Nucleotide Metabolism (Purines) Flashcards
•Identify the differences between N-base, nucleoside and nucleotide with examples •Regarding purinebiosynthesis –Enumerate the C & N donors of the purinering (amino acids and 1-C groups) –Outline purinebiosynthesis –Discuss the regulation of purinebiosynthesis (Identify the regulatory enzyme and positive and negative modulators) –Correlate the mechanism of action of sulfadrugs, trimethoprim, methotrexate, mycophenolicacid to their clinical application –Explain the formation of deoxyribonuc
What is the base found in Inosine Monophosphate (IMP), an intermediate in purine synthesis and degradation?
Hypoxanthine
Which base is found in xanthosine MP, an intermediate in purine synthesis and degradation?
Xanthine
Unusual bases found mainly in tRNA, but also in viral DNA, are often _________ of the major bases.
Methyl derivatives
Addition of a _________ to the base produces a nucleoside.
pentose sugar
The phosphate groups in nucleotides are responsible for the ___________associated with RNA and DNA.
negative charges
Purine nucleotide synthesis has two pathways. What are they?
De Novo
Salvage
In humans, all of the enzymes necessary for de novo purine synthesis are found in the __________of the cell.
cytoplasm
Before purine synthesis can take place____________ , is produced from __________ and ________by _________.
5-phosphoribosyl-1-pyrophosphate (PRPP)
ribose-5-phosphate
ATP
ribose phosphate pyrophosphokinase
What reaction does PRPP synthetase catalyze?
Ribose - 5 - phosphate to 5-Phophoribosyl-1-pyrophosphate
The first step of de novo purine synthesis is the committed and rate-limiting step. This reaction converts PRPP —> 5-phosphoribosylamine using which enzyme?
Glutamine:phosphoribosyl pyrophosphate amidotransferase
The rate of the reaction catalyzed by Glutamine:phosphoribosyl pyrophosphate amidotransferase is controlled by the intracellular concentrations of what?
Glutamine and PRPP
The rate of the reaction catalyzed by Glutamine:phosphoribosyl pyrophosphate amidotransferase is inhibited by what?
AMP
GMP
IMP
How would you describe megaloblastic anemia?
Folate deficiencies in which hemoglobin levels are low and the bone marrow shows abnormally high numbers of megaloblastic cells (large abnormal immature erythrocytes)
Cancer cells can become resistant to MTX by amplification of the gene for what enzyme?
dihydrofolate reductase.
Synthesis of AMP from IMP requires…
GTP (adenylosuccinate synthetase)
Synthesis of GMP from xanthosine monophosphate requires …
ATP(GMP synthetase)
The nucleotide monophosphates (NMP) are finally converted to NDP and NTP by __________and ____________, respectively.
nucleoside monophosphate kinases (base specific)
nucleoside diphosphate kinases
Mycophenolic acid is an inhibitor of what enzyme?
Inosine monoposphate dehydrogenase
(T/F) Purines that result from normal turn over of cellular nucleic acids or that are obtained from the diet and not degraded can be salvaged
True
Purine salvage involved which two enzymes?
Hypoxanthine-guanine phosphoribosyltransferase (HGPRT)
and
Adenine phosphoribosyltransferase (APRT)
Hypoxanthine is converted to IMP in thr purine salvage pathway by what enzyme?
HGPRT
Guanine is converted to GMP in the purine salvage pathway by which enzyme?
HGPRT
Which reactions use HGPRT?
Hypoxanthine –> IMP
Guanine –> GMP
Adenine to AMP in the purine salvage pathway is catalyzed by which enzyme?
APRT
What type of disorder is Lesch-Nyhan syndrome? Resulting from a deficiency of what enzyme?
X-linked
HGPRT
Lesch-Nyhan Syndrome results in an inability to do what?
Salvage the purines:
Hypoxanthine and
Guanine
What is the end product of degredation of hypoxanthine and guanine in Lesch-Nyhan?
Uric Acid
_______ are often found in the diapers of infants with Lesch-Nyhan Syndrome
Orange crystals
A patient who comes to you with severe mental retardation, self-mutilation, involuntary movements, and gout most likely has what syndrome?
Lesch-Nyhan
Lesch-Nyhan Syndrome causes increased _______levels and an increase in ______
PRPP
de novo purine synthesis
Most purines in the diet are degraded to _______ rather than salvaged.
uric acid
While purines are degraded to ________, pyrimidines are ________ and returned to _______
-uric acid
-absorbed in the intestinal mucosa
-the circulation.
Adenosine deaminase (ADA) deficiency causes a type of ____________, involving _______ and _______ depletion. (______________)
-Severe combined immunodeficiency (SCID)
-T-cell
-B-cell
(Lymphocytopenia)
Why does ADA deficiency produce lymphocytopenia?
DNA is not synthesized in T-cells and B-cells because of an accumulation of dATP
In ADA deficiency, _______ and ______ are better substrates for purine nucleoside phosphorylase than is adenosine.
Guanosine
Inosine
In ADA deficiency, dATP accumulates and causes inhibition of which enzyme?
Ribonucleotide reductase
Purine nucleoside phosphorylase (PNP) deficiency causes impairment of the function of what?
T-cells
Decreased uric acid production and increased purine nucleoside and nucleotide production is characteristic of what?
PNP deficiency
Lab tests of a patient in your care return showing hyperuricemia and acute arthritic joint inflammation caused by deposition of uric acid crystals. This patients most likely has which disorder?
Gout
What characterizes Primary Gout?
-Genetic
-Affects mainly males over 30
What characterized Secondary Gout?
Brought on by a number of disorders including:
-Leukemia
-Polycythemia
-HGPRT deficiency
-treatment of cancer with antimetabolites
-Chronic renal insufficiency
Gout can be diagnosed by the presence of negatively birefringent ____________ crystals in aspirated synovial fluid examined by polarized-light microscopy
monosodium urate
PRPP synthase is also known as what?
Ribose Phosphate Pyrophosphokinase
