Nucleotide Biosynthesis

1
Nucleotide Biosynthesis

• PRPP synthesis
• Purines
• Carbamoyl phosphate synthetase II
• Pyrimidines
• Nucleoside kinases
• Deoxyribonucleotides

2
Biosynthesis of Purine Nucleotides
5-UMP
5-AMP
Pyrimidine
Purine
3
Purine Synthesis
10 Steps
1. Activate the Ribose (PRPP)
10. Close large ring
5. Close small ring
4
ATP
AMP
PRPP Synthetase
Ribose-5-P
5-Phosphoribosyl-PP
(PRPP)
Activate Ribose
PRPP allows ribose to be joined to a base
5
5-phosphoribosylamine
L-glutamine
5-PRPP
Glycine
6
Formyl-THF
Glutamine
Ring Closure
7
CO2
ATP
L-aspartate ATP
8
Formyl-THF
R OPO3CH2
Ring closure
R
Inosine 5-phosphate
9
Summary of Purine Biosynthesis
Amino acids
Glutamine 2
Glycine 1
Aspartate 1
Coenzymes
1 PRPP synthesis
N10-formyl THF 2
1 Glutamine
Energy
1 Glycine
ATP 6
1 Aspartate
Others
1 CO2
CO2 1
1 Small ring closure
Ribose-5-PO4 1
10
Asp GTP
5AMP
NAD
Adenylsuccinate
Glutamine
5-XMP
ATP
5-GMP
11
5-AMP
ADP
ATP
5-IMP
dADP
dATP
5-XMP
5-GMP
GDP
GTP
Summary of Purine Nucleotide Biosynthesis
dGDP
dGTP