purine nucleotides Flashcards
purine biosynthesis
made from glutamine, glycine, 10-formyl-THF, and aspartate
only need to know certain steps:
first committed step of pathway is PRPP amidotransferase - highly regulated
two steps depend on N10-formyl-THF-transferases so folic acid deficiency inhibits de novo purine biosythesis
IMP is end product
PRPP amidotransferase AKA glutamine phosphoribosyl pyrophosphate amidotransferase
enzyme responsible for first step of de novo purine biosynthetic pathway
inhibited by AMP, GMP, IMP
activated by PRPP
converts 5’-phosphoribosyl-1-pyrophosphate (PRPP) to 5’phosphoribosylamine
first committed step in pathway
highly regulated
PRPP synthetase
activated by Pi and inhibited by IMP, AMP and GMP (purine nucleotides)
allows for synthesis of purines to be linked to energy level of cell
converts ribose 5-phosphate to 5-phosphoribosyl-1-pyrophosphate (PRPP)
AMP/GMP synthesis
conversion of IMP (end-product of de novo purine synthesis pathway) to AMP or GMP is subject to negative feedback regulation
GMP inhibits IMP dehydrogenase, which is the first enzyme in the conversion of IMP to GMP
AMP inhibits adenylosuccinate synthetase, which is the first enzyme in the conversion of IMP to AMP
where the IMP could go either way (to GMP or AMP) is the branch point
IMP dehydrogenase
converts IMP to xanthosine monophosphate, which is then converted to GMP
inhibited by GMP
adenylosuccinate synthetase
converts IMP to adenylosuccinate, which is used to make AMP
inhibited by AMP
AMP synthesis
1: IMP is converted to adenylosuccinate by adenylosuccinate synthetase - uses aspartic acid and GTP - releases GDP and Pi
2: adenylosucinase converts adenylosuccinate into fumarate and AMP
AMP then inhibits adenylosuccinate synthetase
salvage pathways
free purine bases that result from normal turnover of cellular nucleic acids or that are obtained from diet are salvaged via conversion to nucleoside triphospahtes
enzymes involved are hypoxanthine-guanine phosphoribosyl transferase (HGPRT) and adenine phosphoribosyl transferase (APRT)
both use PRPP
release pyrophosphate so irreversable
hypoxanthine-guanine phosphoribosyl transferase (HGPRT)
enzyme involved in salvage of free purine bases
converts hypoxanthine to IMP
converts guanine to GMP
uses PRPP and releases PPi
because of generation of PPi, is irreversible
deficiency results in Lesch-Nyhan syndrome
adenine phosphoribosyltransferase (APRT)
enzyme involved in salvage of free purine bases
converts adenine to AMP
uses PRPP
releases PPi, and therefore is irreversable
purine degradation
excess purines degraded to uric acid, which is excreted in urine
1a: hypoxanthine converted to xanthine by xanthine oxidase - uses O2 and H2O and makes H2O2
1b: guanine converted to xanthine by aminohydrolase - uses H2O and releases NH3
2: xanthine converted to uric acid by xanthine oxidase - also uses H2O and O2 and makes H2O2
nucleosides
called this when the pyridine base is attached to ribose
nucleotides
called this when the pyridine base is attached to phosphate group
inosine nucleotide
when hypoxanthine group attached to pyridine base
lesch-nyhan syndrome
x-linked recessive - 1/100,000 frequency
caused by mutations in HGPRT
severity correlates with level of HGPRT activity
mental retardation, spasticity, compulsive self injury - no molecular explanation for neurological side effects yet
hyperuricemia - over-productive gout and associated problems
treat with physical restraints to prevent self injury - allopurinol to control gout
