Download 12. Metabolism of nucleoproteins

NUCLEOPROTEINS
METABOLISM
Nucleases (DNA-аse і RNAase) decompose nucleoproteins
to oligonucletides
Oligonucleotide
Phosphodiesterases decompose oligonucleotides to
mononucleotides
Nucleotides
structure
Nucleotidases –
split off
phosphoric
acid with
the
formation
of
nucleosides
Nucleosidases
decompose
nucleosides to
nitrogenous base and
pentose
Nitrogenous bases
DECOMPOSITION OF MONONUCLEOTIDE
NH 2
Phosphatases
N
N
OH
N
N
O P O CH2
Nucleosidases
O
OH
H
H
H
OH
OH
H
Adenosine mononucleotide
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
+ Pentose
bases
DESTINY OF NITROGENOUS BASES, PENTOSES AND
PHOSPHORIC ACIDS IN THE ORGANISM
Nitrogenous
bases
oxidation to the end products
Pentoses
oxidation with energy formation;
synthesis of nucleotided;
synthesis of hexoses;
synthesis of coenzymes
Phosphoric acid
phosphorilation;
ATP synthesis;
synthesis of phospholipids;
buffer systems;
constituent of bones, cartilages
Catabolism of purine
nucleotides
Catabolism
of purine
nucleotides
Xanthine
oxidase
Uric acid
formation
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:
accumulation 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
H
C
Aspartate
Formil-H4folate
N
HC
1
2
6
3
N
Glycine
N
5
4
C
7
C
9
N
H
R
Glutamine
8
CH
Methenil-H4folate
Synthesis of Purine
Nucleotides
Ribosephosphate is formed in pentosephosphate pathway from glucose
Purine ring is synthesized on ribose-5phosphate 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)
NH2
Disintegration
of
pyrimidine
nucleotides
NH2
N
N
O
N
H
Цитозин
cytosine
1
/2O2
O
Тимін
thimine
NH3
NADPH + H+
O
dehydrogenase
HN
O
NADP+
N
H
Урацил
uracile
dehydrogenase
O
NADPH + H+
NADP+
O
H
H
H
H
O
N
H
Дигідротимі
dihydrothimineн
COO–
hydrolase
N
H
Дигідроурацил
dihydrouracile
H2O
NH2
CH2
C
CH2
O
N
H
COO–
H3N
CH2 CH2
NH2
H2O
–
COO
C
CH3
H
C
H2O
-Аланін
-alanine
H2O
hydrolase
-Уреїдопропіонат
N-carbomoil
-alanine
(N-карбамоїл--аланін)
+
CH3
H
H
H
HN
O
HN
N
H
hydrolase
CH2
N
O
H
-Уреїдоізобутират
N-carbomoil (N-карбамоїлaminoisobutirate
-аміноізобутират)
O2
CH3COO–
CO2 + NH3
H3N+
CH2 CH
COO–
CH3
-Аміноізобутират
-aminoisobutirate
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 orotatephosphoribosyltransferase 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