Nucleotide Biosynthesis nucleotides is essential for life processes

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

Purines and Pyrimidines Adenine Two Purines Guanine Two Pyrimidines Thymine/Uracil Cytosine

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) de novo Pathway Salvage 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 • Synthesized from: – – Glutamine CO 2 Aspartic acid Requires ATP Uracil Cytosine � Pyrimidine rings are synthesized independent of the ribose and transferred to the PRPP (ribose) � Generated as UMP (uridine 5’-monophosphate)

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. CTP is Formed by Amination of UTP

DENOVO Synthesis of Pyrimidine

Purine Biosynthesis (de novo) � Atoms derived from: Aspartic acid Glycine Glutamine CO 2 Tetrahydrofolate � Also requires Inhibited by AMP, GMP, IMP X 4 ATP’s Committed Step Purines are synthesized on the Ribose ring

DENOVO Synthesis of Purine

Salvage Pathway for Purines Hypoxanthine or Guanine Adenine + PRPP = IMP or GMP + PPi Hypoxanthineguanosylphosphoribosyl transferase (HGPRTase) + 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 which your kindly professor does not expect you to know in detail

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