De no vo and Salvage pathway of nucleotide synthesis
There are two principal routes for the synthesis of nucleotides: the novo and the salvage
pathways. Using 5-phosphoribosyl-1 -pyrophosphate (PRPP), the de novo pathway enzymes
build purine and pyrimidine nucleotides from "scratch" using simple molecules such as C02,
amino acids and tetrahydrofolate. This route of nucleotide synthesis has a high requirement
for energy as compared that of the salvage pathway. For example, five of the 12 steps of de
novo puine synthesis require hydrolysis of ATP or GTP but only one salvage cycle reaction
uses ATP. The enzymes of both of these biosynthetic routes are classified as "housekeeping"
enzymes because they perform basic, cellular activities and are ass umed to be present in low.
constitutive levels in all cells.
Purine biosynthesis de novo pathway
Aibose-5-phosphate
ATP
AMP
Sphosphoriboyl yroçhosphate
Glutamine
Gutamate
HP,O,
S-phosphoritbosy amine pyrophosphate
ATPglycine -Glutamine +ATP
ADP Glutamate + ADP
Aspartate + ATP
ADP
Fumarate
GTPaspartate Inosinic acid
GDP
Adenylosuccinate Xanthyllc acid
Glutamine + ATP
Fumarate Glutamate + AMP
Adenylic acid Guanylic acid
GMP AMP
nucleotidases IMPderulate deaminase
Guanosi ne Inosine4 N Adenosi ne
adenosine deaminase
nucleoside
phosphory lases
Guani ne
HN Hupoxanthi ne
NH, xanthine ox1dase
"H02
Yanthine odace
H H -0
Xenthine Hz02 Urate
De novo pathway pyrimidine biosynthesis
P
CPS ATCase
HCO, + Glutamine +2 ATP + H,0
s CH,
-N-H
Ghatam
2 ADP P Carbamoyt
sCH, Carbamoyl-Asp
H,NC-H
H
UMP
Aspartate
Dibydroorotase OH
Co,
OMP decarboxylase
H.
0 Orotate phospho H H
ribosyltransferase DHO dehydrogenase
P-CH, =0
PP -PRPP Coenzyme Coenzyme C=0
H QH, H 0
OH OH Orotate (a pyrimidine) Dilydroorotate (DHO)
Orotidine-$'-Monophouplhate (OMP)
Salvage pathway of pyrimidine biosynthesis
Purine Biosynthesis
NN
-0-H, -0-CH, P-0-CH, H Mathony
-0-H,c Hfot
Mgi
--0 ATP ADP.P H MFormyitraraforaseo NH
PRPP
Synithase RsP)
-ibe pha SPhospho bosylamine
pyrophosphate (PRPP) iboeykSohasphate Formylglyoinamide
ribosy
COO ABP ATP, Mg
HO Ring cloure
CH
HC
IK Syease WCatorjae H,N H
Furmarate R-5-(P)
hoeohos phate carborylate ribosytsphosphate ribosy-5-phosphate
v
H.ae
H,N
Foyitrnster Arngcosre
HN
AMP Cyoohyauase
Aminoimidazole carboxamide Fornimidoimidarole carboamide eoaioe mgnoghosphate (MP)
ribosy-6phosphate ribosyl
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age pathway of purine biosynthesis