Title: Nucleotide metabolism
1Nucleotide metabolism
2Nucleotide Metabolism
- Nucleotides
- -Why have them?
- -Nomenclature
- II. Purine Biosynthesis
- III. Pyrimidine Biosynthesis
- IV. Nucleotide Catabolism
3NucleotidesWhy 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.
4Nomenclature Purines vs Pyrimidines
5Nomenclature
Nucleoside Nucleotide
6Structure of nucleotides
pyrimidine
purine
OR
N-b-glycosyl bond
Ribose or 2-deoxyribose
7Purine Biosynthesis
Isotopic labeling experiments defined the
precursors.
8Purine 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
9Purine Biosynthesisthe first committed step
It is always a good idea to know the first
committed step of any pathway.
Glutamine-PRPP amidotransferase
1
10Purine Biosynthesisaddition of glycine
11Purine Biosynthesisformylation 1
12Purine Biosynthesisamidotransferase 2
13Purine Biosynthesisimidazole ring closure
14Purine Biosynthesiscarboxylate me, baby
Carbon is the wrong position based on isotope
labeling exp.
15Purine Biosynthesismove the carbon
Now the carbon is placed correctly.
16Purine Biosynthesis aspartate addition
But all we need is the nitrogen.
17Purine Biosynthesisfumarate subtraction
One more carbon.
18Purine Biosynthesisformylation 2
19Purine Biosynthesisfinally a purine
But who needs inosinate?
20Conversion of IMP to AMP and GMP
Note GTP is used for AMP synthesis.
Note ATP is used for GMP synthesis.
21Formation of AMP and GMP(What you really to know
about the previous slide.)
IMP is the precursor for both AMP and GMP.
22Salvage Pathways Specific Enzymes
Adenosine phosphoribosyltransferase
Hypoxanthine-guanine phosphotransferase (HGPRT)
23Biosynthesis of pyrimidines
24(No Transcript)
25Purine 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