Biosynthesis and catabolism of purine nucleotides. Determination of the end products of their metabolism.

Biosynthesis and catabolism of purine nucleotides.

Determination of the end products of their metabolism

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

Nucleotides structure

Phosphodiesterases decompose oligonucleotides to mononucleotides

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

Nitrogenous bases

Nucleosidases decompose nuclesides to nitrogenous base and pentose

HH

OH OH

H H

O

N

N N

N

NH2

CH2OP

OH

OH

O

Adenosine mononucleotide

Phosphatases

Nucleosidases

DECOMPOSITION OF MONONUCLEOTIDE

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

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

Catabolism of purine nucleotides

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

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

Treatment: allopurinol – competitive inhibitor of xanthine oxidase

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

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)