nucleotide metabolism (20) Flashcards
what are the 4 purines?
adeninin
guanine
hypoxanthine
xanthine
what are the 3 pyrimidines?
uracil
thymine
cytosine
list the 2 sources of ribose 5 phosphate
- glucose metabolism, pentose phosphate shunt
- nucleoside degradation generates ribose-1-phosphate (which can be converted to R5P)
what two compounds are needed to synthesize PRPP? what is the enzyme?
ATP and ribose 5 phosphate
enzyme: PRPP synthase
list the 3 things that PRPP is required for
- De novo synthesis of pyrimidine & purine nucleotides
- The salvage pathways for purine nucleotides
- The biosynthesis of nucleotide coenzymes NAD and FAD
is this statement describing purines or pyramide synthesis?
the ring is built on a molecule of PPRP
purines
list the precursors for the purine ring
glutamine, glycine, CO2, aspartate and two 1 carbon fragments from the 1 carbon folate pool
how many high energy phosphate bonds are needed for the synethsis of IMP?
6
what step in IMP synthesis is considered the rate limiting and regulated step?
the 1st step
how many steps in IMP synthesis require folate?
2
how many steps in IMP synthesis can be blocked by azaserine?
2
what is azaserine an analog of?
glutamine
what does azaserine block?
the amide transfer from glutamine
what are sulfonamides an alalog of?
p-aminobenzoic acid
what do sulfonamides block?
the biosynthesisi of folic acid- so blocks nucleotide synthesis
how is de novo synthesis of purine nucleotides regulated?
feedback inhibition
what 3 compounds block the enzymes PRPP synthetase and PPRP amidotransferase? (enzymes that catalyze the 1st two steps of IMP synethsis)
IMP, GMP, AMP
what is the function of HGRT?
catalyzes the formation of nucleotides from either hypoxanthine or guanine. This enzyme is inhibited by IMP and GMP
what is the function of ARPT?
catalyzes the formation of AMP from adenine- inhibited by AMP
is this statement describing purines or pyrimidines?
the ring is formed THEN it reacts with PRPP to form the nucleotide
pyrimidines
what are the 2 precursors to the pyramidine ring?
carbamoylphosphate & asparate
what do patients with OTC deficiencies build up high levels of pyrimidines in their serum & urine
because in OTC carbamoyl phosphate builds up and this is a precursor for the synthesis of pyramidines
what is orotic aciduria?
genetic disorder of pyrmidine biosynthesis
how can orotic aciduria be alleviated?
by feeding of uridine or cytidine→this supplies the body with the needed pyrimidine bases and inhibits CP II
what is substrate channeling?
when 1 enzyme passes its product right off to the next to use as a substrate
list the 6 enzymes that are inhibited by azaserine
- CPSII
- CTP synthase
- FGAR aminotransferase
- GMP synthase
- PRPP aminotransferase
- Aorargine synethase
when are deoxynucleotides made?
during DNA replication
what drug inhibits ribonucleotide reductase?
hydroxyurea
what is the enzyme ribonucleotide reductase needed for?
in the formation of deoxynucleotides
what reaction does thymidylate synthase catalyze? what form of THF is needed for this rxn?
dUMP–> dTMP
N5N10 methyleneTHF
how is THF regenerated after the pathway that forms deoxyribonucleotides?
the enzyme dihydrofolate reductase which requires NADPH
what drug inhibits dihydrofolate reductase? thereby inhibiting the regeneration of THF
methotrexate
what is the function of 5-fluorouracil?
blocks the transfer of the methylene group to the pyrimidine ring
what are the 2 ways that AMP can be degraded?
- Can first be deaminated to IMP→ then hydrolyzed to inosine
- Or can be hydrolyzed to adenosine then demaminated to inosine
how is GMP degraded?
it is hydrolyzed to guanosine
how is CMP degraded?
can be deaminated to UMP and then hydrolyzed to uridine-or it can be hydrolyzed to cytidine and then deaminated the uridine
what is the final product of purine degradation?
uric acid
what is the enzyme xanthine oxidase
enzyme required for breakdown of AMP and the oxidation to uric acid contains molybdenum (only known function in the human body of this element)
what is the final product of pyrimidine degradation?
uracil: B-alanine
thymine: B- aminoisobutyrate
what is the cause of gout?
caused by precipitation of sodium urate crystals in the joints & kidneys
what are the 2 circumstances that can cause gout?
- abnormal PRPP synthetase and not responsive to feedback inhibition
- HGPRT deficiency leads to increased PRPP levels (so greater de novo synthesis of purines)
what is the treatment for gout?
allopurinol (which blocks the production of uric acid)
what is lesch nyhan syndrome?
X linked recessive condition due to severe or complete deficiency of HGPRT
what are the symptoms of lesch nyhan syndrome?
Hyperuricemia, gout, urinary tract stones and neurological symptoms (mental retardation, spasticity and self mutilation)
what is the treatment for lesch nyhan sydrome?
can use allopurinol to reduce the uric acid formation but it does NOT alleviate the neuro symptoms
Can also be treated with: low protein diet, cochicine and a low purine diet
what is the cause of adenosine deaminase deficiency?
deoxyadenosine & adenosine are abundant and are not degraded but are efficiently converted to nucleotides in white blood cells
High levels of dATP inhibit ribonucleotide reductase which inhibits DNA synethsis- so the WBCs
what is the treatment for adensoine deaminase deficiency?
bone marrow transplantation & enzyme replacement therapy
Gene therapy has been experimented
