Formation of end products of nitrogen metabolism. End products of nitrogen metabolism

04.10.2020

Tests

1. The largest amount of ammonia is excreted from the body in the nitrogenous component of urine:

Creatinine. Ammonium salts. Indikana. Urea . Uric acid. Urobilinogen.

2. In the exchange of amino acids methionine and serine, as sources of one-carbon radicals in biosynthetic processes, vitamins take an active part as coenzymes:

Vitamin C. Vitamin D. Vitamin B 12. Vitamin K. Thiamin. Folic acid. Vitamin PP. Riboflavin.

3. Ketogenic amino acids include:

Serine. Valine. Leucine. Methionine. Isoleucine ... Histidine. Lysine. Tyrosine.

4. Due to the violation of amino acid metabolism, diseases develop:

Fructosemia. Gout. Alcaptonuria. Myxedema. Albinism Phenylketonuria Rickets.

5. Disorder of amino acid metabolism leads to phenylpyruvic oligophrenia (phenylketonuria):

Tyrosine. Lysine. Phenylalanine. Histidine. Arginine.

6. The reason for the development of alkaptonuria is a violation of amino acid metabolism:

Cysteine. Tryptophan. Tyrosine. Methionine. Histidine. Arginine.

7. The term "glycogenic amino acids" means:

Reduces renal glucose threshold and induces glucosuria. Violate the ability of cells to absorb glucose. They are able to transform into glucose and glycogen. In terms of energy, they can replace glucose. They are able to suppress the process of gluconeogenesis.

8. Ammonia is rendered harmless in the liver by including In the synthesis of urea in the liver, the following substances are directly involved:

Carbon dioxide . Lysine. Ornithine.ATP. Glutamic acid. Aspartate Ammonia Oxaloacetic acid.

9. The following can participate in the neutralization of toxic ammonia:

Acetoacetic acid. Proteins. Monosaccharides. Glutamic acid. Alpha-ketoglutaric acid. Lactic acid.

10. Black color of urine is observed with the disease:

Gout. Phenylketonuria. Alcaptonuria ... Jaundice

11. In case of alkaptonuria, the enzyme is defective:

Phenylalanine monooxygenase. Dioxygenase (oxidase) of homogentisic acid. Fumarylacetoacetic acid hydrolase

12. What enzyme is defective in phenylketonuria?

Phenylalanine monooxygenase... Tyrosinase. Fumariaacetoacetic acid hydrolase

13. In albinism, tyrosine metabolism is impaired:

Oxidation and decarboxylation... Transamination

14. In tyrosinosis, enzymes are defective:

Fumarylacetoacetic acid hydrolase. Tyrosine transaminase

15. The minimum proportion of complete proteins in the child's diet from their total consumption should be:

50%. 75%. 20%

Situational tasks

1. A young mother informed the doctor about the darkening of the diapers during drying. What kind of hereditary disease can you think of? What are the dietary recommendations of the pediatrician?

2. 27. 36 hours after birth, the boy was diagnosed with impaired consciousness and breathing. Natural childbirth, on time. Parents are cousins \u200b\u200band cousins. In the blood serum, the content of ammonia is higher than 1000 μM / l (norm 20-80), the content of urea is 2.5 mmol / l (norm is 2.5-4.5). The content of orotic acid is increased in urine. The child died 72 hours later.

In favor of what congenital metabolic defects do laboratory data indicate?

3. A 5-year-old child after suffering infectious hepatitis has a blood urea content of 1.9 mM / L. What does this analysis show? What are the recommendations of a pediatrician?

4. In the first days after birth, a newborn has vomiting, convulsions, a sharp increase in the content of the amino acid ornithine, and the concentration of urea is very low. What disease does the child have? What recommendations can be used

5. A patient with diabetes mellitus had a high blood urea content. However, during the period of deterioration of the general condition, its concentration in the blood for some reason decreased. Explain the reasons for fluctuations in blood urea levels.

7. A child of 1.5 months has lethargy, lethargy. The examination revealed the content of phenylalanine in the blood of 35 mg / dl (the norm is 1.4-1.9 mg / dl), the content of phenylpyruvate in the urine is 150 mg / day (the norm is 5-8 mg / day). Make a conclusion about the disease, its cause. What dietary recommendations are required in this case?

8. A 22-year-old patient with arginine succinaturia has been successfully treated by prescribing keto analogs of the amino acids phenylalanine, valine, leuin against the background of a low-protein diet. At the same time, the concentration of ammonia in the plasma decreased from 90 to 30 μmol / L, and the excretion of arginine succinate decreased significantly. Explain the mechanism of the therapeutic action of amino acid keto analogs.

9. With a hereditary disease, familial hyperammonemia, there is a persistent increase in the content of ammonia in the blood and the complete absence of citrulline. The main clinical manifestations are associated with damage to the central nervous system. What reaction is blocked in this disease? How will the daily excretion of urea change?

10. A significant amount of homogentisic acid was found in the patient's urine. What hereditary enzymatic defect can be assumed? Write down the reaction blocked in this patient. What are the dietary recommendations for this patient?

What are the disturbances in the digestion of proteins in the gastrointestinal tract? What additional tests are needed?

11. The amount of protein in the diet of children aged 3 and 13 years is recommended by the doctor at the rate of 2.3 g / kg of body weight.

12. A child has been admitted to the children's clinic, who needs to have gastric juice analysis. The introduction of the probe is difficult. How to conduct a study of the secretory function of the stomach?

23. A pediatrician prescribed pepsin to a child with a stomach disorder. What drug is needed additionally? Why?

13. With food, a teenager receives 80 g of protein per day. During this time, 16 g of nitrogen were excreted in the urine. What is the child's nitrogen balance? What does he testify to?

14.It is excreted with the urine of a physically strong high school student

15 g of nitrogen. Should I change the protein content in his diet?

15. The child was admitted to the surgical department with abdominal pain. Laboratory examination revealed a sharp increase in indican in urine. What is the possible cause of this violation?

16. The mother of a child suffering from low acidity of gastric juice, instead of prescribed hydrochloric acid, began to use a solution of citric acid.

Is such a replacement possible? Explain whether this replacement is acceptable or not.

Questions for the final lesson on the topic "Protein and Amino Acid Metabolism"

1. Features of the exchange of proteins and amino acids. Nitrogen balance. Body wear rate. Protein minimum. Criteria for the nutritional value of proteins. Protein diet of young children. Kwashiorkor.

2. Digestion of proteins. Proteinases of the gastrointestinal tract and their enzymes. Substrate specificity of proteinases. Endo- and exopeptidases. Absorption of amino acids. Age characteristics of the processes of digestion and absorption of proteins .

3. Decay of proteins in the large intestine. Decay products and mechanisms of their neutralization in the liver. Features of the course of putrefactive processes in the large intestine of infants .

4. The dynamic state of proteins in the body. Cathepsins. Tissue autolysis and the role of lysosomal damage in this process. Sources and main ways of consuming amino acids. Oxidative deamination of amino acids. Amino acid oxidases, glutamate dehydrogenase. Other types of amino acid deamination.

5. Transamination. Aminotransferases and their coenzymes. The biological significance of transamination reactions. A-ketoglutarate plays a special role in this process. Indirect deamination of amino acids. Clinical significance of determining the activity of transaminases in blood serum.

6. Decarboxylation of amino acids and their derivatives. The most important biogenic amines and their biological role. Breakdown of biogenic amines in tissues.

7. End products of nitrogen metabolism: ammonium salts and urea. The main sources of ammonia in the body. Ammonia neutralization. Urea biosynthesis (ornithine cycle). Connection of the ornithine cycle with the Krebs cycle. The origin of urea nitrogen atoms. Daily excretion of urea. Violations of the synthesis and excretion of urea. Hyperammonemia. Age characteristics of nitrogen excretion of end products from the body of a child under the age of 1 year.

8. Neutralization of ammonia in tissues: reductive amination of α-keto acids, amidation of proteins, synthesis of glutamine. The special role of glutamine in the body. Renal glutaminase. Adaptive change in renal glutaminase activity in acidosis.

9. Features of the exchange of phenylalanine and tyrosine. Use of tyrosine for the synthesis of catecholamines, thyroxine and melanins. Decomposition of tyrosine to fumaric and acetoacetic acids. Hereditary metabolic disorders of phenylalanine and tyrosine: phenylketonuria, alkaptonuria, albinism.

10. Features of the exchange of serine, glycine, cysteine, methionine. The value of tetrahydrofolic acid and vitamin B 12 in the metabolism of one-carbon radicals. Insufficiency of folic acid and vitamin B 12. The mechanism of the bacteriostatic action of sulfa drugs.

11. The relationship of amino acid metabolism with the metabolism of carbohydrates and fats. Glycogenic and ketogenic amino acids. Replaceable and essential amino acids. Biosynthesis of amino acids from carbohydrates.

STRUCTURE AND EXCHANGE OF NUCLEIC ACIDS

1. The composition of RNA includes nitrogenous bases:

Adenine. Guanine. Uracil . Timin. Cytosine.

2. Individual nucleotides in the polynucleotide chain are linked by bonds:

Peptide. Phosphodiester. Disulfide. Hydrogen.

3. Enzymes are involved in the digestion of nucleic acids - constituent parts of food nucleoproteins:

Pepsin. Ribonuclease. Trypsin. Phospholipases. Deoxyribonuclease. Amylase. Nucleotidases. Phosphatase.

4. The smallest molecular weight is possessed by nucleic acids:

DNA. rRNA. tRNA. mRNA.

5. The end product of the breakdown of purine nitrogenous bases in the human body is:

6. The value of daily urinary excretion of uric acid in a healthy adult is:

0.01-0.05 g. 0.06-0.15 g. 0.35-1.5 g. 2.5-5.0 g.

7. The end product of the decomposition of pyrimidine nitrogenous bases in the human body is:

Urea. Uric acid. Ammonium salts. Creatinine.

8. In violation of the exchange of purine nitrogenous bases? Pathological conditions may occur:

Gout. Basedow's disease. Urolithiasis disease. Lesh-Nihan's disease. Hyperammonemia.

9. The building material for the matrix synthesis of nucleic acids is the following substances:

Nucleoside monophosphates. Nucleoside diphosphates. Nucleoside triphosphates. Cyclic nucleotides.

1. The process of RNA biosynthesis is called:

11. Protein biosynthesis, carried out with the participation of polisome and tRNA, is called:

Transcription. Broadcast. Replication. Repair. Recombination.

12. The main way of reproduction of genetic information is called:

Transcription. Broadcast. Replication. Repair. Recombination.

13 The transformation of pro-RNA into "mature" forms is called:

Recombination. Processing. Replication. Broadcast. Termination.

14. Processing and -RNA, i.e. its maturation is reduced:

Removing introns. Removing exons. Specific modification (methylation, deamination, etc.).

15 "Nonsense - codons" (meaningless codons) in the structure of m-RNA are a signal:

Signal to start protein synthesis. Mutantly changed codon. Signal to terminate protein synthesis. Signal for attachment of prosthetic groups to the synthesized protein.

16. The term "degeneracy" of the genetic code means:

The ability of an amino acid to be encoded by more than one codon. The ability of a codon to encode multiple amino acids. The content of the codon is four nucleotides. Content of two nucleotides in the codon.

17. Chargaff's rules, characterizing the features of the bi-helical structure of DNA, include:

A \u003d T. G \u003d C. A \u003d C. G \u003d T. A + G \u003d C + T. A + T \u003d G + C.

17. For the synthesis of pyrimidine bases de novo substances are used:

Carbon dioxide. Glutamate. Glutamine. Aspartate. Alanin.

19. For the formation of the purine cycle during the synthesis of purine nucleotides, substances are used:

Carbon dioxide. Aspartate. Alanin. Glycocol. Glutamine. Derivatives of tetrahydrofolate.

20. The specificity of the interaction of amino acids with t-RNA is due to:

The composition of the anticodon. A feature of the structural organization of tRNA. The specificity of aminoacyl tRNA synthetases. Amino acid structure.

21. For the synthesis of pyrimidine nucleotides are used:

CO 2. G lutamine. Aspartate. Alanin

22. The precursors of the synthesis of purine nucleotides are:

Inosinic acid. Orotic acid. Uric acid

23 Orotataciduria develops when the enzyme is "blocked":

Carbamoyl aspartate transferase. Orotate phosphoribosyltransferase

Xanthine oxidase.

24. The first stage in the synthesis of the pyrimidine ring is:

Carbamoyl phosphate. Ribose-5-phosphate. Orotic acid. Aspartate

25. Nucleotide - a precursor in the synthesis of pyrimidine nucleotides is:

Inosine monophosphate. Orotate monophosphate. Xanthylic acid. Orotic acid

26. The key enzymes in the synthesis of pyrimidine nucleotides are:

27. The key enzymes in the synthesis in the synthesis of purine nucleotides are:

Carbamoylphosphasynthetase. Carbamoyl aspartate transferase. Phosphoribosylamidotransferase

28. With immunodeficiencies, the activity of enzymes is reduced:

Adenosine deaminase. Xanthine oxidase. Purine nucleoside phosphorylase

29. In Lesh-Nihan syndrome, enzyme activity is reduced:

Xanthine oxidase. Adenine phosphoribosyltransferase. Hypoxanthine-guanine phosphoribosyltransferase

30. With orotataciduria, enzyme activity is reduced:

Orotate phosphoribosyltransferase. Dihydroorotate dehydrogenase. Carbamoyl aspartate transferase

31. The process of converting pro-RNA into mature forms is called:

Recombination. Processing. Broadcast. Termination. Replication

32. When splicing occurs:

Cut out copies of introns. Cutting out copies of exons. Connection of informative RNA regions

33. For transcription you need:

DNA. Primer. RNA polymerase. Protein factors. Nucleotide triphosphates. Topoisomerase

34. Enzymes are involved in the synthesis of RNA:

RNA polymerase. DNA polymerase. Topoisomerase. Primazy

35. "Exons" of pro-RNA are called:

Non-coding sites. Accessory proteins. Terminal site. Coding sites. Start site

36. Enzymes are involved in DNA repair:

DNA ligases. DNA polymerase.) DNA restriction enzyme. Primazy

37. Replication requires:

DNA. Primer. I-RNA. Protein factors. Nucleotide triphosphates.

T opoisomerase

38. Enzymes are involved in DNA synthesis:

RNA polymerase. DNA polymerase. Peptidyltransferase. tTopoisomerase. Primazy

39. The following are involved in the regulation of protein synthesis:

Gene regulator. Exon. Gene operator. Repressor. Intron. Structural gene

40. With post-translational protein modification, the following are possible:

Partial proteolysis. Glycosylation. Modification of amino acids. Joining a prosthetic group

41. The process of moving mRNA along the ribosome is called:

Translocation. Broadcast. Termination

42. An enzyme is involved in the formation of a peptide bond in the biosynthesis of proteins:

Peptidyltransferase. Topoisomerase. Helikaza

43.The signal for the beginning and end of the synthesis of the polypeptide chain is:

Certain mRNA codons. Certain enzymes. Certain amino acids

44. The daily excretion of urea in an adult is:

1.0-2.0 g. 20, -30.0 g. 2.0-8.0 g. 35.0-50.0 g. 8.0-20.0 g

0.1-0.3 mM / L. 0.17-0.41 mM / L. 0.05-0.1 mM / L

46. \u200b\u200bThe proportion of uric acid nitrogen in urine in children is:

1-3%. 3-8,5 %. 0,5-1,0 %.

47. The proportion of urea nitrogen in the urine of newborns is:

30% . 75% . 50%.

Situational tasks

1.The patient complains of joint pain. The uric acid content in the blood is 0.26 mmol / l. The amount of sialic acids - 4.5 mmol / l

(norm 2.0-2.6 mmol / l). What disease can be excluded?

2. The child has a genetic defect in the enzyme hypoxanthine-guanine phosphoribosyl transferase. What are the consequences of this?

3. The patient complains of joint pain. The uric acid content in the blood is 0.56 mmol / l. The amount of sialic acids is 2.5 mmol / l (the norm is 2.0-2.6 mmol / l). Which disease is most likely? What diet is indicated?

4. As a result of gene mutation, the sequence of nucleotides in the codon is changed. What can this lead to?

5.A child suffering from hypovitaminosis has a reduced metabolism of nucleic acids. Explain the reasons for the violations. What vitamins are shown in the first place?

6. In diabetes mellitus, the rate of nucleic acid synthesis decreases significantly. Describe the possible causes of this violation.

7. As a result of gene mutation, the sequence of nucleotides in the codon is changed. What can this lead to?

8. Tumor cells are characterized by accelerated cell division and growth. How can this be prevented by influencing the synthesis of nitrogenous bases?

Questions for the final lesson on the topic "Exchange of nucleoproteins"

1. Nucleic acids as polymeric compounds. The composition and structure of nucleotides, their functions in the body. The biological significance of nucleic acids. Levels of structural organization. Species specificity of the primary structure.

2. The main types of nucleic acids in tissues. Their general characteristics. Features of the chemical composition, structure and properties of DNA molecules. Complementarity of nitrogenous bases. Denaturation and DNA renaissance. DNA hybridization "DNA and DNA" RNA.

3. Breakdown of pyrimidine and purine nucleotides in tissues. End products of decay. Features of excretion of uric acid from the body. Hyperuricemia. Gout.

4. Biosynthesis of pyrimidine nucleotides. Allosteric mechanisms of regulation.

5. Biosynthesis of purine nucleotides. The origin of parts of the purine nucleus. The initial stages of biosynthesis. Inosinic acid as a precursor of adenylic and guanylic acids. Allosteric mechanisms of biosynthesis regulation.

6. DNA biosynthesis. Replication and damage repair. DNA biosynthesis enzymes. Matrix. Correspondence of the primary structure of the reaction product to the primary structure of the matrix. Seeding (primer). Matrix role of RNA. Revertase.

7. RNA biosynthesis. RNA polymerase. Transcription as the transfer of information from DNA to RNA. Formation of the primary transcript, its maturation (processing).

8. Protein biosynthesis. Matrix (informational) RNA. The basic postulate of molecular biology: DNA®iRNA®protein. Correspondence of the nucleotide sequence of the gene to the amino acid sequence of the protein (collinearity). The problem of translation (translation) of a four-digit nucleotide record of information into a twenty-digit amino acid record. Characterization of the nucleotide code.

9. Transport RNA (tRNA), structure and function features. Isoacceptor forms of tRNA. Biosynthesis of aminoacyl-tRNA. Significance of high substrate specificity of aminoacyl tRNA synthetases.

10. Biological systems of protein biosynthesis. The structure of ribosomes. The sequence of events in the biosynthesis of the polypeptide chain. Initiation, elongation, termination. Regulation of protein biosynthesis. Inhibitors of matrix biosynthesis: drugs, viral and bacterial toxins. Post-translational change in the polypeptide chain.

The question is complete

Nitrogen exchange

Nitrogen exchange- a set of chemical transformations, reactions of synthesis and decomposition of nitrogenous compounds in the body; an integral part of metabolism and energy. The concept of "nitrogen metabolism" includes protein metabolism (a set of chemical transformations in the body of proteins and products of their metabolism), as well as the exchange of peptides, amino acids, nucleic acids, nucleotides, nitrogenous bases, amino sugars (see. Carbohydrates), nitrogen-containing lipids, vitamins, hormones and other compounds containing nitrogen.

The body of animals and humans receives assimilable nitrogen from food, in which the main source of nitrogenous compounds are proteins of animal and plant origin. The main factor in maintaining nitrogen equilibrium - the state of the nitrogen ovary, in which the amount of nitrogen introduced and excreted is the same - is an adequate intake of protein with food. In the USSR, the daily protein intake in the diet of an adult is taken equal to 100 r, or 16 r protein nitrogen, with an energy consumption of 2500 kcal... Nitrogen balance (the difference between the amount of nitrogen that enters the body with food, and the amount of nitrogen excreted from the body with urine, feces, sweat) is an indicator of the intensity of A. o. in the body. Starvation or insufficient nitrogen nutrition leads to a negative nitrogen balance, or nitrogen deficiency, in which the amount of nitrogen excreted from the body exceeds the amount of nitrogen entering the body with food. A positive nitrogen balance, in which the amount of nitrogen introduced with food exceeds the amount of nitrogen removed from the body, is observed during the growth period of the body, during tissue regeneration processes, etc. State A. o. largely depends on the quality of dietary protein, which, in turn, is determined by its amino acid composition and, above all, by the presence of essential amino acids.

It is generally accepted that in humans and vertebrates A. o. begins with the digestion of nitrogenous food compounds in the gastrointestinal tract. In the stomach, proteins are broken down with the participation of digestive proteolytic enzymes trypsin and gastrixin (see. Proteolysis ) with the formation of polypeptides, oligopeptides and individual amino acids. From the stomach, the food mass enters the duodenum and the lower parts of the small intestine, where the peptides undergo further cleavage, catalyzed by the enzymes of the pancreatic juice trypsin, chymotrypsin and carboxypeptidase, and by the enzymes of the intestinal juice, aminopeptidases and dipeptidases (dipeptidases). Enzymes). Along with peptides. complex proteins (such as nucleoproteins) and nucleic acids are broken down in the small intestine. The intestinal microflora also makes a significant contribution to the breakdown of nitrogen-containing biopolymers. Oligopeptides, amino acids, nucleotides, nucleosides, etc. are absorbed in the small intestine, enter the bloodstream and are carried with it throughout the body. Proteins of body tissues in the process of constant renewal are also subjected to proteolysis under the action of tissue prothases (peptidases and cathepsins), and the breakdown products of tissue proteins enter the blood. Amino acids can be used for new synthesis of proteins and other compounds (purine and pyrimidine bases, nucleotides, porphyrins, etc.), for energy production (for example, through the inclusion of tricarboxylic acids in the cycle), or can be further degraded to form final products A. o., Subject to excretion from the body.

Amino acids supplied as part of food proteins are used to synthesize proteins of organs and tissues of the body. They are also involved in the formation of many other important biological compounds: purine nucleotides (glutamine, glycine, aspartic acid) and pyrimidine nucleotides (glutamine, aspartic acid), serotonin (tryptophan), melanin (phenylalpnine, tyrosine), histamine, adrenalistidine, norepinephrine, tyramine (tyrosine), polyamines (arginine, methionine), choline (methionine), porphyrins (glycine), creatine (glycine, arginine, methionine), coenzymes, sugars and polysaccharides, lipids, etc. The most important chemical reaction for the body, in which almost all amino acids are involved, is transamination, which consists in the reversible enzymatic transfer of the a-amino group of amino acids to the a-carbon atom of keto acids or aldehydes. Transamination is a fundamental reaction of the biosynthesis of nonessential amino acids in the body. The activity of enzymes that catalyze transamination reactions - aminotransferase - is of great clinical and diagnostic value.

Amino acid degradation can proceed in several different ways. Most amino acids are capable of undergoing decarboxylation with the participation of decarboxylase enzymes to form primary amines, which can then be oxidized in reactions catalyzed by monoamine oxidase or diamine oxidase. During the oxidation of biogenic amines (histamine, serotonin, tyramine, g-aminobutyric acid) by oxidases, aldehydes are formed that undergo further transformations, and ammonia, the main pathway of further metabolism of which is the formation of urea.

Another principal way of degradation of amino acids is oxidative deamination with the formation of ammonia and keto acids. Direct deamination of L-amino acids in the body of animals and humans is extremely slow, with the exception of glutamic acid, which is intensively deaminated with the participation of a specific enzyme, glutamate dehydrogenase. Pretransamination of almost all a-amino acids and further deamination of the formed glutamic acid into a-ketoglutaric acid and ammonia is the main mechanism for the deamination of natural amino acids.

The product of various pathways of amino acid degradation is ammonia, which can also be formed as a result of the metabolism of other nitrogen-containing compounds (for example, during the deamination of adenine, which is part of nicotinamide adenine dinucleotide - NAD). The main way of binding and neutralizing toxic ammonia in ureothelic animals (animals in which the end product of A. o is urea) is the so-called urea cycle (synonym: the ornithine cycle, the Krebs-Henseleit cycle), which occurs in the liver. It is a cyclic sequence of enzymatic reactions, as a result of which urea is synthesized from the ammonia molecule or amide nitrogen of glutamine, the amino group of aspartic acid and carbon dioxide. At daily consumption 100 r protein, the daily excretion of urea from the body is about 30 r... In humans and higher animals, there is another way of neutralizing ammonia - the synthesis of dicarboxylic acid amides asparagan and glutamine from the corresponding amino acids. In uricotelic animals (reptiles, birds) the end product of A. o. is uric acid.

As a result of the cleavage of nucleic acids and nucleoproteins in the gastrointestinal tract, nucleotides and nucleosides are formed. Oligo- and mononucleotides with the participation of various enzymes (esterases, nucleotidases, nucleosidases, phosphorylases) are then converted into free purine and pyrimidine bases.

A further way of degradation of the purine bases of adenine and guanine consists in their hydrolytic deamination under the influence of the enzymes adenase and guanase with the formation of hypoxanthine (6-hydroxypurine) and xanthine (2,6-dioxypurine), respectively, which are then converted into uric acid in reactions catalyzed by xanthine oxidase. Uric acid is one of the end products of A. o. and the final product of the exchange of purines in humans is excreted in the urine. Most mammals have the enzyme uricase, which catalyzes the conversion of uric acid to excreted allantoin.

Degradation of pyrimidine bases (uracil, thymine) consists in their reduction with the formation of dihydro derivatives and subsequent hydrolysis, as a result of which b-ureidopropionic acid is formed from uracil, and from it - ammonia, carbon dioxide and b-alanine, and from thymine - b-aminoisobutyric acid acid, carbon dioxide and ammonia. Carbon dioxide and ammonia can be further incorporated into urea through the urea cycle, and b-alanine is involved in the synthesis of the most important biologically active compounds - histidine-containing dipeptides carnosine (b-alanyl-L-histidine) and anserine (b-alanyl-N-methyl-L- histidine), found in the composition of extractive substances of skeletal muscles, as well as in the synthesis of pantothenic acid and coenzyme A.

Thus, various transformations of the most important nitrogenous compounds of the body are linked to each other in a single exchange. Complex process A. o. regulated at the molecular, cellular and tissue levels. Regulation A. about. in the whole organism is aimed at adapting the intensity of A. o. to the changing conditions of the surrounding and internal environment and is carried out by the nervous system both directly and by acting on the endocrine glands.

In healthy adults, the content of nitrogenous compounds in organs, tissues, and biological fluids is at a relatively constant level. Excess nitrogen from food is excreted in urine and feces, and if there is a lack of nitrogen in food, the body's needs for it can be covered through the use of nitrogenous compounds of body tissues. Moreover, the composition urine varies depending on the characteristics of A. about. and the state of nitrogen balance. Normally, with an unchanged diet and relatively stable environmental conditions, a constant amount of end products of A. o. Is released from the body, and the development of pathological conditions leads to its sharp change. Significant changes in the excretion of nitrogenous compounds in the urine, primarily the excretion of urea, can also be observed in the absence of pathology in the case of a significant change in diet (for example, when the amount of protein consumed changes), and the concentration of residual nitrogen (see. Residual nitrogen ) in the blood changes slightly.

When researching A. about. it is necessary to take into account the quantitative and qualitative composition of food intake, the quantitative and qualitative composition of nitrogenous compounds excreted in the urine and feces and contained in the blood. To study A. about. use nitrogenous substances labeled with radionuclides of nitrogen, phosphorus, carbon, sulfur, hydrogen, oxygen, and observe the migration of the label and its inclusion in the composition of the final products of the A. o. Labeled amino acids, for example 15 N-glycine, are widely used, which are introduced into the body with food or directly into the blood. A significant part of the labeled glycine nitrogen from food is excreted in the urine in the composition of urea, while the other part of the label enters tissue proteins and is excreted from the body extremely slowly. Research A. o. it is necessary for the diagnosis of many pathological conditions and monitoring the effectiveness of treatment, as well as in the development of rational dietary regimens, incl. therapeutic (see. Therapeutic food ).

A. pathology about. (up to very significant) causes protein deficiency. It can be caused by general malnutrition, prolonged deficiency of protein or essential amino acids in the diet, lack of carbohydrates and fats, which provide energy for protein biosynthesis in the body. Protein deficiency may be due to the predominance of protein breakdown processes over their synthesis, not only as a result of alimentary deficiency of protein and other essential nutrients, but also during heavy muscle work, trauma, inflammatory and dystrophic processes, ischemia, infection, extensive burns, defect in the trophic function of the nervous system, deficiency of hormones of anabolic action (growth hormone, sex hormones, insulin), excessive synthesis or excessive intake of steroid hormones from outside, etc. Violation of protein assimilation in pathology of the gastrointestinal tract (accelerated evacuation of food from the stomach, hypo- and anacid states, blockage of the excretory duct of the pancreas, weakening of the secretory function and increased motility of the small intestine with enteritis and enterocolitis, impaired absorption in the small intestine, etc. ) can also lead to protein deficiency. Protein deficiency leads to discoordination A. about. and is characterized by a pronounced negative nitrogen balance.

There are known cases of violation of the synthesis of certain proteins (see. Immunopathology, Fermentopathies), as well as genetically determined synthesis of abnormal proteins, for example, when hemoglobinopathies, multiple myeloma (see. Paraproteinemic hemoblastosis ) and etc.

The pathology of A. o., consisting in a violation of the exchange of amino acids, is often associated with anomalies of the transamination process: a decrease in the activity of aminotransferases during hypo- or avitaminosis B 6, a violation of the synthesis of these enzymes, a lack of keto acids for transamination due to inhibition of the diabetes, etc. A decrease in the intensity of transamination leads to inhibition of the deamination of glutamic acid, and this, in turn, to an increase in the proportion of amino acid nitrogen in the residual blood nitrogen (hyperaminoacidemia), general hyperazotemia and aminoaciduria. Hyperaminoacidemia, aminoaciduria, and general azotemia are characteristic of many types of pathology of A. o. With extensive liver damage and other conditions associated with massive breakdown of protein in the body, the processes of deamination of amino acids and the formation of urea are disrupted in such a way that the concentration of residual nitrogen and the content of amino acid nitrogen in it increase against the background of a decrease in the relative content of urea nitrogen in the residual nitrogen (the so-called production azotemia).

Production azotemia, as a rule, is accompanied by the excretion of excess amino acids in the urine, since even in the case of normal functioning of the kidneys, the filtration of amino acids in the renal glomeruli occurs more intensively than their reabsorption in the tubules. Kidney disease, obstruction of the urinary tract, impaired renal circulation lead to the development of retention azotemia, accompanied by an increase in the concentration of residual nitrogen in the blood due to an increase in the blood urea (see. Renal failure ). Extensive wounds, severe burns, infections, damage to the tubular bones, spinal cord and brain, hypothyroidism, Itsenko-Cushing's disease and many other serious diseases are accompanied by aminoaciduria. It is also characteristic of pathological conditions occurring with impaired reabsorption processes in the renal tubules: Wilson-Konovalov disease (see. Hepatocerebral dystrophy ), Fanconi nephronophthisis (see. Rickets-like diseases ), etc. These diseases are among the numerous genetically determined disorders of A. o. Selective disturbance of cystine reabsorption and cystinuria with generalized disturbance of cystine metabolism against the background of general aminoaciduria accompanies the so-called cystinosis. In this disease, cystine crystals are deposited in the cells of the reticuloendothelial system. Hereditary disease phenylketonuria characterized by a violation of the conversion of phenylalanine to tyrosine as a result of a genetically determined deficiency of the enzyme phenylalanine - 4-hydroxylase, which causes the accumulation of unconverted phenylalanine and its metabolic products - phenylpyruvic and phenylacetic acids in the blood and urine. Disruption of the transformations of these compounds is also characteristic of viral hepatitis.

Tyrosinemia, tyrosinuria and tyrosinosis are noted in leukemia, diffuse connective tissue diseases (collagenoses) and other pathological conditions. They develop as a result of a violation of tyrosine transamination. A congenital anomaly in the oxidative transformations of tyrosine underlies alkaptonuria, in which an unconverted metabolite of this amino acid, homogentisic acid, accumulates in the urine. Disorders of pigment metabolism with hypocorticism (see. Adrenal glands ) are associated with inhibition of the conversion of tyrosine to melanin due to inhibition of the enzyme tyrosinase (complete loss of synthesis of this pigment is characteristic of congenital pigmentation anomalies - albinism).

In chronic hepatitis, diabetes mellitus, acute leukemia, chronic myelo- and lymphocytic leukemia, lymphogranulomatosis, rheumatism and scleroderma, the exchange of tryptophan and its metabolites 3-hydroxykynurenine, xanturenic and 3-hydroxyanthranilic acids, which have toxic properties, are disrupted. To A. pathology of the lake. also include conditions associated with impaired renal excretion of creatinine and its accumulation in the blood. An increase in creatinine excretion accompanies a hyperfunction of the thyroid gland, and a decrease in creatinine excretion with an increased excretion of creatine - hypothyroidism.

With massive disintegration of cellular structures (starvation, heavy muscular work, infections, etc.), a pathological increase in the concentration of residual nitrogen is noted due to an increase in the relative content of uric acid nitrogen in it (normally, the concentration of uric acid in the blood does not exceed - 0.4 mmol / l).

In old age, the intensity and volume of protein synthesis decrease due to the direct suppression of the biosynthetic function of the body and the weakening of its ability to assimilate food amino acids; a negative nitrogen balance develops. Disorders of purine metabolism in elderly people lead to the accumulation and deposition of uric acid salts - urates in muscles, joints and cartilage. Correction of violations A. o. in old age, it can be carried out through special diets containing complete animal proteins, vitamins and minerals, with a limited content of purines.

Nitrogen metabolism in children is distinguished by a number of features, in particular, a positive nitrogen balance as a necessary condition for growth. The intensity of processes A. o. during the growth of the child, it undergoes changes, especially pronounced in newborns and young children. During the first 3 days of life, the nitrogen balance is negative, which is explained by insufficient intake of protein from food. During this period, a transient increase in the concentration of residual nitrogen in the blood (the so-called physiological azotemia) is detected, sometimes reaching 70 mmol / l; by the end of the 2nd week.

in life, the concentration of residual nitrogen decreases to the level observed in adults. The amount of nitrogen excreted by the kidneys increases during the first 3 days of life, after which it decreases and again begins to increase from the 2nd week. life in parallel with the increasing amount of food.

The highest assimilation of nitrogen in a child's body is observed in children during the first months of life. Nitrogen balance is noticeably approaching equilibrium in the first 3-6 months. life, although it remains positive. The intensity of protein metabolism in children is quite high - in children of the 1st year of life, about 0.9 r squirrel for 1 kg body weight per day, at 1-3 years - 0.8 g / kg /days, for preschool and school children - 0.7 g / kg /days

The average values \u200b\u200bof the requirement for essential amino acids, according to the FAO WHO (1985), in children is 6 times higher than in adults (an essential amino acid for children under the age of 3 months is cystine, and up to 5 years - and histidine). The processes of amino acid transamination in children are more active than in adults. However, in the first days of life in newborns, due to the relatively low activity of some enzymes, hyperaminoacidemia and physiological aminoaciduria are noted as a result of functional immaturity of the kidneys. In addition, premature infants have an overload type of aminoaciduria. the content of free amino acids in their blood plasma is higher than that of term infants. In the first week of life, the nitrogen of amino acids is 3-4% of the total nitrogen of urine (according to some sources, up to 10%), and only by the end of the 1st year of life, its relative content decreases to 1%. In children of the 1st year of life, the excretion of amino acids per 1 kg body weight reaches the values \u200b\u200bof their excretion in an adult, the excretion of amino acid nitrogen, reaching 10 mg / kg body weight, in the 2nd year of life rarely exceeds 2 mg / kg body weight. In the urine of newborns, the content of taurine, threonine, serine, glycine, alanine, cystine, leucine, tyrosine, phenylalanine, and lysine is increased (compared to that of an adult). In the first months of life, ethanolamine and homocytrulline are also found in the child's urine. The amino acids proline and [hydr] hydroxyproline predominate in the urine of children 1 year of age.

Studies of the most important nitrogenous components of urine in children have shown that the ratio of uric acid, urea and ammonia changes significantly during growth. So, the first 3 months. life is characterized by the lowest content of urea in urea (2-3 times less than in adults) and the highest excretion of uric acid. Children in the first three months of life excrete 28.3 mg / kg body weight of uric acid, and adults - 8.7 mg / kg... The relatively high excretion of uric acid in children during the first months of life sometimes contributes to the development of uric acid infarction of the kidneys. The amount of urea in the urine increases in children aged 3 to 6 months, while the uric acid content decreases at this time. The ammonia content in the urine of children in the first days of life is low, but then it increases sharply and remains at a high level throughout the entire 1 year of life.

A characteristic feature of A. about. in children, physiological creatinuria is present. Creatine is also found in the amniotic fluid; in urine, it is determined in quantities exceeding the content of creatine in the urine of adults, from the period of neonatal to puberty. The daily excretion of creatinine (dehydroxylated creatine) increases with age, at the same time, as the child's body weight increases, the relative content of nitrogen creatinine in urine decreases. The amount of creatinine excreted in the urine per day in full-term newborns is 10-13 mg / kg, in premature babies 3 mg / kg, in adults does not exceed 30 mg / kg.

If a congenital disorder is identified in the family, A. o. it is necessary to conduct

Question short

Isolation of end products of nitrogen metabolism

Uric acid is one of the most important end products of nitrogen metabolism in humans. Normally, its concentration in blood serum in men is 0.27- 0.48 mmol-l-1, in women 0.18-0.38 mmol-l-1; daily urinary excretion ranges from 2.3 to 4.5 mmol (400-750 mg). In humans, uric acid is excreted, and in many mammals there is an enzyme called uricase, which oxidizes uric acid to allantoin. In the body of a healthy person, the formation and excretion of uric acid per day ranges from 500 to 700 mg. Most of uric acid (up to 80%) is formed as a result of the metabolism of endogenous nucleic acids, only about 20% is associated with purines supplied with food. The kidneys excrete about 500 mg of uric acid per day, 200 mg are removed through the gastrointestinal tract.

Functional proteinuria. Functional proteinuria, the exact processes of which have not been determined, include erect, idiopathic inconsistent, excretion of protein in the urine of straining, feverish appearance of protein in the urine, and excretion of protein in the urine of obesity.

Orthostatic proteinuria is characterized by the appearance of a polypeptide in the urina with prolonged inactivity or pacing, with its rapid disappearance when the body posture changes to a perpendicular one. The appearance of protein in the urine in most cases does not exceed one g / day, is glomerular and nonselected, the procedure for its appearance is indistinct. More often it is noted in adolescence, in half of the patients it is cured after a while. The mechanism of formation, perhaps, is combined with an abnormally exacerbated response of the renal circulation to a change in the placement of the trunk.

The definition of orthostatic proteinuria is set by combining the following conditions:

The age of the patients is 13 to twenty years;

Closed type of the appearance of protein in the urine, the absence of other signs of renal impairment (restructuring of the urinary sediment, an increase in the pressure that the blood in the artery exerts on its wall, changes in the vessels of the inner surface of the eyeball);

Only the orthostatic course of the appearance of protein in the urine, when in the studies of urine collected after the subject was in the supine position (including the next morning before getting out of bed), there is no protein.

To prove this diagnosis, a vertical torso check must be performed. To do this, urine is collected in the morning before getting out of bed, then after being in a perpendicular position for some time (movement with a stick behind the back to deploy the spinal column). Diagnostics gives even more accurate results when the morning (night) lobe of urina merges (since residual urine is possible in vesica urinaria), and the initial portion is selected after a short presence of the patient in the supine position.

At a young age, in turn, the primary inconsistent appearance of protein in the urine is possible, which is established in healthy individuals during a medical examination and disappears during subsequent urine tests.

Proteinuria of exertion is detected in twenty percent of healthy individuals (even athletes) after intense physical exertion. The protein is detected in the initial prepared portion of urine. excretion of protein in the urine in a manner associated with tubular pathology. It is assumed that the algorithm for the appearance of protein in urine is combined with recombination of blood flow and relative ischemia of the proximal regions of the nephron.

The febrile appearance of protein in the urine occurs in severe hot conditions, in particular in children and seniors. Feverish excretion of protein in the urine has a predominantly glomerular course. The processes of this type of proteinuria are poorly understood, the possible importance of increasing glomerular filtration along with short-lived damage to the glomerular filter by protective complexes is being studied.

Excretion of protein in the urine with pathological excess body weight. Excretion of protein in the urine is often observed with abnormal fat deposition in the body. (body weight over 115 kilograms). According to J.P. Domfeld (1989), among one thousand patients with pathological fat deposition in the body. 420 was diagnosed with urinary protein excretion without regeneration of urine sediment; also shows precedents of nephrotic syndrome. It is assumed that the underlying cause of the formation of such proteinuria is the distortion of blood circulation in the accumulation of highly fenestrated capillaries (increased pressure in the group of capillaries of the renal corpuscle, increased filtration rate) associated with an increase in pathological excess body weight. the concentration of the polypeptide hormone produced by the kidney due to a decrease in blood pressure and hypertensive, which decreases during fasting. With weight loss, as well as with treatment with ACE inhibitors, the excretion of protein in the urine can be reduced, and also lost.

In addition, proteinuria can be of extrarenal origin. In the presence of leukocytes in the analysis of urine and especially the appearance of blood in the urine, a certifying reaction to the polypeptide may be the result of the disintegration of blood cells during prolonged standing of urine; in this situation, the appearance of protein in the urine in excess of 0.3 grams / day seems abnormal. Sedimentary polypeptide tests are capable of giving false positive results in the presence of iodine-containing contrast materials in urina, a considerable number of similar Penicillinum preparations, as well as a drug from the group of semisynthetic betalactam antibiotics, metabolic products of sulfanilamide preparations.

Similar information.

The body of animals and humans receives assimilable nitrogen from food, in which the main source of nitrogenous compounds are proteins of animal and plant origin. The main factor in maintaining nitrogen equilibrium — the state of nitrogen ovarian cancer, in which the amount of nitrogen input and output is the same — is an adequate intake of protein from food. In the USSR, the daily protein intake in the diet of an adult is taken equal to 100 r, or 16 r protein nitrogen, with an energy consumption of 2500 kcal... Nitrogen balance (the difference between the amount of nitrogen that enters the body with food, and the amount of nitrogen excreted from the body with urine, feces, sweat) is an indicator of the intensity of A. o. in organism. Fasting or insufficient nitrogen nutrition leads to a negative nitrogen balance, or nitrogen deficiency, in which the amount of nitrogen excreted from the body exceeds the amount of nitrogen entering the body with food. A positive nitrogen balance, in which the amount of nitrogen introduced with food exceeds the amount of nitrogen removed from the body, is observed during the growth period of the body, during tissue regeneration processes, etc. A. o. largely depends on the quality of dietary protein, which, in turn, is determined by its amino acid composition and, above all, by the presence of essential amino acids.

It is generally accepted that in humans and vertebrates A. o. begins with the digestion of nitrogenous food compounds in the gastrointestinal tract. In the stomach, proteins are broken down with the participation of digestive proteolytic enzymes trypsin and gastrixin (see. Proteolysis ) with the formation of peptides, oligopeptides and individual amino acids. From the stomach, the food mass enters the duodenum and the lower parts of the small intestine, where the peptides undergo further cleavage, catalyzed by the enzymes of the pancreatic juice trypsin, chymotrypsin and carboxypeptidase, and by the enzymes of the intestinal juice, aminopeptidases and dipeptidases (dipeptidases). Enzymes). Along with peptides. complex proteins (such as nucleoproteins) and nucleic acids are cleaved in the small intestine. The intestinal microflora also makes a significant contribution to the breakdown of nitrogen-containing biopolymers. Oligopeptides, amino acids, nucleotides, nucleosides, etc. are absorbed in the small intestine, enter the bloodstream and are carried with it throughout the body. Proteins of body tissues in the process of constant renewal are also subjected to proteolysis under the action of tissue prothases (peptidases and cathepsins), and the breakdown products of tissue proteins enter the blood. Amino acids can be used for new synthesis of proteins and other compounds (purine and pyrimidine bases, nucleotides, porphyrins, etc.), for energy production (for example, through the inclusion of tricarboxylic acids in the cycle), or can be further degraded to form final products A. o., Subject to excretion from the body.

Amino acid degradation can proceed through several different pathways. Most amino acids are capable of undergoing decarboxylation with the participation of decarboxylase enzymes to form primary amines, which can then be oxidized in reactions catalyzed by monoamine oxidase or diamine oxidase. During the oxidation of biogenic amines (histamine, serotonin, tyramine, g-aminobutyric acid) by oxidases, aldehydes are formed, which undergo further transformations, and ammonia, the main pathway of further metabolism of which is the formation of urea.

Another principal pathway for the degradation of amino acids is oxidative deamination with the formation of ammonia and keto acids. Direct deamination of L-amino acids in the body of animals and humans is extremely slow, with the exception of glutamic acid, which is intensively deaminated with the participation of a specific enzyme, glutamate dehydrogenase. Pretransamination of almost all α-amino acids and further deamination of the resulting glutamic acid into α-ketoglutaric acid and ammonia is the main mechanism for deamination of natural amino acids.

Degradation of pyrimidine bases (uracil, thymine) consists in their reduction with the formation of dihydro derivatives and subsequent hydrolysis, as a result of which b-ureidopropionic acid is formed from uracil, and from it - ammonia, carbon dioxide and b-alanine, and from thymine - b-aminoisobutyric acid acid, carbon dioxide and ammonia. Carbon dioxide and ammonia can be further incorporated into urea through the urea cycle, and b-alanine is involved in the synthesis of the most important biologically active compounds - histidine-containing dipeptides of carnosine (b-alanyl-L-histidine) and anserine (b-alanyl-N-methyl-L- histidine), found in the composition of extractive substances of skeletal muscles, as well as in the synthesis of pantothenic acid and coenzyme A.

A. pathology about. (up to very significant) causes protein. It can be caused by general malnutrition, prolonged deficiency of protein or essential amino acids in the diet, lack of carbohydrates and fats, which provide energy for protein biosynthesis in the body. Protein may be due to the predominance of protein breakdown processes over their synthesis, not only as a result of alimentary deficiency of protein and other essential nutrients, but also during heavy muscular work, trauma, inflammatory and dystrophic processes, ischemia, infection, extensive ah, defect in the trophic function of the nervous system , deficiency of hormones of anabolic action (growth hormone, sex hormones, insulin), excessive synthesis or excessive intake of steroid hormones from the outside, etc. Violation of protein assimilation in pathology of the gastrointestinal tract (accelerated evacuation of food from the stomach, hypo- and anacid states, blockage of the excretory duct of the pancreas, weakening of the secretory function and increased motility of the small intestine with enteritis and enterocolitis, impaired absorption in the small intestine, etc. ) can also lead to protein deficiency. Protein leads to discoordination of A. o. and is characterized by a pronounced negative nitrogen balance.

The pathology of A. o., Consisting in a violation of the exchange of amino acids, is often associated with anomalies of the transamination process: a decrease in the activity of aminotransferases during hypo- or avitaminosis B 6, a violation of the synthesis of these enzymes, a lack of keto acids for transamination in connection with the inhibition of the tricarboxylic acid cycle during hypoxia and sugar e, etc. A decrease in the intensity of transamination leads to inhibition of the deamination of glutamic acid, and this, in turn, to an increase in the proportion of amino acid nitrogen in the residual blood nitrogen (hyperaminoacidemia), general hyperazotemia and aminoaciduria. Hyperaminoacidemia, aminoaciduria, and general azotemia are characteristic of many types of pathology of A. o. With extensive liver damage and other conditions associated with massive breakdown of protein in the body, the processes of deamination of amino acids and the formation of urea are disrupted in such a way that the concentration of residual nitrogen and the content of amino acid nitrogen in it increase against the background of a decrease in the relative content of urea nitrogen in the residual nitrogen (the so-called production azotemia).

Production azotemia, as a rule, is accompanied by the excretion of excess amino acids in the urine, since even in the case of normal functioning of the kidneys, the filtration of amino acids in the renal glomeruli occurs more intensively than their reabsorption in the tubules. Kidney disease, obstruction of the urinary tract, impaired renal circulation lead to the development of retention azotemia, accompanied by an increase in the concentration of residual nitrogen in the blood due to an increase in the blood urea (see. Renal failure ). Extensive wounds, severe and, infections, damage to tubular bones, spinal cord and brain, Itsenko-Cushing's disease and many other serious diseases are accompanied by aminoaciduria. It is also characteristic of pathological conditions occurring with impaired reabsorption processes in the renal tubules: Wilson-Konovalov disease (see. Hepatocerebral dystrophy ), Fanconi nephronophthisis (see. Rickets-like diseases ), etc. These diseases are among the numerous genetically determined disorders of A. o. Selective disturbance of cystine reabsorption and cystinuria with generalized disturbance of cystine metabolism against the background of general aminoaciduria accompanies the so-called cystinosis. In this disease, cystine crystals are deposited in the cells of the reticuloendothelial system. Hereditary disease phenylketonuria characterized by a violation of the conversion of phenylalanine to tyrosine as a result of a genetically determined deficiency of the enzyme phenylalanine - 4-hydroxylase, which causes the accumulation of unconverted phenylalanine and its metabolic products - phenylpyruvic and phenylacetic acids in the blood and urine. Disruption of the transformations of these compounds is also characteristic of viral hepatitis.

Tyrosinemia, tyrosinuria and tyrosinosis are noted with ah, diffuse connective tissue diseases (collagenoses) and other pathological conditions. They develop as a result of a violation of tyrosine transamination. A congenital anomaly in the oxidative transformations of tyrosine underlies alkaptonuria, in which an unconverted metabolite of this amino acid, homogentisic acid, accumulates in the urine. Disorders of pigment metabolism with hypocorticism (see. Adrenal glands ) are associated with inhibition of the transformation of tyrosine into melanin due to inhibition of the enzyme tyrosinase (complete loss of synthesis of this pigment is characteristic of congenital pigmentation anomalies - a).

In life, the concentration of residual nitrogen decreases to the level observed in adults. The amount of nitrogen excreted by the kidneys increases during the first 3 days of life, after which it decreases and again begins to increase from the 2nd week. life in parallel with the increasing amount of food.

If a congenital disorder is identified in the family, A. o. it is necessary to conduct medical genetic counseling.

Bibliography: T.T.Berezov and Korovkin B.F. Biological chemistry, p. 431, M., 1982; Veltischev Yu.E. and other Metabolism in children, p. 53, M., 1983; Dudel J. et al. Human Physiology, trans. from English, t. 1-4, M., 1985; Zilva J.F. and Pennell P.R. Clinical chemistry in diagnosis and treatment, trans. from English, p. 298, 398, M., 1988; Kon R.M. and Roy C.S. Early diagnosis of metabolic diseases, trans. from English, p. 211, M., 1986; Laboratory research methods in the clinic, ed. V.V. Menshikov, s. 222, M., 1987; Leinger A. Fundamentals of Biochemistry, trans. from English, t. 2, M., 1985; Mazurin A.V. and Vorontsov I.M. Propedeutics of childhood diseases, p. 322, M., 1985; Guide to Pediatrics, pod. ed. W.E. Berman and V.K. Vaughan, trans. from English, book. 2, p. 337, VI. 1987; Strayer L. Biochemistry, trans. from English, v. 2, p. 233, M., 1985.

Allowed
All-Russian educational and methodological center
in continuing medical and pharmaceutical education
Ministry of Health of the Russian Federation
as a textbook for medical students

To the definition of F. Engels: "Life is a way of existence of protein bodies", now we add "and nucleic acids". Numerous nitrogen-containing compounds are found in the body. We will focus on the analysis of the pathology associated with the exchange of biopolymers, which determine the basic properties of living systems: proteins and polynucleotides.

Proteins - are high-molecular compounds, consisting of 20 nonessential and essential amino acids (AA), including two functional groups NH 2 and COOH. Polynucleotides are nucleic acids and macroergs. Nitrogen-containing building blocks of polynucleotides are nitrogenous bases: purines (adenine, guanine) and pyrimidines (uracil, cytosine, thymine).

11.1. Typical changes in protein content

Hypoproteinemia - mainly due to a decrease in albumin synthesized by the liver.
Hyperproteinemia is mainly a change in the content of globulins due to an increase in gamma globulins synthesized by the plasma cells of the immune system, as well as alpha and beta globulins synthesized by the liver.
Paraproteinemia is the appearance of altered globulins. For example, in multiple myeloma, they cross the renal barrier and are identified in urine as Bens-Johnson proteins.
The result of (1) and (2) is dysproteinemia - a violation of the ratio of albumin and globulins in the blood (A / G ratio).

11.2. Pathology associated with the intake of nitrogen with food and the pathophysiological basis of medical nutrition

Proteins make up the bulk of nitrogen in food. 4 positions are important for normal balance, and therefore for pathology:

The total amount of protein entering the body.
The digestibility of these proteins.
Amino acid composition of proteins.
The total caloric content of food entering the body.

11.2.1. According to the 1st position, we can say that during the period of recovery after an illness, the need for proteins significantly exceeds the norm, equal to 0.7 g of protein / kg of body weight per day. Up to 5 years, this rate exceeds 2.0 g / kg per day. It should be noted that the body does not need nucleic acids from food. Purine and pyrimidine bases are formed in the body from AA. Nitrogenous bases supplied with food are hydrolyzed and removed.

11.2.2. According to the second position, we can say that since the amount of free amino acids in natural foods is insignificant, the value of proteins for the body is determined by its digestibility, i.e. the possibility of splitting it to AK. For example, skin proteins are not used in the human body.

11.2.2.1. Starvation

In the modern world, protein deficiency is an important nutritional problem. Families living on the brink of poverty are often low in protein even when calories are sufficient. As a rule, food rich in protein is expensive, and therefore the problem of protein deficiency acquires a social character.

Hunger and childhood

There is growing evidence that severe malnutrition in early childhood leads to stunted physical development and lifelong intellectual disability. A committee of the US Academy of Sciences, based on exhaustive scientific evidence, concluded that "severe childhood malnutrition appears to be a more important factor for later intellectual development than family and community influences."

Like the rest of the body, the human brain does not develop gradually throughout life, but mainly during the period of "growth spurt". For the brain, this is a period from 1 year (the mass of the brain is 25% of the weight of an adult brain) to 2 years (70%). If during this period the development of growth elements is slowed down, then the possibility of further development may be lost forever. This is why malnutrition during pregnancy or early childhood has the most serious consequences.

As a result of the consumption of poor in protein and inadequate calorie food, a syndrome occurs, which is called Kwashiorkor. It primarily affects infants during weaning and receiving insufficient amounts of proteins necessary for their normal development. This is possible not only in Latin America and Africa, it is just that this syndrome was first described there. In principle, using the example of Kwashiorkor, we can consider the pathogenesis of protein starvation (Fig. 23).

Violation of protein biosynthesis in the liver causes a decrease in the content of serum albumin, which leads to edema, and a decrease in the content of very low density lipoproteins (VLDL) - to the development of fatty degeneration of the liver. A decrease in Hb biosynthesis leads to the development of anemia. The function of the intestine is sharply disrupted, since the synthesis of pancreatic enzymes and the renewal of cells of the intestinal mucosa suffer from the lack of AK-precursors.

The mortality rate of such children is very high. They die from acute infections and chronic liver diseases. Undoubtedly, society should provide sufficient material assistance to those in need, and the introduction of free provision of nurseries, kindergartens, schools with milk can solve many health problems.

11.2.3. To illustrate the role of the 3rd position in pathology - the importance of the amino acid composition of proteins - we can say the following. Vegetable proteins (for example, bread) are less valuable in amino acid composition than animals. The reason is the relatively low content of some essential AA in them. Corn is poor in tryptophan and lysozyme, legumes are poor in methionine.

Since the need for AA in humans is usually covered by food proteins, the development of a phenomenon associated with a deficiency of any one AA is unlikely. With a pathological condition, this becomes possible. For example, in healthy people, up to 1% of tryptophan is used to form serotonin.

Now two examples from pathology:

In patients with malignant intestinal carcinosis, the amount of tryptophan used for the synthesis of this amine reaches 60%, which leads to a relative deficiency of tryptophan and the development of cataracts, atrophy of the testes, hyperplasia of the gastric mucosa;
on the other hand, the introduction of sulfur-containing AAs (cysteine, methionine) into the body accelerates wound healing.

The question of the biological role of individual amino acids in the diet of a sick person has not yet been fully developed. The expanded clinical use of AA for parenteral nutrition makes it necessary to study this issue.

Optimality of nutrition also depends on the second, still unresolved, problem of the balance of amino acids necessary to maintain nitrogen balance in an adult.

11.3. Nitrogen balance

Positive nitrogen balance, i.e. the accumulation of nitrogen in the body occurs in physiological and pathological conditions, accompanied by an increase in the biosynthesis of proteins and nucleotides. For example, during the period of convalescence after an illness.

Negative nitrogen balance - a decrease in the amount of nitrogen in the body, noted during complete or incomplete fasting, debilitating diseases, and fever. Tissue proteins are intensively broken down into individual AAs, which are used to provide the body's energy requirements through gluconeogenesis. In this case, more nitrogen is removed than supplied.

Nitrogen balance - the amount of nitrogen consumed exactly matches the amount of nitrogen excreted from the body. Nitrogen is used for syntheses. The half-life of proteins in the whole organism is 3 weeks, i.e. every 3 weeks we renew ourselves by half. In this case, the rate of protein biosynthesis is up to 500 g / day, i.e. almost 5 times the amount of protein consumed with food. Where does nitrogen come from? For this, the decay products of protein tissues are used.

11.4. The role of the liver in nitrogen metabolism

As with many other metabolic processes, the liver plays a key role in the conversion of AA. This is due to the fact that hepatocytes have a full set of amino acid metabolism enzymes (Fig. 24).

11.4.1. Enhanced protein breakdown

This is a typical form of protein metabolism disorder. Currently, protein metabolism is considered as a dynamic process, during which the body's proteins are constantly renewed, i.e. are continuously synthesized and degraded.

The half-life of whey proteins exported by the liver is about 3 weeks. The factor that regulates the breakdown of intracellular proteins is proteolysis by lysosomal enzymes. We talked about these enzymes in detail in the chapter on inflammation. Returning to the chapter, you will recall that in a pathological condition, the permeability of lysosomal membranes is disturbed and lysosomal enzymes enter the cell, causing the disintegration of its protein structures. Let me remind you that normally lysosomes carry out the destruction of proteins within themselves, capturing denatured proteins by pinocytosis.

I think that it is already obvious to you that damage to membrane lysosomes occurs not only in the liver, but also in any other organs, and not only during inflammation, but also as a result of the action of other factors: ultrasound, radiation, hypoxia, fasting in the postoperative period, etc. .d. Thus, enhanced protein breakdown as a typical form of protein metabolism disorder is always associated with lysosomal proteases.

11.4.2. Protein synthesis

Each type of cells from the general pool of amino acids forms its own individual proteins. Muscle cells - actin and myosin; osteoblasts and connective tissue cells - collagen; hepatocytes are their own proteins and most of the plasma proteins.

Violation of protein synthesis, on the one hand, is associated with a hereditary violation of the activity of amino acid metabolism enzymes, i.e. with DNA point mutations. You will find these sections of the pathology of protein metabolism in the chapter "Pathology of heredity" and, in addition, they are described in sufficient detail in the textbook edited by AD Ado and VV Novitsky in the section "Disorders of amino acid metabolism".

On the other hand, the pathology of protein biosynthesis occurs when the membranes of the endoplasmic reticulum are damaged, where protein molecules are synthesized on the ribosomes. The most characteristic and frequent parenchymal liver disease is hepatitis, the basis of the pathogenesis of which is damage to the subcellular structures of hepatocytes.

The clinical manifestation of hepatitis is a decrease in the level of many plasma proteins. It is known that the overwhelming amount of these proteins is synthesized by the liver. These include: albumin, fibrinogen, prothrombin. The most sensitive indicator is a low level of enzymes in the blood, for example, butyrylcholinesterase synthesized by the liver.

A number of reasons for the change in the amount of blood proteins are not associated with the biosynthesis of proteins by the liver. For example, hypoalbuminemia with increased permeability of the membranes of the bloodstream cells.

11.4.2.1. Parenteral nutrition and plasma proteins

If necessary, replenishment of blood reserves resort to the introduction into the patient's bloodstream of blood plasma containing various proteins. But now you understand that, since in order for the body to use these proteins, they still have to be destroyed to AA, the most valuable is the use of ready-made mixtures of the latter. Parenteral administration of AA can maintain nitrogen balance in patients with protein-free nutrition, and even a positive nitrogen balance can be achieved (nutrition of cancer patients, patients in the postoperative period).

11.4.2.2. Pathology associated with the regulation of protein biosynthesis

If the processes of protein breakdown are associated with the unregulated activity of lysosomal enzymes, then the biosynthesis of proteins is controlled by the endocrine system and, above all, by STH (somatotropic hormone). The introduction of STH increases the biosynthesis of proteins by increasing the synthesis of mRNA, increasing the permeability of cell membranes for amino acids. Therefore, hyperfunction of STH leads to an increase in the growth of new cells and gigantism, and a deficiency leads to dwarfism (pituitary dwarfism).

Excessive formation of ACTH increases the synthesis of steroid hormones, which lead to suppression of protein biosynthesis and the switch of AA to gluconeogenesis. This is understandable, since steroid hormones are hormones of stressful situations and when energy is needed to fight for survival, biosynthesis has to be delayed. That is why a negative nitrogen balance is observed with prolonged stress-effects, tumors of the adrenal cortex.

Enhances protein biosynthesis and insulin. Therefore, in diabetes mellitus, characterized by a relative or absolute lack of insulin, the biosynthesis of proteins decreases. Frequent pustular diseases in diabetes mellitus are obviously associated with the suppression of the formation of antibody proteins, other protein factors of nonspecific and specific anti-infectious defense.

11.4.3. Pathology of amino acid interconversion

The purpose of the interconversion of AA is to maintain nitrogen homeostasis, preserving it for the synthesis of nonessential amino acids. The main role in these processes is played by transamination reactions catalyzed by aminotransferases (AT). Their mechanism of action is the transfer of the amino group. Vitamin B6 is the mediator.

The reaction proceeds in any direction and depends on the ratio of the concentration of the reacting components. Thus, if the concentration of AK-2 is low, while AK-1 and keto acid-2 are supplied in abundance from food or from tissues, then the transfer of the amino group will go from left to right and vice versa. In each case, a participant in these reactions is alpha-KG, which accepts an amino group from AAs that are in abundance and gives it up for the formation of those AAs whose insufficiency threatens the body.

11.4.3.1. What is the essence of switching protein metabolism to gluconeogenesis under the influence of GCS?

It takes place in two stages:

GCS due to induction (biosynthesis de novo) significantly increase the activity of aminotransferases (AT), while during transamination there is an increase in the formation of pyruvate (see above).
GCS increase the activity of gluconeogenesis enzymes in the same way, which catalyze the formation of glucose from pyruvate.

11.4.3.2. Diagnostic value of aminotransferases

Damage to the outer membranes of cells of various tissues is accompanied by the release of AT from the cytoplasm of cells into the blood. So, in acute hepatitis, the activity of AT increases up to 100 times against the norm. But since AT is present in the cells of any tissue, an increase in AT in the blood is noted with damage to the myocardium, kidneys, etc.

11.4.4. Ammonia exchange

The exchange of ammonia is extremely important, since free inorganic ammonia is extremely toxic (it binds with alpha-KG, forming glutamate, thereby diverting the substrate from the TCA, which is manifested in a decrease in the formation of ATP). Like any homeostasis constant, the ammonia content is an equilibrium constant, i.e. depends on the rate of its formation and utilization.

The source of ammonia in tissues is amino acids, nitrogenous bases. The main source is the oxidation of the amino acid glutamate by glutamate dehydrogenase. This enzyme catalyzes the release of AA from the amino group in the form of ammonia by the oxidative deamination reaction. The second product of the reaction is the CTK substrate, alpha-KG.

11.4.4.1. Disposal of ammonia and textiles

It distinguishes between three main processes:

The reductive amination reaction is the reverse deamination reaction and is catalyzed by the same GDH. With the help of this reaction of the addition of an amino group to alpha-KG, ammonia is absorbed, which is formed as a result of the action of bacteria in the gastrointestinal tract. With an excess of ammonia, depletion of alpha-KG reserves and inhibition of the CTC can occur.
Glutamine formation. It is a form of ammonia deposition and transport involved in maintaining the intracellular ammonia concentration at a level that does not reach the toxicity limits. The reaction is catalyzed by glutamine synthetase. The importance of this reaction is especially clearly seen in stress reactions, accompanied by the stimulation of gluconeogenesis. Ammonia formed during the metabolism of proteins and amino acids, already in the form of glutamine, is transported from such massive peripheral tissues as muscle tissue with blood flow to the liver. In the liver, under the influence of glutaminase, ammonia is cleaved from glutamine.
The third way of ammonia metabolism (85-88%) is the synthesis of carbamoyl phosphate, through which it enters the urea cycle, an absolutely harmless organic compound.

Unlike the 1st and 2nd pathways of ammonia fixation, the formation of urea occurs only in the liver. The reason for this is that carbamoyl phosphate synthetase and two other enzymes of the urea cycle (ornithinecarbamoyltransferase and arginase) are found only in liver mitochondria.

The urea cycle is clearly depicted in a textbook edited by A.D. Ado and V.V. Novitsky. We will dwell in more detail on the pathology associated with violations in the urea cycle.

11.4.4.2. Diagnostics and clinic of disorders of the urea cycle

The detection of enzymes of the urea cycle in the blood is of great diagnostic value, as it indicates liver damage. After all, carbamoyl phosphate synthetase, ornithinecarbamoyl transferase and arginase are localized exclusively in the mitochondria of hepatocytes.
The clinical manifestation is hepatic coma. One of the most formidable manifestations of liver damage is the development of severe attacks, accompanied by loss of consciousness as a result of damage to the central nervous system (hepatic coma). Liver disorders in acute hepatitis are based on damage to hepatocytes (CCl 4 poisoning and other poisons). Many hepatotropic substances increase lipid peroxidation, causing damage to membranes, including mitochondria. If a significant amount of parenchyma is turned off, damage to mitochondria leads to impaired utilization of ammonia, which is formed in tissues and comes from the intestine as a result of the action of bacteria.

In many cases, in chronic liver diseases, damage to the parenchymal organ is accompanied by the proliferation of connective tissue and impaired blood flow, which normally accounts for 1/4 of all blood flowing from the heart. As a result of obturation of the v.porta system, collaterals develop, flowing directly into the inferior vena cava bypassing the liver. Through such a port-caval shunt, substances absorbed in the gastrointestinal tract enter the tissues directly, aggravating the consequences, disrupting the neutralization of ammonia formed in the tissues and bacteria of the digestive tract.

Thus, the liver does not detoxify ammonia and other waste products of intestinal bacteria entering the liver (indole, skatole, putrescine). An excess of ammonia and other toxic compounds in the blood causes both a direct damaging effect associated with its lipotropy and inclusion in biomembranes, and inhibition of the tricarboxylic acid cycle. Confusion and loss of consciousness are caused by the nervous system being most sensitive to excess ammonia due to the high ATP requirement.

Hepatic coma treatment. Coma attacks can only be alleviated by increasing the activity of the starting stage of the urea cycle by introducing the cofactor of the carbamoyl phosphate synthetase reaction in the liver. This substance is N-carbamoylglutamine. In especially severe cases, hemodialysis, exchange blood transfusion or hemosorption, temporary connection of a foreign liver is necessary.

11.5. Pathology of exchange of nitrogenous bases

Nitrogen-containing cyclic compounds are the most important complex of RNA and DNA nucleotides, nucleotide coenzymes NAD, NADP, FMN, macroergs ATP, GTP, UTP. Satisfaction of the organism with them occurs mainly not due to their intake with food (protection of the gene pool), but due to their complete biosynthesis from amino acids and carbohydrates. Two main places of formation of nitrogenous bases: liver, intensively proliferating tissues (hematopoietic).

Now about the decay of nitrogenous bases.

The cyclic structures of pyrimidines are completely destroyed, but there are no enzymes in the body to break the purine rings. Their destruction is stopped at the stage of formation of uric acid from xanthine, catalyzed by xanthine oxidase. Therefore, excess purines are excreted from the body intact in the form of uric acid.

In the liver, purine bases undergo deamination to form xanthine. Further oxidation to form uric acid is catalyzed by the liver enzyme xanthine oxidase, since uric acid can neither be reused nor decomposed further. In this regard, this compound is similar to urea, the end product of ammonia protein metabolism. Both of these end products are excreted in the urine, so the uric acid content is indicative of nucleic acid catabolism in the body.

11.5.1. Gout

Gout is a purine metabolism abnormality (Fig. 25). It is a syndrome characterized by excess uric acid in the blood (hyperuricemia), arthritis and usually accompanied by kidney damage. The reason is unknown. The basis of pathogenesis is the deposition of sodium urate crystals in the tissues of the joints and kidneys. Over time, these deposits turn into nodes (toffs) visible even with the naked eye in the joints of the limbs and into stones of the urinary tract.

The pathochemistry of disorders of purine metabolism in general terms is as follows: even normally, the concentration of uric acid salts in body fluids is close to the state of saturation. In the blood of patients with gout, urates form an already oversaturated solution. It is stabilized by blood proteins, but any local decrease in pH (in the kidneys - the release of acid metabolites, some drugs) leads to the appearance of foci of crystallization.

Treatment. Pathogenetically justified is the use in the treatment of such patients allopurinol, a xanthine oxidase inhibitor, which reduces the formation of uric acid and probetsid, which enhances the excretion of uric acid by the kidneys. Diet is an important component of treatment. A natural requirement for gout is a low intake of foods rich in purines, such as meat. At the same time, such valuable food products as eggs and dairy products are low in purines.

I. Study purpose: know end products of protein metabolism in the body, the main sources of ammonia formation, ways of its neutralization from the body.

II. Be able toquantitatively determine the content of urea by the color reaction with diacetyl monooxime in blood serum; get acquainted with the physical and chemical properties of urea.

III. Initial level of knowledge:qualitative reactions to ammonia (inorganic chemistry).

IV. To answer to the questions of the final control tickets on the topic: “The breakdown of simple proteins. Amino acid metabolism, end products of nitrogen metabolism ”.

1. The end products of the breakdown of nitrogen-containing substances are carbon dioxide, water and ammonia, in contrast to carbohydrates and lipids. The source of ammonia in the body are amino acids, nitrogenous bases, amines. Ammonia is formed as a result of direct and indirect deamination of amino acids, (the main source) of hydrolytic deamination of nitrogenous bases, inactivation of biogenic amines.

2. Ammonia is toxic and its action is manifested in several functional systems: a) easily penetrating through membranes (disrupting the transmembrane transfer of Na + and K +) in mitochondria, it binds to α-ketoglutarate and other keto acids (CTA), forming amino acids; reduction equivalents (NADH + H +) are also used in these processes.

b) at high concentrations of ammonia, glutamate and aspartate form amides, using ATP and disrupting the same TCA, which is the main energy source of the brain. c) The accumulation of glutamate in the brain increases osmotic pressure, which leads to the development of edema. d) An increase in the concentration of ammonia in the blood (N - 0.4 - 0.7 mg / l) shifts the pH to the alkaline side, increasing the affinity of O 2 to hemoglobin, which causes hypoxia of the nervous tissue. e) A decrease in the concentration of α-ketoglutarate causes inhibition of amino acid metabolism (synthesis of neurotransmitters), acceleration of the synthesis of oxaloacetate from pyruvate, which is associated with increased use of CO 2.

3. Hyperammonemia primarily has a negative effect on the brain and is accompanied by nausea, dizziness, loss of consciousness, mental retardation (in chronic form).

4. The main reaction of ammonia binding in all cells is the synthesis of glutamine under the action of glutamine synthetase in mitochondria, where ATP is used for this purpose. Glutamine is diffused into the bloodstream and transported to the intestines and kidneys. In the intestine, glutaminase forms glutamate, which is transaminated with pyruvate, converting it into alanine, which is absorbed by the liver; 5% of ammonia is removed through the intestines, the remaining 90% is excreted by the kidneys.

5. The kidneys also undergo hydrolysis of glutamine with the formation of ammonia under the action of glutaminase, which is activated by acidosis. In the lumen of the tubules, ammonia neutralizes acidic metabolic products forming ammonium salts for excretion, while reducing the loss of K + and Na +. (N - 0.5 g of ammonium salts per day).

6. The high level of glutamine in the blood causes its use in many anabolic reactions as a nitrogen donor (synthesis of nitrogenous bases, etc.)

7. The most significant amounts of ammonia are rendered harmless in the liver by urea synthesis (86% of nitrogen in urine) in an amount of ~ 25 g / day. Urea biosynthesis is a cyclic process where the key substance is ornithine, attaching carbomoyl formed from NH 3 and CO 2 upon activation of 2ATP. Formed citrulline in mitochondria is transported to the cytosol for the introduction of a second nitrogen atom from aspartate to form arginine. Arginine is hydrolyzed by arginase and converted back to ornithine, and the second product of hydrolysis is urea, which in fact in this cycle was formed from two nitrogen atoms (sources –NH 3 and aspartate) and one carbon atom (from CO 2). Energy is provided by 3ATP (2-in the formation of carbomol phosphate and 1 in the formation of argininosuccinate).

8. The ornithine cycle is closely related to the TCA, because aspartate is formed during the transamination of ANA from the CTA, and the fumarate remaining from aspartate after the removal of NH 3 returns to the CTA and, when it is converted into ANA, 3 ATPs are formed, providing the biosynthesis of the urea molecule.

9. Hereditary disorders of the ornithine cycle (citrullinemia, argininosuccinaturia, hyperargininemia) lead to hyperamminemia and in severe cases can lead to hepatic coma.

10. The rate of urea in the blood is 2.5-8.3 mmol / l. A decrease is observed in liver diseases, an increase is the result of renal failure.

Laboratory work