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Nucleotide Biosynthesis
nucleotides is essential for life processes
nucleotides are the activated precursors of nucleic acids. As such, they are necessary for the replication of the genome
an adenine nucleotide, ATP, is the universal currency of energy. A guanine nucleotide, GTP, also serves as an energy source for a more select group of biological processes.
Third, nucleotide derivatives such as UDP-glucose participate in biosynthetic processes such as the formation of glycogen.
nucleotides are essential components of signal-transduction pathways. cyclic AMP and cyclic GMP are second messengers that transmit signals both within and between cells.
RNA & DNA
RNA & DNA
Purines and Pyrimidines
Adenine Guanine
Thymine/Uracil Cytosine
TwoPurines
TwoPyrimidines
HN
CHN
C
CN
CN
C
NH2
H
NC
CC
HN
C
O
CH3
HO
HN
C
CC
N
CH
O
H
H
NH2
HN
CHN
C
CN
CN
C
O
H2N
H
Synthesis Pathways
For both purines and pyrimidines there are two means of synthesis (often regulate one another) de novo (from bits and parts) salvage (recycle from pre-existing nucleotides)
Salvage Pathwayde novo Pathway
Many Steps Require an Activated Ribose Sugar (PRPP)
5’
de novo Synthesis
Committed step: This is the point of no return Occurs early in the biosynthetic pathway Often regulated by final product (feedback inhibition)
X
Biosynthesis of Pyrimidines
Pyrimidine rings are synthesized independent of the ribose and transferred to the PRPP (ribose)
Generated as UMP (uridine 5’-monophosphate)
• Synthesized from:– Glutamine– CO2
– Aspartic acid– Requires ATP
NC
CC
HN
C
O
CH3
HO
H
NC
CC
N
CH
O
H
H
NH2
Uracil Cytosine
DENOVO Synthesis of Pyrimidine
DENOVO Synthesis of Pyrimidine
1 . Bicarbonate and Other Oxygenated Carbon Compounds Are Activated by Phosphorylation
2 . Orotate Acquires a Ribose Ring from PRPP to Form a Pyrimidine Nucleotideand Is Converted into Uridylate
DENOVO Synthesis of Pyrimidine
3 . C T P i s Fo r m e d b y A m i n a t i o n o f U T P
DENOVO Synthesis of Pyrimidine
Purine Biosynthesis (de novo)
Atoms derived from: Aspartic acid Glycine Glutamine CO2
Tetrahydrofolate Also requires
4 ATP’s
Purines are synthesized on the Ribose ring
Committed Step
Inhibited byAMP, GMP, IMP X
DENOVO Synthesis of Purine
DENOVO Synthesis of Purine
DENOVO Synthesis of Purine
Salvage Pathway for Purines
Hypoxanthineor
Guanine
+ PRPP = IMP or GMP + PPi Hypoxanthineguanosylphosphoribosyl transferase
(HGPRTase)
Adenine + PRPP = AMP + PPi Adeninephosphoribosyl transferase
(APRTase)
Biosynthesis: Purine vs Pyrimidine
Synthesized on PRPP
Regulated by GTP/ATP
Generates IMP Requires Energy
Synthesized then added to PRPP
Regulated by UTP Generates UMP/CMP Requires Energy
Both are very complicated multi-step process whichyour kindly professor does not expect you to know in detail
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