADF - breathing very actively (limited only by the speed of the transport of ions through the membrane).
4. The lack of ADP if there is SH 2 - breathing is inhibited (respiratory control state).
5. Lack of oxygen, if there is SH 2 and ADP - an anaerobiosis state.
Mitochondria in a resting cell is in a state of 4, at which the speed of breathing is determined by the amount of ADP. During reinforced work, it may be in state 3 (the possibilities of the respiratory chain are exhausted) or 5 (lack of oxygen) - hypoxia.
CTD inhibitors are drugs that block the transfer of electrons by CTD. These include: Barbiturates (amital), which block electrons transporting through i complex of the respiratory chain, antibiotic antimycin blocks the oxidation of cytochrome B; Carbon monoxide and cyanides inhibit cytochromoxidase and block electron transport to oxygen.
Inhibitors of oxidative phosphorylation (oligomycin) are substances that block the transport of H + along the proton channel of ATP-synthase.
Oxidative phosphorylation disabilities (ionophores) are substances that suppress oxidative phosphorylation without affecting the process of transferring electrons by CTD. The mechanism of action of the separators is reduced to the fact that they are fat soluble (lipophilic) substances and have the ability to associate protons and transfer them through the mitochondria internal membrane in the matrix, bypassing the proton channel of ATP-synthase. The energy released is dissipated in the form of heat.
Artificial disabilities - dinitrophenol, vitamin K derivatives (Dicumurol), some antibiotics (valine olinomycin).
Natural disabilities are lipid peroxidation products, long chain fatty acids, large doses of iodine-containing thyroid hormones, thermogenic proteins.
The thermoregulatory function of the tissue respiration is based on disobeds and phosphorylation. Mitochondria of brown adipose tissue produce more heat, as the thermogenin protein present in them dismisses oxidation and phosphoryry. It is important in maintaining the body temperature of newborns.
Regulation of the velocity of reactions of a certain metabolic path is often carried out by changing the speed of one or, possibly two key reactions catalyzed by "regulatory enzymes". Some physicochemical factors controlling the rate of enzymatic reaction, such as the concentration of the substrate (see ch. 9), are of paramount importance when regulating the total rate of product formation of this path of metabolism. At the same time, other factors affecting the activity of enzymes, such as temperature and pH, in warm-blooded animals are constant and practically do not matter to regulate the speed of metabolic processes. (Pay, however, attention to the change in the pH value in the course of the gastrointestinal tract and its effect on digestion; see ch. 53.)
Equilibrium and nonequilibrium reactions
When the equilibrium is reached, the direct and reverse reaction flows at the same rate, and, consequently, the concentration of the product and the substrate remains constant. Many metabolic reactions proceed precisely in such conditions, i.e. are "equilibrium".
In stationary conditions in vivo, the flow of the reaction from left to the right is possible due to the continuous receipt of the substrate and the permanent removal of the product D. This path could function, but there would be few possibilities for regulating its speed by changing the enzyme activity, since an increase in activity would only lend more rapid equilibrium achievement.
In fact, in the metabolic path, as a rule, there are one or more reactions of the "non-equilibrium" type, the concentration of the reactants of which are far from equilibrium. When the reaction is in an equilibrium state, there is a free energy dissipation in the form of heat, and the reaction turns out to be practically irreversible.
By this path, the flow of reactants goes in a certain direction, however, it will be depleted without a control system. The concentrations of enzymes that catalyzing nonequilibrium reactions are usually small, and the activity of enzymes is regulated by special mechanisms; These mechanisms operate on the principle of "one-liming" valve and allow you to control the rate of formation of the product.
Determining the reaction of the metabolic pathway
The reaction determining speed is the first reaction of the metabolic path, the enzyme of which is saturated with a substrate. It can be defined as a "nonequilibrium" reaction characterized by a significantly less than normal substrate concentration. The first glycolysis reaction catalyzed by hexokinase (Fig. 22.2) is an example of such a defining reaction rate.
