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NUCLEOPROTEINS METABOLISM

NUCLEOPROTEINS METABOLISM. Nucleases ( DNA -а se і RNA - ase ) decompose nucleoproteins to oligonucletides. Oligonucleotide. Phosphodiesterases decompose oligonucleotides to mononucleotides. Nucleotides structure.

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NUCLEOPROTEINS METABOLISM

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  1. NUCLEOPROTEINS METABOLISM

  2. Nucleases (DNA-аse і RNA-ase) decompose nucleoproteins to oligonucletides

  3. Oligonucleotide

  4. Phosphodiesterases decompose oligonucleotides to mononucleotides Nucleotides structure

  5. Nucleoti-dases – split off phosphoric acid with the formation of nucleosides

  6. Nucleosidases decompose nucleosides to nitrogenous base and pentose Nitrogenous bases

  7. Phosphatases Nucleosidases Adenosine mononucleotide DECOMPOSITION OF MONONUCLEOTIDE

  8. DECOMPOSITION OF NUCLEIC ACIDS IN INTESTINE AND TISSUE Nucleoproteins (nucleic acids + proteins) Pepsin, gastricsin, HCl Nucleic acids + Histones, protamines Nucleases (DNA-ases, RNA-ases) Oligonucleotides Phosphodiesterases Mononucleotides Phosphatases Nuclesides + Phosphoric acid Nucleosidases Nitrogenous bases + Pentose

  9. DESTINY OF NITROGENOUS BASES, PENTOSES AND PHOSPHORIC ACIDS IN THE ORGANISM Nitrogenous bases oxidation to the end products oxidation with energy formation; synthesis of nucleotided; synthesis of hexoses; synthesis of coenzymes Pentoses phosphorilation; ATP synthesis; synthesis of phospholipids; buffer systems; constituent of bones, cartilages Phosphoric acid

  10. Catabolism of purine nucleotides

  11. Catabolism of purine nucleotides Uric acid formation Xanthine oxidase Xanthine oxidase Uric acid

  12. ГОРБАЧЕВСЬКИЙ Іван Якович – біохімік, громад. та політ. діяч. В вперше синтезував сечову кислоту й довів, що в живих істотах вона утворюється з нуклеїнових кислот, відкрив фермент ксантиноксидазу, розробив методи визначення білків і пуринових основ. ГОРБАЧЕВСЬКИЙ Іван Якович сечова кислота

  13. 0.5-1 gof uric acid is formed daily in the organism Normal concentration– 0.2-0.5 mmol/L Uric acid – poorly soluble in water Hyperuricemia: -inherited (primary), -gained (secondary). Secondary: in radiation injury, blood diseases, tumors, toxemia, kidney diseases, alimentary (hyperconsumption of meat, coffee, tea)

  14. Gout – inherited disease accompanied with hyperuricemia and crystallization of uric acid and its salts in joints, cartilages and kidneys. Symptoms: -joints inflammation, acute pain -renal stones -tophuses.

  15. Gout: accumula-tion of uric acid salts in joints

  16. Gout: accumulation of uric acid salts in joints

  17. Gout: tophuses – accumulation of uric acid salts in cartilages, under skin.

  18. Gout: kidney stones.

  19. Lesch-Nyhan Syndrom: is a inherited disorder caused by a deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase. LNS is present at birth in baby boys. Hypoxanthine and guanine are not used in the salvage pathway of purine nucleotides synthesis. Hypoxanthine and guanine are not utilizied repeatedly but converted into uric acid. Symptoms: - severe gout -severe mental and physical problems - self-mutilating behaviors

  20. Lesch-Nyhansyndrom: • gout-like swelling in some joints • kidney and bladder stones • delayed motor development • bizarre • sinuous movements • increased deep tendon reflexes • self-destructive behavior (chewing off fingertips and lips)

  21. Treatment: allopurinol – competitive inhibitor of xanthine oxidase

  22. Synthesis of purine bases Origin of atoms in purine molecule CO2 Glycine Aspartate Methenil-H4-folate Formil-H4-folate Glutamine

  23. Synthesis of Purine Nucleotides Ribosephosphate is formed in pentose-phosphate pathway from glucose Purine ring is synthesized on ribose-5-phosphate by the way of gradual adding of nitrogen and carbon atoms and cyclization. The way of biosynthesis consist of 11 reactions.

  24. Synthesis of Purine Nucleotides Two ways of biosynthesis: -de novo – formation of purine nucleotides from simple acyclic precursors (in liver) -salvage (reserve) pathway – using of purine bases formed in the decomposition of nucleotides (inthe out-of-liver tissues)

  25. cytosine thimine dehydrogenase uracile dehydrogenase dihydrothimine hydrolase hydrolase dihydrouracile N-carbomoil -alanine -alanine N-carbomoil -aminoisobutirate hydrolase -aminoisobutirate Dis-integ-ration of pyri-midine nucle-otides

  26. SYNTHESIS OF PYRIMIDINE NUCLEOTIDES Origin of atoms in pyrimidine molecule

  27. SYNTHESIS OF PYRIMIDINE NUCLEOTIDES

  28. OROTACIDURIA inherited disorder of pyrimidine synthesis caused by a deficiency of the enzyme of orotate-phosphoribosyltransferase anddecarboxylase. Symptoms: –excess of orotic acid and its excretion with urine (1.0-1.5 g) -mental and physical retardation -megaloblastic anemia

  29. TREATMENT OF OROTACIDURIA Taking of uridin during the whole life

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