1. NUCLEOPROTEINS METABOLISM

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

4. Oligonucleotide

5. Nucleotides structure
Phosphodiesterases decompose oligonucleotides to mononucleotides
Nucleotides structure

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

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

8. DECOMPOSITION OF MONONUCLEOTIDE
Adenosine mononucleotide
Phosphatases
Nucleosidases

9. 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
Mononucleotides
Phosphodiesterases
Nuclesides
Phosphoric acid +
Phosphatases
Nitrogenous bases
Pentose
Nucleosidases

10. DESTINY OF NITROGENOUS BASES, PENTOSES AND PHOSPHORIC ACIDS IN THE ORGANISM
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

11. Catabolism of purine nucleotides

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

13. 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

14. 0.5-1 g of uric acid is formed daily in the organism
Normal concentration – 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)

15. 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.

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

17. Gout: accumulation of uric acid salts in joints

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

19. Gout: kidney stones.

20. 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

21. Lesch-Nyhan syndrom:
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)

22. Treatment: allopurinol – competitive inhibitor of xanthine oxidase

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

24. 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.

25. 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 (in the out-of-liver tissues)

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

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

28. SYNTHESIS OF PYRIMIDINE NUCLEOTIDES

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

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