BCH 3120 Lecture Notes - Lecture 20: Phosphoribosyl Pyrophosphate, Urea Cycle, Thymidine Triphosphate

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March 20, 2017
Nucleotide Metabolism - Pyramidine Biosynthesis
Pyramidines
Biosynthesis is much sympler
-UMP is made
-CTP is made from UMP
-UMP makes dUDP, which generates dTTP
UMP Biosynthesis: Step 1
Similar to urea cycle, but uses Gln instead of Gly as the N source
Occurs in the cytosol
Allosteric control:
-Inhibited by UDP and UTP
-Activated by ATP and PRPP (downstream substrate)
1
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March 20, 2017
UMP Biosynthesis: Step 2
Adds to the alpha-amino group of Asp
Main regulatory control point in bacteria, but not in mammals
UMP Biosynthesis: Step 3
Intramolecular ring closure - no energy requirement
Urea O attacks the carboxylic acid
NB: first three enzymes are one one polypeptide (steps 1-3)
-Enables substrate channeling - keeps intermediates associated to enzymes
2
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Document Summary

Similar to urea cycle, but uses gln instead of gly as the n source. Activated by atp and prpp (downstream substrate) Main regulatory control point in bacteria, but not in mammals. Nb: rst three enzymes are one one polypeptide (steps 1-3) Enables substrate channeling - keeps intermediates associated to enzymes. On the outer surface of the inner mitochondrial membrane. Coq supplies the oxidizing power - goes to complex iii. Oxidation of the carbons to give sp2 hybridization in order to aromatize the system. Prpp comes from step 1 of purine biosynthesis (r5p and atp) Can also use uracil and cytosine - pyrimidine salvage pathway. Nb: purines also have a salvage pathways: adenine + prpp > amp. Regulated step - irreversible since co2 is lost. Nucleoside monophosphate kinase: ump + atp = udp + adp. Nucleoside disphosphate kinase: udp + atp = utp + adp. Uses gun as an ammonia source, like fgam synthetase and gmp synthestase.

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