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Nucleotide metabolism

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It is always a good idea to know the first committed step of any pathway. ... Carbon is the wrong position based on isotope labeling exp. Purine ... – PowerPoint PPT presentation

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Title: Nucleotide metabolism


1
Nucleotide metabolism
2
Nucleotide Metabolism
  • Nucleotides
  • -Why have them?
  • -Nomenclature
  • II. Purine Biosynthesis
  • III. Pyrimidine Biosynthesis
  • IV. Nucleotide Catabolism

3
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.

4
Nomenclature Purines vs Pyrimidines
5
Nomenclature
Nucleoside Nucleotide
6
Structure of nucleotides
pyrimidine
purine
OR
N-b-glycosyl bond
Ribose or 2-deoxyribose
7
Purine Biosynthesis
Isotopic labeling experiments defined the
precursors.
8
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
9
Purine Biosynthesisthe first committed step
It is always a good idea to know the first
committed step of any pathway.
Glutamine-PRPP amidotransferase
1
10
Purine Biosynthesisaddition of glycine
11
Purine Biosynthesisformylation 1
12
Purine Biosynthesisamidotransferase 2
13
Purine Biosynthesisimidazole ring closure
14
Purine Biosynthesiscarboxylate me, baby
Carbon is the wrong position based on isotope
labeling exp.
15
Purine Biosynthesismove the carbon
Now the carbon is placed correctly.
16
Purine Biosynthesis aspartate addition
But all we need is the nitrogen.
17
Purine Biosynthesisfumarate subtraction
One more carbon.
18
Purine Biosynthesisformylation 2
19
Purine Biosynthesisfinally a purine
But who needs inosinate?
20
Conversion of IMP to AMP and GMP
Note GTP is used for AMP synthesis.
Note ATP is used for GMP synthesis.
21
Formation of AMP and GMP(What you really to know
about the previous slide.)
IMP is the precursor for both AMP and GMP.
22
Salvage Pathways Specific Enzymes
Adenosine phosphoribosyltransferase
Hypoxanthine-guanine phosphotransferase (HGPRT)
23
Biosynthesis of pyrimidines
24
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25
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
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