‫بسم هللا الرحمن الرحيم‬

Nucleotide metabolism
 Functions of neucleotides
 Precursors for RNA and DNA synthesis
 Energy substance in body (ATP)
 Physiological Mediators (cAMP)
 Components of coenzymes (NAD+)
 Allosteric effectors and donor of
phosphate group (phosphorylation)
 Formation of activated intermediates

UDP-glucose, CDP-choline
Nucleotide Synthesis
and Degradation
 Digestion and absorption of nucleotide
Nucleoprotein

Protein Nucleic acid

Nucleases
Nucleotide
Nucleotidase
Absorption
Phosphate Nucleoside Blood
Nucleosidase

Base Ribose
There are two basic mechanisms to
generate purines and pyrimidines

1. DE NOVO BIOSYNTHETIC PATHWAYS

(building the bases from simple building
blocks)

2. SALVAGE PATHWAYS
(the reutilization of bases from dietary
or catabolic sources)
Metabolism of Purine nucleotides
 Biosynthesis of purine nucleotides
de novo synthesis( synthesis of complex molecules from simple
molecules such as sugars or amino acids)
salvage pathway  nucleotides (purine and pyrimidine) are synthesized
from intermediates in the degradative pathway for nucleotides

AMP GMP
1.De novo synthesis of purine nucleotides
CO2 Glycine

Aspartate
One
One carbon
carbon unit
unit

Glutamine
 Characteristics of de novo synthesis of
purine nucleotides
1. in cytosol
2. form IMP first, then synthesize AMP
and GMP from IMP.
3. formation of purines is
based on the ribosyl
group of 5’-phosphoribose
 （ 5’-phosphoribose 1’- AMP ATP R-5-P
pyrophosphate, PRPP ）
PRPPK （ ribose5’-phosphosphate ）

Gln
Glutamine PRPP
amidotransferase Glu
(GPRT)

（ 5´-phosphoribosyl-amine ）

AMP

IMP
GMP
 Regulation of de novo synthesis of purine
nucleotides
_ _
_
+
Adenyl-
+ succinate
AMP ADP ATP
R-5-P PRPPK GPAT
PRPP _PRA IMP
ATP _ XMP GMP GDP GTP

_
Adenyl-
GTP succinate AMP ADP ATP
+
IMP
XMP +
GMP GDP GTP
_ATP
 2. Salvage synthesis of purine
nucleotides
 Material:

PRPP, purine
or
nucleosides (phosphorylation)

 Location:

brain and bone marrow

 APRT
adenine+ PRPP AMP + PPi
HGPRT
hypoxanthine+PRPP IMP + PPi

HGPRT
guanine+ PRPP GMP + PPi

Adenylate kinase
adenosine AMP
ATP ADP

APRT: adenine phosphoribosyltransferase

HGPRT: hypoxanthine-guanine
phosphoribosyltransferase
Degradation of purine nucleotides
nucleotides
Nucleotidase
nucleosides
Nucleoside phosphorylase

ribose-1-phosphate purine

salvage pathway uric acid

 IMP

Neucleo
-tidase

Excretion
Metabolism of pyrimidine nucleotides
 Biosynthesisof pyrimidine nucleotides
de novo synthesis
salvage pathway
1.De novo synthesis of pyrimidine
nucleotides

4
Glutamine 3 5
Aspartate
CO2 2 6
1
 Characteristics of de novo synthesis of
pyrimidine nucleotides
1. mostly in cytosol
2. form UMP first, then synthesize other
pyrimidine nucleotides from UMP.
3. in the synthesis of UMP, pyrimidine
ring is formed first , then combined with
PRPP.
 Process of de novo synthesis of UMP
 1. formation of Carbamoyl phsphate (CP)
CO2 + glutamine + H2O + 2ATP

Carbamoyl phosphate
synthaseⅡ (CPSⅡ)
O
H 2N C O ~ PO32- + 2ADP + Pi
carbamoyl phosphate
 The different between Carbamoyl
氨基甲酰磷酸合成酶 phosphate
I、II 的区别
synthaseⅠ,Ⅱ(CPS Ⅰ,Ⅱ)

CPS-I CPS-II

Location Mitochondria of cytosol of all

分布 肝细胞线粒体中
liver cells 胞液
cells（ 所有细胞）
氮源 of
Source 氨3
NH 谷氨酰胺
Glutamine
nitrogen
变构激活剂 N-乙酰谷氨酸
N-acetylglutamate 无
None
Activator
功能
Function 尿素合成
Formation of urea Formation
嘧啶 合成of
pyrimidine
2. Formation of UMP
O
H2N C O ~ PO32- +
carbamoyl phosphate Aspartate

Carbamoyl aspartate

Orotate
PRPP

UMP
 3. Synthesis of CTP, dTMP or TMP

CTP
UMPK NDK synthase
UDP UTP
ATP ADP Gln
ATP ADP Glu
ATP ADP

dUDP
dCMP
dTMP
dUMP

TMP synthase
Regulation of de novo synthesis
of pyrimidine nucleotides
ATP + CO2+ glutamine 1. Activated by
+
substrates
Carbamoyl phosphate
2. Inhibited by products
-
aspartate
-
Carbamoyl aspartate Purine nucleotides
+ -
PRPP ATP + 5-phosphate ribose
UMP - Pyrimidine nucleotides

UTP CTP
-
Salvage pathway of pyrimidine nucleotides

Uracil phosphate
ribosyltransferase
Uracil + PRPP UMP + PPi

Uridine
phosphorylase
Uracil + 1-phosphoribose Uridine + Pi

Uridine kinase
Uridine + ATP UMP +ADP
Degradation of pyrimidine nucleotides
nucleotide
Nucleotidase
nucleosides
Nucleoside phosphorylase

phosphoribose pyrimidine
 Cytosine Thymine
NH3

Uracil

β-ureidoisobutyrate
dihydrouracil
H2 O H2 O

+ CO2 + NH3 +
β-alanine β-aminoisobutyrate
liver
Excreted
Acetyl CoA in urine
Urea Succinyl
CoA
TAC
TAC Glucose