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

CHNC

CNC

NCNH2

H

NCC

CHN

C

OCH3

HO

HN

CC

CNC

HO

H

HNH2

HN

CHNC

CNC

NCO

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

NCC

CHN

C

OCH3

HO

HN

CC

CNC

HO

H

HNH2

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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