Nucleotide Metabolism Flashcards
What are the two types of heterolytic rings?
Purines and pyrimidine
What are nucleotides?
The phosphate esters of nucleosides
Nitrogenous base + sugar + phosphate
What are nucleosides composed of?
Nitrogenous base + sugar
True or false: dATP is equivalent to ATP
False
What is different about a deoxynucleotide?
There is no OH group on C2
Hypoxanthine and xanthine are classified as purine or pyrimidines?
Purines
What are the two ways in which purines can be synthesized?
De novo synthesis and salvage pathway
Briefly describe de novo purine synthesis and its location
Site: liver, cytosol
Formation of purine base on ribose-5-phosphate from the PPP
Briefly describe the purine salvage pathway and its location
Site: organelles
Addition of ribose 5P to the preformed purine base
What are the two ways in which pyrimidine nucleotide synthesis can occur?
De novo synthesis and the salvage pathway
Briefly describe de novo pyrimidine synthesis and its location
Site: liver, cytosol, mitochondria
Formation of pyrimidine ring structure followed by the addition of ribose phosphate
Briefly describe the pyrimidine salvage pathway and its location
Site: organelles
Formation of pyrimidine nucleotides from pyrimidine bases in RNA/DNA
What are the phases of purine synthesis?
- Activation of ribose 5 phosphate
- Conversion of PRPP into phosphoribosylamine
- Construction of inosine monophosphate (branch point)
- Conversion of IMP into adenosine and guanosine
Describe phase I: activation of ribose 5 phosphate in purine synthesis
Starts with ribose 5 P which is a byproduct of the oxidative phase of the PPP
Converted to active form, 5-phosphate alpha D ribosyl - 1-pyrophosphate (PRPP)
Utilizes ATP and requires PRPP synthetase
Explain the specific roles of nucleosides and nucleotides
Nucleotides such as ATP and GTP are important cosubstrates in an array of enzymatic reactions
Nucleotides are also components of several cofactors, including CoA, FAD, FMN, UDP-Gln and NADPH and NADH
Nucleotides such as cAMP and cGMP play regulatory roles and serve as stabilizing energy elements
Nucleosides also appear in important biomolecules such as adenosine in vitamin B12
What is PRPP synthetase (phase I purine synthesis) regulated by?
Allosterically activated by phosphate levels (Pi levels signal cellular activity due to ATP consumption)
Negatively regulated by levels of purine nucleotides GMP, AMP and IMP
Describe phase II: conversion of PRPP into phosphoribosylamine in purine synthesis
Glutamine:phosphoribosyl pyrophospphate aminotransferase substitutes pyrophosphate with an amino group at C1 or PRPP
Obtains the amino group from glutamine
Generates phosphoribosylamine (PRA)
What is phase II of purine synthesis regulated by?
Allosterically positively regulated by PRPP levels
Negatively regulated by the levels of purine nucleotides GMP, AMP and IMP
Describe phase III: construction of inosine monophosphate in purine synthesis
PRA enters 9 step ring constructing sequence that produces IMP All intermediates are phosphorylated (nucleotides) due to the phosphate group on R5P Consumes ATP(4) in reaching IMP IMP is the branch point in anabolism of purines
Where do the C and N come from in purine synthesis?
2 C’s from folate derivative, 1 C from CO2, remaining C’s and N’s from amino acids Gln, Gly and Asp