Biology of regulatory proteins. Regulatory proteins: origin
Proteins involved in the regulation of metabolism can themselves serve as ligands (for example, peptide hormones), i.e., interact with other proteins, such as hormonal receptors, exerting a regulatory effect. Other regulatory proteins, such as hormone receptors or the regulatory subunit of protein kinase (a cAMP-activated enzyme), have activities controlled by the binding of regulatory ligands (i.e., hormones and cAMP, respectively) (see Chapter 4). In order for the activities of proteins of this class to be specifically regulated by ligands, such molecules must first of all have sites that specifically (and, as a rule, with high affinity) bind the ligand, which gives the molecules the ability to distinguish the ligand from others chemical compounds. In addition, the protein must have such a structure that, as a result of ligand binding, its conformation can change, i.e., provide the possibility of exerting a regulatory effect. For example, in mammals, the specific binding of cAMP to the regulatory subunit of individual protein kinases leads to a decrease in the binding affinity of this subunit to the catalytic subunit of the enzyme (see Chapter 4). This causes the dissociation of both protein subunits of the enzyme. The catalytic subunit, freed from the inhibitory action of the regulatory subunit, is activated and catalyzes the phosphorylation of proteins. Phosphorylation changes the properties of certain proteins, which affects processes under the control of cAMP. The interaction of steroid hormones with their receptors causes conformational changes in the latter that give them the ability to bind to the cell nucleus (see Chapter 4). This interaction also changes other properties of the receptors that are important in mediating the effect of steroid hormones on the transcription of certain types of mRNA.
In order to have such specialized and highly specific functions, proteins, as a result of the evolution of genes that determine their amino acid sequence, had to acquire the structure that they currently have. In some cases, other genes encoding the synthesis of products that modify the regulatory proteins themselves (for example, by glycosylation) also take part in the process. Since gene evolution appears to have occurred through mechanisms such as mutation of preexisting genes and recombination of regions of different genes (as discussed), this placed certain constraints on protein evolution. From an evolutionary perspective, it would probably be easier to modify existing structures than to create entirely new genes. In this regard, the existence of some homology in the amino acid sequences of different proteins may not be unexpected, since their genes could arise due to the evolution of common precursors. Since, as noted above, regions of proteins adapted to bind regulatory ligands, such as cAMP and steroids or their analogues, should already have existed by the time these ligands appeared, it is easy to imagine how modification of the genes of such proteins could lead to the synthesis of other proteins , maintaining high specificity of regulatory ligand binding.
In Fig. Figure 2-2 shows one of the hypothetical schemes for the evolution of primitive glucotransferase into three existing types of regulatory proteins: bacterial cAMP-binding protein (CAP or CRP), which regulates the transcription of several genes encoding enzymes that take part in lactose metabolism, as well as cAMP-binding protein mammals, which regulates the activity of cAMP-dependent protein kinase, which mediates the action of cAMP in humans (see Chapter 4), and adenylate cyclase (see Chapter 4). In relation to bacterial protein and kinase, the ATP-binding regions of primitive glucokinase have evolved to acquire greater cAMP binding specificity. The bacterial protein also acquired additional polynucleotide (DNA)-binding ability. The evolution of the kinase involves the acquisition of glucophosphotransferase ability to phosphorylate proteins. Finally, adenylate cyclase could be formed from glucokinase by replacing the ADP-generating function with a cAMP-generating one. These conclusions cannot but be purely hypothetical; nevertheless, they show how the molecular evolution of the listed regulatory proteins could have occurred.
Rice. 2-2. Proposed origin of cAMP-dependent protein kinase, adenylate cyclase and bacterial cAMP-binding regulatory protein (Baxter, MacLeod).
Although many details are missing from the picture of protein evolution, the current knowledge of the structure of proteins and genes provides some basis for analyzing the question of whether the genes for some polypeptide hormones evolved from a common precursor gene. Individual polypeptide hormones can be grouped according to structural similarity. It is not surprising that hormones belonging to the same group may have similar physiological effects they cause, as well as a similar mechanism of action. Thus, growth hormone (GH), prolactin and chorionic somatomammotropin (placental lactogen) are characterized by a high degree of amino acid sequence homology. Glycoprotein hormones - thyroid-stimulating hormone (TSH), human chorionic gonadotropin (hCG), follicle-stimulating (FSH) and luteinizing (LH) hormones - consist of two subunits, each of which (A-chain) is identical or almost identical in all hormones of a given groups . The amino acid sequence of the B subunits in different hormones, although not identical, has structural homology. It is probably these differences in B-chains that have crucial to impart specificity to the interaction of each hormone with its target tissue. Insulin shows several structural analogues and shares biological activity with other growth factors, such as somatomedin and non-inhibitable insulin-like activity (NIPA).
As for the group of hormones to which growth hormone belongs, the nucleotide sequence of the mRNAs encoding their synthesis has been partially elucidated. Each amino acid requires three nucleotides in the DNA (and therefore in the mRNA transcribed from it). Although this triplet of nucleotides; (codon) corresponds to this particular amino acid; there can be several codons for the same amino acid. Such "degeneracy" genetic code determines the possibility of greater or lesser homology of the nucleotide sequences of these two genes, which determine the structure of the two hormones, than is found in proteins. Thus, if two proteins have random amino acid sequence homology, then the sequences nucleic acids could show large differences. However, with regard to genes encoding the synthesis of hormones of the somatotropin group, this is not the case; The homology of a nucleic acid sequence is higher than that of an amino acid sequence. Human growth hormone and human chorionic somatomammotropin, which have 87% amino acid sequence homology, have 93% nucleic acid sequence homology in their mRNAs. Human and rat growth hormones share 70% amino acid sequence homology, and their mRNAs exhibit 75% nucleic acid sequence homology. In some regions of the mRNA of rat growth hormone and human chorionic somatomammotropin (mRNA of two different hormones in two biological species), the homology is 85% (Fig. 2-3). Thus, only minimal base changes in DNA cause hormone differences. Therefore, these data support the conclusion that the genes for such hormones were formed during evolution from a common predecessor. From the standpoint of the presented ideas about symbols and the reactions they cause, it is significant that each of the three hormones of this group has an effect on growth (see below). Growth hormone is a factor that determines linear growth. Prolactin plays important role in the processes of lactation and thereby ensures the growth of the newborn. Human chorionic somatomammotropin, although its physiological significance has not been precisely established, can have a significant effect on intrauterine growth by directing nutrients entering the mother's body to the growth of the fetus.
Regulatory proteins
(from Lat. regulo - putting in order, putting in order), group . involved in the regulation of various biochem. processes. An important group of regulatory proteins that this article is devoted to are proteins that interact with DNA and control (expression in the characteristics and properties of the organism). The vast majority of these regulatory proteins function at the level transcriptions(synthesis of messenger RNA, or mRNA, on a DNA template) and is responsible for the activation or repression (suppression) of mRNA synthesis (respectively, activator proteins and repressor proteins).
Known approx. 10 repressors. Naib. among them, repressors of prokaryotes (bacteria, blue-green algae), regulating the synthesis of enzymes involved in (lac-repressor) in Escherichia coli (E.coli), and the repressor of bacteriophage A, have been studied. Their action is realized by binding to specific. DNA sections (operators) of the corresponding genes and blocking the initiation of the mRNA encoded by these genes.
A repressor is usually a dimer of two identical polypeptide chains oriented in mutually opposite directions. Repressors physically prevent RNA polymerase join DNA in the promoter region (the binding site of the DNA-dependent RNA polymerase enzyme that catalyzes the synthesis of mRNA on a DNA template) and begin the synthesis of mRNA. It is assumed that the repressor only interferes with initiation and does not affect mRNA elongation.
A repressor can control the synthesis of cells. one protein or a whole series. the expression of which is coordinated. As a rule, these are enzymes that serve one metabolite. path; their genes are part of one (a set of interconnected genes and adjacent regulatory regions).
Mn. repressors can exist in both active and inactive forms, depending on whether or not they are associated with inducers or corepressors (respectively, substrates in the presence of which the rate of synthesis of a particular enzyme is specifically increased or decreased; see Regulators); these interactions have a non-covalent nature.
For efficient gene expression, it is necessary not only for the repressor to be inactivated by the inducer, but also to be realized specifically. positive switch-on signal, which is mediated by regulatory proteins working “in tandem” with the cyclic. adenosine monophosphate (cAMP). The latter binds to specific regulatory proteins (the so-called CAP catabolite gene activator protein, or protein catabolism activator-BAK). This is a dimer with a pier. m. 45 thousand. After binding to cAMP, it acquires the ability to attach to specific. areas on DNA, dramatically increasing the efficiency of the genes of the corresponding operon. In this case, CAP does not affect the rate of growth of the mRNA chain, but controls the stage of transcription initiation - the attachment of RNA polymerase to the promoter. In contrast to the repressor, CAP (in complex with cAMP) facilitates the binding of RNA polymerase to DNA and makes initiation events more frequent. The site where CAP attaches to DNA is adjacent directly to the promoter on the side opposite to where the operator is localized.
Positive regulation (for example, the lac operon of E. coli) can be described by a simplified scheme: with a decrease in the concentration of glucose (the main carbon source), the concentration of cAMP increases, which binds to the CAP, and the resulting complex with the lac promoter. As a result, the binding of RNA polymerase to the promoter is stimulated and the speed of genes that encode enzymes that allow the cell to switch to the use of another carbon source, lactose, increases. There are other special regulatory proteins (for example, protein C), the functioning of which is described by a more complex scheme; they control a narrow range of genes and can act as both repressors and activators.
Repressors and operon-specific activators do not affect the specificity of the RNA polymerase itself. This last level of regulation is implemented in cases involving mass. change in the spectrum of expressed genes. Thus, in E.coli, genes encoding heat shock proteins, which are expressed under a number of stress conditions of the cell, are read by RNA polymerase only when a special regulatory protein, the so-called. factor s 32. A whole family of these regulatory proteins (s-factors), which change the promoter specificity of RNA polymerase, have been found in bacilli and other bacteria.
Dr. a type of regulatory protein changes the catalytic. properties of RNA polymerase (so-called antiterminator proteins). Thus, two such proteins are known in bacteriophage X, which modify the RNA polymerase so that it does not obey cellular termination signals (this is necessary for the active expression of phage genes).
General scheme genetic control, including the functioning of regulatory proteins, also applies to bacteria and eukaryotic cells (all organisms, with the exception of bacteria and blue-green algae).
Eukaryotic. cells respond to external signals (for them these are, for example, hormones) are basically the same as bacterial cells react to changes in nutritional concentration. substances in environment, i.e. by reversible repression or activation (derepression) of individual genes. At the same time, regulatory proteins that simultaneously control the activity large number genes, can be used in various combinations. Similar combination genetic. regulation can provide differentiation. the development of the entire complex multicellular organism thanks to the interaction. relatively small number of key regulatory proteins
The system for regulating gene activity in eukaryotes has additional components. a level not present in bacteria, namely the translation of all nucleosomes (repeating subunits chromatin), included in the transcription unit into an active (decondensed) form in those cells where this gene should be functionally active. It is assumed that a set of specific regulatory proteins that have no analogues in prokaryotes is involved here. These proteins not only recognize specifically. sections of chromatin (or DNA), but also cause certain structural changes in adjacent areas. Regulatory proteins like bacterial activators and repressors appear to be involved in the downstream regulation of individual genes in the activator regions. chromatin.
A broad class of regulatory proteins eukaryotes-receptor proteins steroid hormones.
REGULATORY PROTEINS
(from Latin regulo - put in order, establish), a group of proteins involved in the regulation of various functions. biochem. processes. An important group of protein proteins, which this article is devoted to, are proteins that interact with DNA and control gene expression (gene expression in the characteristics and properties of the organism). The vast majority of such R. b. operates at the level transcriptions(synthesis of messenger RNA, or mRNA, on a DNA template) and is responsible for the activation or repression (suppression) of mRNA synthesis (respectively, activator proteins and repressor proteins).
Known approx. 10 repressors. Naib. among them, repressors of prokaryotes (bacteria, blue-green algae), regulating the synthesis of enzymes involved in lactose metabolism (lac repressor) in Escherichia coli (E. coli), and a repressor of bacteriophage A, were studied. Their action is realized by binding to specific. DNA sections (operators) of the corresponding genes and blocking the initiation of transcription of the mRNA encoded by these genes.
A repressor is usually a dimer of two identical polypeptide chains oriented in mutually opposite directions. Repressors physically prevent RNA polymerase join DNA in the promoter region (the binding site of the DNA-dependent RNA polymerase enzyme that catalyzes the synthesis of mRNA on a DNA template) and begin the synthesis of mRNA. It is assumed that the repressor only interferes with the initiation of transcription and does not affect the elongation of mRNA.
A repressor can control the synthesis of cells. one protein or a number of proteins, the expression of which is coordinated. As a rule, these are serving one metabolism. path; their genes are part of one operon (a set of interconnected genes and adjacent regulatory regions).
Mn. Repressors can exist in both active and inactive forms, depending on whether they are associated or not with inducers or corepressors (respectively, substrates, in the presence of which the rate of synthesis of a particular enzyme specifically increases or decreases; see. Enzyme regulators);
these interactions have a non-covalent nature.
For efficient gene expression, it is necessary not only for the repressor to be inactivated by the inducer, but also to be realized specifically. positive switch-on signal, which is mediated by R. b., working “paired” with a cyclic. adenosine monophosphate (cAMP). The latter binds to specific R. b. (the so-called CAP protein-catabolite gene activator, or protein catabolism activator-BAK). This is a dimer with a pier. m. 45 thousand. After binding to cAMP, it acquires the ability to attach to specific. areas on DNA, sharply increasing the efficiency of transcription of the genes of the corresponding operon. In this case, CAP does not affect the rate of growth of the mRNA chain, but controls the stage of transcription initiation - the attachment of RNA polymerase to the promoter. In contrast to the repressor, CAP (in complex with cAMP) facilitates the binding of RNA polymerase to DNA and makes transcription initiation more frequent. The site where CAP attaches to DNA is adjacent directly to the promoter on the side opposite to where the operator is localized.
Positive regulation (for example, the lac operon of E. coli) can be described by a simplified scheme: with a decrease in the concentration of glucose (the main carbon source), cAMP increases, which binds to the ATS, and the resulting complex with the lac promoter. As a result, the binding of RNA polymerase to the promoter is stimulated and the rate of transcription of genes that encode increases, allowing the cell to switch to the use of another carbon source—lactose. There are other special R. b. (eg, protein C), the functioning of which is described by a more complex scheme; they control a narrow range of genes and can act as both repressors and activators.
Repressors and operon-specific activators do not affect the specificity of the RNA polymerase itself. This last level of regulation is implemented in cases involving mass. change in the spectrum of expressed genes. Thus, in E. coli, genes encoding heat shock, which are expressed under a number of stress conditions of the cell, are read by RNA polymerase only when a special R. b.-t is included in its reference. called factor s 32. A whole family of these R. b. (s-factors) that change the promoter specificity of RNA polymerase have been found in bacilli and other bacteria.
Dr. variety of R. b. changes catalytic properties of RNA polymerase (so-called antiterminator proteins). Thus, two such proteins are known in bacteriophage X, which modify RNA polymerase so that it does not obey cellular signals for transcription termination (this is necessary for the active expression of phage genes).
General scheme of genetic control, including the functioning of R. b., is also applicable to bacteria and eukaryotic cells (all organisms, with the exception of bacteria and blue-green algae).
Eukaryotic. cells respond to external signals (for them this is, for example,) are in principle the same way as bacterial cells react to changes in the concentration of nutrients. in the environment, i.e., through reversible repression or activation (derepression) of individual genes. At the same time, R. b., which simultaneously controls a large number of genes, can be used in various ways. combinations. Similar combination genetic. regulation can provide differentiation. the development of the entire complex multicellular organism thanks to the interaction. relatively small number of key R. b.
The system for regulating gene activity in eukaryotes has additional components. a level not present in bacteria, namely the translation of all nucleosomes (repeating subunits chromatin), included in the transcription unit into an active (decondensed) form in those cells where this one should be functionally active. It is assumed that a set of specific R. b. is involved here, which have no analogues in prokaryotes. These not only recognize specific ones. sections of chromatin (or DNA), but also cause certain structural changes in adjacent areas. R. b., similar to activators and repressors of bacteria, apparently participate in the regulation of subsequent transcription of individual genes in the activating regions. chromatin.
Extensive class of R. b. eukaryotes-receptor proteins steroid hormones.
Amino acid sequence of R. b. encoded so-called regulatory genes. Mutational inactivation of the repressor leads to uncontrolled synthesis of mRNA, and, consequently, of a certain protein (as a result broadcasts protein synthesis on an mRNA matrix). Such organisms are called. constitutive mutants. The resulting loss of the activator leads to a persistent decrease in the synthesis of the regulated protein.
Lit.: Strayer L., Biochemistry, trans. from English, vol. 3, M., 1985, p. 112-25.
P. L. Ivanov.
Chemical encyclopedia. - M.: Soviet Encyclopedia. Ed. I. L. Knunyants. 1988 .
See what “REGULATORY PROTEINS” are in other dictionaries:
squirrels- puff-specific A heterogeneous group of nuclear proteins involved in the process of gene activation in puffs of polytene chromosomes; These proteins include transcription factors themselves (RNA polymerase II, regulatory proteins, etc.), as well as a number... ... Technical Translator's Guide
Pouf-specific proteins- Proteins specific to puffs * puff specific proteins * puff specific proteins are a heterogeneous group of nuclear proteins involved in the process of gene activation in puffs of polytene chromosomes. These proteins include enzymes that... ...
This term has other meanings, see Proteins (meanings). Proteins (proteins, polypeptides) high molecular weight organic matter, consisting of alpha amino acids connected in a chain by a peptide bond. In living organisms... ... Wikipedia
High molecular weight natural polymers built from amino acid residues connected by an amide (peptide) bond. Each B. is characterized specifically. amino acid sequence and individual spaces, structure (conformation). On... ... Chemical encyclopedia
PROTEINS, high-molecular organic compounds, biopolymers, built from 20 types of L a amino acid residues connected in a certain sequence into long chains. Molecular weight proteins vary from 5 thousand to 1 million. Name... ... Encyclopedic Dictionary
Regulatory proteins- * regulatory proteins * regulatory proteins proteins that regulate matrix processes by placing them on regulatory regions of DNA. Proteins that bind to damaged DNA * proteins that bind to DNA * DNA damage binding… … Genetics. Encyclopedic Dictionary
Proteins, high molecular weight organic. compounds built from amino acid residues. They play a primary role in life, performing numerous functions. functions in their structure, development and metabolism. Mol. m. B. from BELKA’ 5000 to many... ...
- (Sciurus), a genus of squirrels. Dl. bodies 20-31 cm. They climb and move well in trees. The long (20-30 cm) bushy tail serves as a rudder when jumping. OK. 40 species, in the North. hemisphere and in the north south. America, in mountain and lowland forests, including island... ... Biological encyclopedic dictionary
PROTEINS, proteins, high molecular weight organic. compounds built from amino acid residues. They play a primary role in the life of all organisms, participating in their structure, development and metabolism. Mol. m. B. from 5000 to mn. million... Biological encyclopedic dictionary
squirrels- proteins, proteins, high-molecular organic substances built from amino acid residues. They play a vital role in the life of all organisms, being part of their cells and tissues and performing catalytic (enzymes), regulatory... ... Agriculture. Large encyclopedic dictionary
G proteins - universal messengers that transmit signals from receptors to cell membrane enzymes.
Currently, more than 50 G proteins are known:
Gs protein activates adenylate cyclase . Weight 80000-90000 Da.
Gi protein inhibits adenylate cyclase . Weight 80000-90000 Da. Through the receptor, it is activated by somatostatin.
Gq protein activates phospholipase C .
G proteins influence activity phosphodiesterase , phospholipase A 2, some types Ca 2+ - and K + -channels .
· G-proteins also provide signal transmission in sensory cells (photoreceptor, olfactory and taste): Light → rhodopsin → Gt → cGMP PDE → (cGMP→GMP)
G proteins are oligomers, consisting of 3 subunits α, β, γ.
The β-subunits (35000 Da) are the same in Gs and Gi proteins.
α-subunits (41000 Da in Gi, 45000 Da in Gs) are encoded by different genes and provide a specific response (“+” or “-”).
STAT proteins.
End of work -
This topic belongs to the section:
Course of lectures on general biochemistry
Govpo ugma federal agency for health and social development.. department of biochemistry..
If you need additional material on this topic, or you did not find what you were looking for, we recommend using the search in our database of works:
What will we do with the received material:
If this material was useful to you, you can save it to your page on social networks:
Tweet |
All topics in this section:
LECTURE No. 1
Topic: Introduction to biochemistry. Enzymes: structure, properties, localization, nomenclature and classification Faculties: therapeutic and prophylactic, medical and preventive, pediatric
Comparison of the catalytic action of enzymes and inorganic catalysts
Similarities between enzymes and inorganic catalysts Difference between enzymes and inorganic catalysts 1. Accelerated only by thermodynamics
The structure of enzymes
Metabolite is a substance that participates in metabolic processes. Substrate is a substance that undergoes a chemical reaction. Pr
Oxidoreductases
Catalyze redox reactions. 2 substances react and 2 are formed, one is oxidized, the other is reduced: Sres + S’oxide ↔ S’res + Soxide Oxide
Transferases
Enzymes of this class take part in the transfer of atomic groups and molecular residues from one compound to another. 2 substances react and 2 are formed: S-G + S’ ↔ S + S’-G.
Isomerases
Interconversions of optical, geometric, positional isomers. 1 substance reacts and 1 is formed. Based on the type of isomerization reaction catalyzed, several subclasses are distinguished:
Ligases (synthetases)
The connection of 2 molecules using the energy of high-energy compounds (ATP, etc.). 3 substances react, 3 substances are formed. Systematic name substrate: sub
Their roles in the regulation of enzyme activity
Faculties: therapeutic and preventive, medical and preventive, pediatric. 2nd course. One of the most important properties living organisms is the ability to be maintained
Allosteric regulation of enzyme catalytic activity
Allosteric enzymes are enzymes whose activity is regulated by the reversible non-covalent attachment of a modulator (activator and inhibitor) to the allosteric center. Al inhibitors
Mechanisms for regulating the number of enzymes
The number of enzymes in a cell depends on the rate of their synthesis and breakdown. Enzyme synthesis is regulated by inducers and repressors. Some substances act as inducers and repressors.
Cell signaling
In multicellular organisms, the maintenance of homeostasis is ensured by 3 systems: 1). nervous, 2). humoral, 3). immune. Regulatory systems function with the participation of signaling molecules
Participation of receptors in transmembrane signal transmission
secondary intermediaries:
Secondary intermediaries (messengers)
Messengers are low-molecular substances that carry hormone signals inside the cell. They have a high rate of movement, cleavage or removal (Ca2+, cAM
Adenylate cyclase (AC)
A glycoprotein with a mass of 120 to 150 kDa, has 8 isoforms, a key enzyme of the adenylate cyclase system, with Mg2+ catalyzes the formation of the secondary messenger cAMP from ATP. AC content
Protein kinase A (PK A)
PC A is present in all cells, catalyzes the reaction of phosphorylation of the OH groups of serine and threonine of regulatory proteins and enzymes, participates in the adenylate cyclase system, and is stimulated by cAMP. PC A consists
Phosphodiesterase (PDE)
PDE converts cAMP and cGMP into AMP and GMP, inactivating the adenylate cyclase and guanylate cyclase system. PDE is activated by Ca2+, 4Ca2+-calmodulin, cGMP. NO synthase
Action NO
NO is a low molecular weight gas, easily penetrates cell membranes and components of the intercellular substance, has a high reactivity, its half-life on average is no more than 5 s, ra
1). 1 Hormone (G) attaches to the Rs receptor to form a hormone-receptor complex, which, through several Gs proteins, activates several adenylate cyclases (hormone-Ri receptor complex through
Sequence of events leading to catalytic activation of enzymes
1). Hormone (G) binds to the R receptor to form a hormone-receptor complex, which activates phospholipase C through the G protein; 2). Phospholipase C breaks down phosphatidylinositol-4,
Sequence of events leading to catalytic activation of enzymes
1). The guanylate cyclase system functions in the lungs, kidneys, intestines, heart, adrenal glands, intestinal endothelium, retina, etc. It is involved in the regulation of water-salt
Cytoplasmic and nuclear receptors
Corticoids act through cytoplasmic and nuclear receptors.
LECTURE No. 3
Topic: Medical enzymology Faculties: therapeutic and preventive, medical and preventive, pediatric. 2nd course. Enzymology - uh
Hereditary enzymopathies
Hereditary enzymopathies are diseases caused by hereditary disorders of the biosynthesis of enzymes or their structure and function. Normal:
Acquired enzymopathies
Acquired enzymopathies are divided into: nutritional, toxic and caused by various pathological conditions of the body. A). Nutritional enzymopathies are diseases
Determination of the activity of organo-, organelle-specific enzymes and their isoenzymes
Determination of the activity of enzymes and their isoenzymes in biological fluids allows us to establish the localization of the pathological process, its stage, severity, as well as the effectiveness of its treatment.
Enzyme therapy
Enzyme therapy is the use of enzymes of animal, bacterial or plant origin and regulators of enzyme activity for therapeutic purposes. Implementation of enzymes
Such as hormone receptors or the regulatory subunit of protein kinase (a cAMP-activated enzyme) have activities that control the binding of regulatory ligands (i.e., hormones and cAMP, respectively). In order for the activities of proteins of this class to be specifically regulated by ligands, such molecules must first of all have sites that specifically (and, as a rule, with high affinity) bind the ligand, which gives the molecules the ability to distinguish ligands from other chemical compounds. In addition, the protein must have such a structure that, as a result of ligand binding, its conformation can change, i.e. provide the ability to provide regulatory action. For example, in mammals, the specific binding of cAMP to the regulatory subunit of individual protein kinases leads to a decrease in the binding affinity of this subunit with the catalytic subunit of the enzyme. This causes the dissociation of both protein subunits of the enzyme. The catalytic subunit, freed from the inhibitory action of the regulatory subunit, is activated and catalyzes the phosphorylation of proteins. Phosphorylation changes the properties of certain proteins, which affects processes under the control of cAMP.
As for the group of hormones to which growth hormone belongs, the nucleotide sequence of the mRNA encoding their synthesis has been partially identified (Baxter J.D. ea, 1979). Each amino acid requires three nucleotides in the DNA (and therefore in the mRNA transcribed from it). Although a given triplet of nucleotides (codon) corresponds to a given amino acid, there can be several codons for the same amino acid. This “degeneracy” of the genetic code determines the possibility of greater or lesser homology of the nucleotide sequences of these two genes, which determine the structure of the two hormones, than is found in proteins. Thus, if two proteins have random amino acid sequence homology, then the nucleic acid sequences could show large differences. However, with regard to genes encoding the synthesis of hormones of the somatotropin group, this is not the case; The homology of the nucleic acid sequence is higher than the homology of the amino acid sequence (Baxter J.D. ea, 1979). Human growth hormone and human chorionic somatomammotropin, which have 87% amino acid sequence homology, have 93% nucleic acid sequence homology in their mRNAs. Human and rat growth hormones share 70% amino acid sequence homology, and their mRNAs exhibit 75% nucleic acid sequence homology. In some regions of the mRNA of rat growth hormone and human chorionic somatomammotropin (mRNA of two different hormones in two biological species), the homology is 85%. Thus, only minimal base changes in DNA cause hormone differences. Therefore, these data support the conclusion that the genes for such hormones were formed during evolution from a common predecessor. From the standpoint of the presented ideas about symbols and the reactions they cause, it is significant that each of the three hormones of this group has an effect on growth. Growth hormone is a factor that determines linear growth. Prolactin plays an important role in lactation processes and thereby ensures the growth of the newborn. Human chorionic somatomammotropin, although its physiological significance is not precisely established, can have a significant effect on intrauterine growth by directing nutrients entering the mother's body that affect fetal growth (