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- Purine Metabolism
Purine Metabolism
Pharmacy 411 with Jorvig at Roseman University of Health Sciences
About this deck
By: Jon Warta
Created: 2011-09-29
Size: 48 flashcards
Views: 22
Created: 2011-09-29
Size: 48 flashcards
Views: 22
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Two methods of purine anabolism
de novo synthesis
purine salvage pathway
What cellular functions are nucleotides required for?
- replication
- transcription
- energy metabolism
- physiological mediators (cAMP, cGMP)
- components of coenzymes (NAD, FAD)
- allosteric modulators
Three components from which purines are synthesis
amino acids
tetrahydrofolate
CO2
Can red blood cells conduct de novo purine synthesis?
no
De novo synthesis of both AMP and GMP goes through what common intermediate?
inosine monophosphate (IMP)
De novo synthesis and all salvage pathways use a common reactant called
phosphoribosylpyrophosphate (PRPP)
PRPP is synthesized from
5-phosphoribose in the pentose phosphate pathway
PRPP synthesis is activated by:
high levels of inorganic phosphate (lots of ATP used)
PRPP synthesis is inhibited by:
other nucleotides
ribose-5-phosphate + ATP ----->
PRPP + AMP
De novo purine synthesis begins with the synthesis of:
5-phosphoribosylamine (PRA)
What is the committed step of de novo purine synthesis?
PRA synthesis
What is the rate-limiting step for purine synthesis?
PRA synthesis
PRPP is a(n) ____________ of PRA synthesis
activator
IMP, GMP, and AMP are _______________ of PRA synthesis
synergistic inhibitors
There is no regulation of IMP synthesis after which step?
PRA synthesis
Identify all origins in slide 19.
see slide 19!
What is the common precursor to AMP and GMP?
IMP
_______ inhibits AMP synthesis and _________ inhibits GMP synthesis
AMP, GMP
Synthesis of AMP requires _____________ for energy
GTP
Synthesis of GMP requires ______________ for energy
ATP
Slide 23
slide 23
Purine NTPs are formed from either AMP or GMP by the action of:
nucleoside 5'-monophosphate kinases
nucleoside 5'-diphosphate kinases
valacyclovir is a prodrug attached to the amino acid ____________
valine
The kinase which begins activation of acyclovir is actually a viral enzyme called:
thymidine kinase, phosphorylates acyclovir to its monophosphate form, cellular kinases convert to triphosphorylated, which is active against DNA synthesis
Two enzymes responsible for nucleobase salvage:
hypoxanthine-guanine phosphoribosyl transferase (HGPRT)
adenine phosphoribosyl transferase (APRT)
both catalyze the reaction of their nucleobases with PRPP to give the nucleotide
HGPRT is inhibited by:
IMP, GMP
APRT is inhibited by:
AMP
How does use of the purine salvage pathway inhibits the de novo synthesis pathway?
- lowers PRPP level
- raises purine NTP level
Enzyme that phosphorylates the 5' position of adenosine to give AMP:
adenosine kinase
catalyzes the reaction of GMP to IMP
GMP reductase
catalyzes the reaction of AMP to IMP
AMP deaminase
AMP conversion to IMP is inhibited by ___________ but enhanced by ____________
GTP and GDP, ATP
GMP conversion to IMP is strongly inhibited by ____________ but enhanced by ____________
XMP, GTP
The catabolism of purines follows a common path to _____________
uric acid
What regulates purine catabolism?
nothing, it is unregulated
Enzymes that catabolize nucleic acids to nucleotides
nucleases
Guanine catabolism:
GMP --> guanosine --> guanine --> xanthine --> uric acid
Adenine catabolism:
AMP --> either IMP or adenosine --> inosine --> hypoxanthine --> xanthine --> uric acid
Enzyme that converts xanthine to uric acid
xanthine oxidase
What is hyperuricemia?
uric acid is overproduced and blood and urine concentrations are elevated
What is gout?
- a defect in purine metabolism
- hyperuricemia
- uric acid is poorly soluble, formed sodium urate crystals, deposited in joints, kidney
What are some causes of gout?
- increase in de novo synthesis
- decrease in purine salvage
- increase in purine catabolism
What is a drug used to treat gout?
allopurinol (Zyloprim)
What is allopurinol's method of action?
xanthine oxidase inhibitor
Hypoxanthine + PRPP -->
IMP
catalyzed by HGPRT
Guanine + PRPP -->
GMP
catalyzed by HGPRT
Adenine + PRPP -->
AMP
catalyzed by APRT
About this deck
By: Jon Warta
Created: 2011-09-29
Size: 48 flashcards
Views: 22
Created: 2011-09-29
Size: 48 flashcards
Views: 22
About StudyBlue
STUDYBLUE makes things that make you better at school.
Things like online flashcards with photos and audio.
Things like personalized quizzes and friendly reminders about when (and what) to study next.
Think of it as a digital backpack™: access to all of your study materials online and on your phone.
STUDYBLUE exists to make studying efficient and effective for every student, for free. Join us.
“I have been getting MUCH better grades on all my tests for school. Flash cards, notes, and quizzes are great on here. Thanks!”
Kathy
Kathy