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Biosynthesis and catabolism of purine nucleotides.
Determination of the end products of their metabolism
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Nucleases (DNA-аse і RNA-ase) decompose nucleoproteins to oligonucletides
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Nucleotides structure
Phosphodiesterases decompose oligonucleotides to mononucleotides
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Nucleoti-dases – split off phosphoric acid with the formation of nucleosides
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Nitrogenous bases
Nucleosidases decompose nuclesides to nitrogenous base and pentose
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HH
OH OH
H H
O
N
N N
N
NH2
CH2OP
OH
OH
O
Adenosine mononucleotide
Phosphatases
Nucleosidases
DECOMPOSITION OF MONONUCLEOTIDE
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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
DECOMPOSITION OF NUCLEIC ACIDS IN INTESTINE AND TISSUE
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Phosphoric acid
Nitrogenous bases
Pentoses
phosphorilation; ATP synthesis; synthesis of phospholipids; buffer systems; constituent of bones, cartilages
oxidation with energy formation; synthesis of nucleotided; synthesis of hexoses; synthesis of coenzymes
oxidation to the end products
DESTINY OF NITROGENOUS BASES, PENTOSES AND PHOSPHORIC ACIDS IN THE ORGANISM
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Catabolism of purine nucleotides
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N
N
NH2
N
N
Рибозофосфат
N
N
OH
NH
N
N
N
OH
N
N
N
N
OH
NH
N
АМФ Гіпоксантин
H2N HO
Рибозофосфат
ГМФ
Ксантин
HN
NH
O
O NH
HN
ON
N
OH
HO NH
NOH
Catabolism of purine nucleotides
Uric acid formation
Сечова кислота
Xanthine oxidase
Xanthine oxidase
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0.5-1 g of 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)
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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.
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Gout: accumula-tion of uric acid salts in joints
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Gout: accumulation of uric acid salts in joints
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Gout: tophuses – accumulation of uric acid salts in cartilages, under skin.
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Gout: kidney stones.
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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
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Treatment: allopurinol – competitive inhibitor of xanthine oxidase
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Origin of atoms in purine molecule
Synthesis of purine bases
N
H CN
C
C
HC
NH
C HN
R
1
23
4
56 7
9
8
Glutamine
Methenil-H4-folate
Glycine
CO2
Aspartate
Formil-H4-folate
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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.
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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)