Lecture 11 Flashcards
Nucleotides are more than precursors for RNA and DNA
Energy, substrates, phosphorylation, signaling, enzyme cofactors
ATP, GTP, SAM, NADH, GDP, FAD, UDP-Glucose, cAMP
Nucleotide Metabolism
Ribose carbons numbered with a prime
Distinguish sugar from the purine or pyrimidine base
The sugar, not the purine or pyrimidine bases, distinguishes RNA from DNA
Purines
Adenine and guanine
Pyrimidines
cytosine
thymine (DNA)
uracil (RNA)
Major and minor forms of purines and pyrimidines - tautomerization
Tautomerization can lead to unusual base pairing interactions and can (rarely) cause mutations
People used to think minor forms were major ones
Differ in location of double bond or proton
Nucleotide Metabolism - nomenclature
Difference between nucleosides and nucleotides is the 5’ phosphate (Phosphate is attached to the ribose group)
Nucleosides: adenosine and deoxy-adenosine
Nucleotides: Adenylate or deoxy-adenylate
The 2’ OH makes RHA less stable than DNA, gives certain RNAs catalytic properties (ribozymes)
How can nucleotides arise?
De novo synthesis or salvage pathways
What is difference between purine and pyrimidine de novo synthesis?
In Purine synthesis, start with PRPP and then add atoms. In pyrimidine, start with atoms and then add PRPP.
What is the committed step in Purine synthesis?
Production of 5’ phospho beta ribosylamine
Makes PrPP using atp and PRPP synthase
PRPP is an important int drives PRA synthesis reaction forward.
Purines are built up stepwise on a ribose platform
Which metabolic enzymes involved in nucleotide metabolism form filaments?
CTPS (e coli), human enzyme forms filaments with high activity IMP dehydrogenase ( IMPDH) filaments in different conformations. Morphs between active state (smushed) and inactive state (stretched). GTP turns off own synthesis, turns off smushed/active state.
How many different enzymes needed to convert into deoxy counter parts?
Just one for all four, keeps them in balance
Synthesis of deoxy-nucleotides
Most of the carbon flux in nucleotide metabolism generates ribonucleotide triphosphate (rNTPs)
rNTPs have multiple metabolic roles
most cells have 5-10x as much RNA as DNA
Only a small percentage of rNTPs goes toward the synthesis of deoxy-nucleotides (dNTPs)
dNTPs have only one purpose- DNA synthesis and repair
critical to cell viability
Must keep all four dNTPs in balance! If they are out of balance, could be mutagenic
One enzyme for conversion of all four
What are the major differences between rNTPs and dNTPs?
The pyrimidine thymine is only found and a dNTP
The pyrimidine uracil is only found as an rNTP
(dUPT is very rapidly converted to dTTP)
The 2’ hydroxyl group
