Purine and Pyrimidine Flashcards
Initial nucleotide product in purine synthesis?
IMP
Initial nucleotide product in pyrimidine synthesis
UMP
In what form is I converted to G and A?
As a monophosphate
IMP –> AMP and GMP
In what form in U converted to C?
As a triphosphate
UTP –> CTP
CTP synthetase
PRPP?
Activated form of ribose-5-phosphate
First step in synthesis of purines is to activate the ribose sugar –> PRPP
PRPP Synthase
Enzyme that forms PRPP
Allosterically activated by Pi
Allosterically inhibited by Purine ribonucleotides (AMP, GMP, IMP, etc)
Where does Purine synthesis start and where does it end?
Starts at PRPP (build on activated sugar)
Ends at IMP
MOST important regulated step in purine synthesis?
First step
Glutamine phosphoribosyl pyrophosphate amidotransferase
==> enzymatic addition of nitrogen to from glutamine to PRPP
Activators of glutamine phosphoribosyl pyrophosphate amidotransferase?
Inhibitors?
PRPP
AMP, GMP, IMP
Sources of atoms for purine synthesis?
Glutamine Glycine Aspartate also requires... ATP THF - methotrexate target! CO2
So once we have IMP we need to make AMP and GMP
GTP fuels AMP production
ATP fuels GMP production
AMP inhibits AMP produciton
GMP inhibits GMP production
Pyrimidine synthesis starts at?
Ends at?
CO2 (ATP) and Glutamine
UMP
Key regulatory step in pyrimidine synthesis?
First step (build base alone) Carbamoyl phosphate synthetase II
Inhibited by UTP
Activated by ATP
What makes CPSI and CPSII different?
Location - cytosol vs mito
Source of N - ammonia vs glutamine
Regulation - N-acetylglutamate vs. ATP (UTP)
Enzyme that converts ribonucleotides to deoxy?
ribonucleotide reductase
Potent inhibitor of ribonucleotide reductase (and thus inhibitor of dNTP synthesis?)
dATP
How do we make dTMP?
From dUMP
via
Thymidylate synthase
Who helps us with conversion of dUMP to dTMP?
THF (T is just U with a methyl)
- Target of methotrexate
5-fluorouracil also targets this conversion via fucking with some intermediary
Purine degradation
starts with
AMP or GMP
Purine degradation ends with
uric acid
Adenosine deaminase deficiency leads to
SCID
because we have buildup of dATP which inhibits ribonucleotide reductase
Gout
Build-up of uric acid - primarily from undersecretion but could also be due to overproduction and subsequent degradation of purines- treat by blocking xanthine oxidase
xanthine oxidase
converts xanthine to uric acid - target of gout treatment
Lesch Nyhan
X linked recessive
deficiency of HGPRT so can’t convert hypoxanthine to IMP or guanine to GMP
Fucked up purine salvage pathways :( –> increased levels of PRPP and decreased IMP and GMP causing increased de novo purine synthesis
excessive production and accumulation of uric acid –> nuerologic