Nucleotide metabolism

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Nucleotide metabolism
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Nucleotide Metabolism

• Nucleotides
• -Why have them?
• -Nomenclature
• II. Purine Biosynthesis
• III. Pyrimidine Biosynthesis
• IV. Nucleotide Catabolism

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NucleotidesWhy have them?

• I. Nucleotide triphosphates (NTPs) and
  deoxynucleotide triphosphates
• (dNTPs) are activated precursors of RNA and
  DNA synthesis
• II. ATP, the universal currency of energy.
• III. NTPs required in the activation of
  molecules in synthetic pathways.
• IV. NTPs regulate protein function.
• -through phosphorylation
• -through binding and hydrolysis (G-proteins,
  Chaperones)
• V. Signal Transduction
• -formation of cyclic nucleotides
• VI. Synthesis of nicotinamide (NAD), flavin
  (FAD) and co-enzyme A.

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Nomenclature Purines vs Pyrimidines
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Nomenclature
Nucleoside Nucleotide
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Structure of nucleotides
pyrimidine
purine
OR
N-b-glycosyl bond
Ribose or 2-deoxyribose
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Purine Biosynthesis
Isotopic labeling experiments defined the
precursors.
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Purine Biosynthesisin the beginning there was
PRPP
The use of ribose links the pentose phosphate
pathway to nucleotide metabolism.
The purine ring is built upon ribose using PRPP
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Purine Biosynthesisthe first committed step
It is always a good idea to know the first
committed step of any pathway.
Glutamine-PRPP amidotransferase
1
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Purine Biosynthesisaddition of glycine
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Purine Biosynthesisformylation 1
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Purine Biosynthesisamidotransferase 2
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Purine Biosynthesisimidazole ring closure
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Purine Biosynthesiscarboxylate me, baby
Carbon is the wrong position based on isotope
labeling exp.
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Purine Biosynthesismove the carbon
Now the carbon is placed correctly.
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Purine Biosynthesis aspartate addition
But all we need is the nitrogen.
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Purine Biosynthesisfumarate subtraction
One more carbon.
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Purine Biosynthesisformylation 2
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Purine Biosynthesisfinally a purine
But who needs inosinate?
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Conversion of IMP to AMP and GMP
Note GTP is used for AMP synthesis.
Note ATP is used for GMP synthesis.
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Formation of AMP and GMP(What you really to know
about the previous slide.)
IMP is the precursor for both AMP and GMP.
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Salvage Pathways Specific Enzymes
Adenosine phosphoribosyltransferase
Hypoxanthine-guanine phosphotransferase (HGPRT)
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Biosynthesis of pyrimidines
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(No Transcript)
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Purine Catabolismuric acid

• 1. Remove phosphate.
• -5-nucleotidase
• 1a. Deaminate adenosine
• -Adenosine deaminase
• 2. Remove the ribose.
• -nucleosidase
• 3. Generate xanthine.
• -oxidize hypoxanthine
• -deaminate guanine
• Make uric acid.
• -xanthine oxidase