NUCLEOPROTEINS METABOLISM

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

Oligonucleotide

Nucleotides structure Phosphodiesterases decompose oligonucleotides to mononucleotides Nucleotides structure

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

Nucleosidases decompose nucleosides to nitrogenous base and pentose Nitrogenous bases

DECOMPOSITION OF MONONUCLEOTIDE Adenosine mononucleotide Phosphatases Nucleosidases

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

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

Catabolism of purine nucleotides

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

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

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)

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.

Gout: accumula-tion of uric acid salts in joints

Gout: accumulation of uric acid salts in joints

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

Gout: kidney stones.

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

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)

Treatment: allopurinol – competitive inhibitor of xanthine oxidase

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

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.

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)

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

SYNTHESIS OF PYRIMIDINE NUCLEOTIDES Origin of atoms in pyrimidine molecule

SYNTHESIS OF PYRIMIDINE NUCLEOTIDES

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 (1.0-1.5 g) -mental and physical retardation -megaloblastic anemia

TREATMENT OF OROTACIDURIA Taking of uridin during the whole life