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Lecture notes of 8 pages for the course Metabolic Pathways at QMUL
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Purines & pyrimidines IILearning objectives:
1. Understand the regulation features required in the biosynthesis of purines
2. Pyrimidine rings are biosynthesised first then converted to the sugar ring
3. Understand the steps in the process of pyrimidine biosynthesis
4. Note the salvage pathway for pyrimidines
5. Identify the similarities and differences (compare and contrast) biosynthesis and regulation of the salvage pathway
between purines and pyrimidines
LO1. UNDERSTAND THE REGULATION FEATURES REQUIRED IN THE BIOSYNTHESIS OF PURINES
Purines biosynthesis regulation
A tight control
Critical balance needed
ATP to GTP
IMP pathway
Regulated at first 2 priming step reactions
Inhibition
First reaction (primer 1) produced PRPP production, which is an important product
- Feedback inhibition occurs for this step by IMP, AMP, GMP
Second reaction (primer 2) produces 5-phosphoribosyl-1-amine production
- This is the flux-generating step
- Feedback inhibition occurs here as well
By AMP, ADP, ATP at 1 site in the enzyme
By GMP, GDP, GTP & XMP at another sit of the enzyme
IMP competitive inhibition by AMP & GMP
- If concentration of AMP is high
- AMP production is inhibited
- Same for GTP
Activation
Feedforward activation by PRPP to create β-5-phosphoribosylamine
Powering steps are steps 1a & 2b
- GTP required to form AMP
- ATP required to form GMP
, Salvage pathways of purines
Cells degrade nucleic acids
- often RNA
Free purines produced
Salvaged for reuse
Vital processes
- Processes differ in different species
- Mammals have 2 principle enzymes
1. Adenine phosphoribosyltransferase
Adenine + PRPP => AMP + PPi
2. Hypoxanthine phosphoribosyltransferase (HPRT or HGPRT)
hypoxanthine + PRPP => IMP + PPi
guanine + PRPP => GMP + PPi
Deficiency in HGPRT
- lesch-nyhan syndrome
Pyrimidines
LO3. UNDERSTAND THE STEPS IN THE PROCESS OF PYRIMIDINE BIOSYNTHESIS
Biosynthesis of pyrimidines
2 methods
- De novo
Forms: uridine monophosphate
- Salvage pathway
De novo biosynthesis of pyrimidines
6 step process
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