Nucleotide Synthesis Flashcards
General sequence of nucleotide synthesis (3 steps)
nucleic acid + sugar —> nucleoside + phosphate —> nucleotide
Nucleotides VS nucleosides VS nucleic acids
Nucleoside = sugar + base (guanine, uracil, cytosine, adenine, thymine)
Nucleotides = sugar + base + phosphate
Nucleic acids = nucleotide + nucleotide
Purines
a base made from 5 carbons, 4 nitrogens, and is a polycyclic ring
produced via the salvage pathway (i.e. attached to a ribose)
Pyrimidines
a base made from mono-cyclic, 4 carbons and 2 nitrogens
produced through the de novo pathway, i.e independently
phosphoribosyl pyrophosphate
PRPP, central constituent of nucleotide metabolism
synthesized from ribose phosphate and ATP
Where does the ribose in purines come from?
contributed by PRPP
the committed step in purine step is
the synthesis is phosphoribosyl amine
What amino acids are added to phosphoribosyl amine?
PRPP + glutamine –> PR-amine + glutamic
PR-amine + glycine + 1 carbon (thf) + a nitrogen (glutamine) + ring closure = 5 member ring
Inosine monophosphate
(IMP): the product of PRPP after several atoms from amino acids and carbon dioxide are added to the first ring,
and the second ring is closed
IMP is converted to
AMP or GMP
phosphoribosyl amine —>
hypoxanthine ribose or inosine monophosphate
the Salvage Enzymes
hypoxanthine guanine phosphoribosyl transferase
adenine phosphoribosyl transferase
Regulation of purine nucleotide synthesis
synthesis of PRPP and PR-amine - feedback inhibited
synthesis of AMP/GMP from IMP - feedback inhibited
AMP synthesis (+) stimulated by GTP; ATP synthesis (-) inhibited by AMP
GMP synthesis (+) stimulated by ATP; GMP synthesis (-) by GMP
Ribose-5-phosphate–> PRPP—>Phosphoribosyl-amine
how is this pathway leg regulated?
PRPP synthesis is regulated by high IMP, AMP, and GMP
PR-amine synthesis is regulated by high IMP, AMP, and GMP
IMP—> adenylo succinate— > AMP
how is this regulated? where?
inhibited by AMP
IMP–>AS
IMP–> xanthylate –> GMP
how is this regulated? where?
inhibited by GMP
IMP–XAN
Purine Ring Synthesis (big strokes), DNA and RNA synthesis
1) Base + sugar –> Ribose 5 phosphate
2) ATP + ribose 5 phosphate –> PRPP
3) PRPP + Glutamine —> PR-amine
4) PR-amine + glycine –> 5 membered ring
5) 5 membered + aspartate –> inosine monophosphate (IMP)
6) IMP —> ATP –> RNA
IMP —> ATP –> dATP –> DNA
7) IMP —> GTP –> RNA
IMP —> dGTP –> DNA
8) IMP –> AMP (adenylate)
9) IMP –> GMP (guanylate)
Pyrimidine synthesis
What enzyme catalyzes the first step in this pathway?
Bicarbonate + NH3 + 2 ATP —> ring + aspartate –> pyrimidine ring + PRPP –> UTP
UTP —> CTP –> RNA
UTP —> TTP –> DNA
UTP –> CTP –> dCTP –> DNA
ATCase (aspartate transcarbamoylase)
The committed step in pyrimidine synthesis is…?
The transfer of aspartate to carbomyl phosphate via ATCase
UMP + ATP rxn
Demonstrates the reversible interconversation of phosphate groups on nucelosides, catalyzed by “nucleoside monophosphate kinases” and the diphosphate kinases
regulation of pyrimidine synthesis (2)
carbomyl phosphate synthesis is inhibited by UMP and purines, and stimulated by PRPP
Inhibition by UMP:
CO2+glutatmine+ATP — / –> carbomyl phosphate
Inhibition of ATCase via UTP
Aspartate transcarbamoylase — / –>
Carbamoyl phosphate + aspartate —>
N-carbamoylasparate (the pyrimidine ring)
catalyzed by ATCase (aspartate transcarbamoylase)
Orotic acid –> Orotidylate
what? how is it regulated?
Orotic acid = main intermediate in uracil formation
Orotic acid –> —> UMP
Catalyzed by PRPP
deoxyridbonucleoside formation
ribonucleoside diphosphate —reduction–> deoxyribonucleoside diphosphate
Enzymes B1 and B2 involved
ADP/GDP/CDP/UDP—via ribonucleotide reductase–> dADP/dGDP/dCDP/dUDP–> dATP/dGTP/dCTP/dTTP
ribonucleoside diphosphate —>
deoxyribonucleoside diphosphate (ATP/GDP/CDP/UDP) — Ribonucleotide reductasse —> d version of each –> DNA
DNA synthesis: the limiting factor
is dTTP from ribose diphosphate reduction
What is the ultimate end of product of purine catabolism?
uric acid, which we excrete as uric acid in the urine
