BCH 3120 Lecture Notes - Lecture 19: Purine Metabolism, Purine, Tryptophan
28 Apr 2018
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March 15, 2017
Nucleotide Metabolism: Purine Biosynthesis
Nucleotides
Not a significant source of energy
All cells can make nucleotides
Metabolism is highly conserved
-Originally studied in pigeons
Purine Biosynthesis
Purine:
- "
-Glycine is only multiple atom building block in purine biosynthesis, all other heavy atoms added one at a time
IMP is source of purines: source of AMP and GMP
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1
March 15, 2017
IMP Biosynthesis: Step 1
R5P from pentose phosphate pathway
-Also the fist step in tryptophan and histidine biosynthesis
Needs ATP
Allosterically regulated: inhibited by ADP and GDP
IMP Biosynthesis: Step 2
First unique reaction in purine biosynthesis
Needs glutamine: takes N side chain from Gln
-NH3 will be channeled to PRPP and displaces PPi
Exergonic reaction: PPi will be hydrolyzed
Amidophosphoribosyl transferase: 2 domain protein
-1 hydrolyzes Gln to make NH3
-1 is a regulatory domain
-Key regulation point in IMP biosynthesis
Allosteric regulation:
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March 15, 2017
-Inhibition: regulatory domain has 2 binding sites - A based and G based inhibitors can bind together, highly
inhibiting when bound together
•Inhibited by ATP, ADP, and AMP
•Also inhibited by GTP, GDP, GMP
-Activated by PRPP
PRA: very unstable
IMP Biosynthesis: Step 3
PRA is shuttled directly to GAR synthetase
Needs glycine and ATP
Creates an amide bond with glycine, now very stable
Reversible step
IMP Biosynthesis: Step 4
Formylation of alpha amine
GAR transformylase brings substrate into close proximity
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Document Summary
Glycine is only multiple atom building block in purine biosynthesis, all other heavy atoms added one at a time. Imp is source of purines: source of amp and gmp. Also the st step in tryptophan and histidine biosynthesis. Needs glutamine: takes n side chain from gln. Nh3 will be channeled to prpp and displaces ppi. Inhibition: regulatory domain has 2 binding sites - a based and g based inhibitors can bind together, highly. March 15, 2017 inhibiting when bound together: inhibited by atp, adp, and amp, also inhibited by gtp, gdp, gmp. Creates an amide bond with glycine, now very stable. 1 c transfer - seen in gly cleavage system and met formation. Requires glutamine: nh3 will be taken from glutamine. 1 activates amide bond by phosphorylation and then adds nh3. Needs atp: reaction is driven by atp hydrolysis. In humans, air synthetase, gar synthetase, and gar transformylase are all in a single polypeptide - trifunctional purine biosynthesis protein adenosine-3.
