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44 Cards in this Set

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Purine/Pyrimidine
What are the overall anabolic and catabolic pathways involved in nucleotide synthesis?
Anabolic - AMP, GMP, TMP, UMP, CTP, Purine/pyrimidine synthesis, Salvage.
Catabolic - Purine->Uric acid, Pryrimidine->Beta alanine and beta aminoisobuturate
Purine/Pyrimidine
What major difference is there between purine and pyrimidine synthesis in terms of when and how the ring is added? Molecule they have in common?
Pyrimidine - ring added first then sugar base
Purine - Sugar base first then the ring
Molecule - PRPP
What molecule is utilized in the start of the purine synthesis pathway? What molecule is formed by the purine synthesis pathway? What is the name of the enzyme the catalyzes the addition of the first component of the purine ring? What nitrogen containing amino acid donates this first part of the ring?
Start - Ribose-5-Phoshate
Formed - IMP
Enzyme - PRPP Synthetase
AA - Glutamine
How many enzymatic steps are required to synthesize IMP from PRPP in humans? What is the cellular location of all these enzymes?
IMP - 10 steps
Location - Cytosol
What carrier is utilized in 2 different steps to add to the ring? What vitamin is it derived from? What atom does it donate?
Carrier - N10-Formal THF
Vitamin - Folate
Atom- Carbon
Purine/Pyrimidine
What is the name of the enzyme required to turn folate into the form used in purine synthesis? How many steps are required for this enzyme to carry out its job? What does this enzyme do? Where in P/P metabolism does inhibition of this enzyme have an effect?
Enzyme - DHFR
Steps - 2
Action - convert double bonds to single bonds which converts DHF into THF
Inhibition - MTX inhibits DHFR which inhibits Purine formation which inhibits TMP which interferes with DNA synthesis and AA metabolism
Purine/Pyrimidine
What pathway is most affected by sulfa drugs?
Bacterial purine synthesis
Purine/Pyrimidine
What nucleotides are formed from IMP?
AMP, GMP
Purine/Pyrimidine
What is the only enzyme that is known to be regulated in the steps of forming IMP from PRPP? What are the allosteric activators of this enzyme? What are the allosteric inhibitors?
Enzyme - Glutamine PRPP Amido transferase
Allosteric activator- PRPP
Allosteric inhibitor - IMP, AMP, GMP
Purine/Pyrimidine
What is the allosteric inhibitor of adenylosuccinate synthetase? What is the allosteric inhibitor of IMP DH?
AOS - AMP
IMP DH - GMP
Purine/Pyrimidine
Thio-IMP is a ____ inhibitor of Glutamine PRPP Amido Transferase? Thio-IMP is a ____ inhibitor of adenolosuccinate synthetase and IMP DH?
Allosteric
Competitive
Purine/Pyrimidine
Can 6MP be incorporated into DNA?
Yes to an extent, disrupts replication
Purine/Pyrimidine
What are reactants and products of HGPRT? What are the reactants and products of APRT? What disease arises because of HGPRT deficiency? What is the reason for the increase in uric acid levels? Usually cause of death?
HGPRT - Guanine->GMP, Hypoxanthine->IMP
APRT - Adenosine->AMP
Deficiency - Lesch Nyhan Syndrome
Uric acid - Glu PRPP Amido transferase deficiency causes build up of PRPP which makes more purines which degrade to increase uric acid.
Death - Kidney failure renal deposits
Purine/Pyrimidine
If there were no selvage pathways in Purine metabolism would 6MP be effective as a cancer chemotherapeutic?
No because it is dependent on it (uses HGPRT). 6MP inhibits novo synthesis which blocks purine synthesis; 5-FU is independent
Purine/Pyrimidine
6MP is a precursor to what inhibitory molecule?
Thio-IMP (6MP does not inhibit enzymes)
Purine/Pyrimidine
How many enzymatic steps are required to synthesize OMP from glutamine and PRPP in humans? What is the cellular localization of all but one enzyme?
5
Cytosol 1 in mito
Purine/Pyrimidine
What cytosolic enzyme that catalysis ATP requiring step of pyrimidine synthesis has an analogous mitochondrial enzyme that participates in the urea cycle? What is the enzyme that catalysis the first step in pyrimidine synthesis? What are the important differences between the cytosolic and mito enzymes? What is an enzyme of pyrimidine synthesis found only in mito? Why is it advantageous that is is a mito enzyme?
CPS2
CPS2
Cytosolic CPS2 which is inhibitable and uses gluatmine.
Mito CPS1 not inhibited and uses NH4.
Only Mito - DihydroOrotate DH
Advantage - Uses and NAD+ubiquinons
Purine/Pyrimidine
Why does excess ammonia lead to elevated levels of Orotic acid in urine? And why does this primarily involve the liver?
In liver, excess ammonia increases CPS1 and that leads to overall increase in orotate!
Purine/Pyrimidine
What enzyme is present at low levels in ecoli lab strains that account for the relative safety of these strains for use in recombinant DNA work? What does the low enzyme expression mean for the ability of the bacterium to survive in the wild?
OPRT
Survive - (Low survival needs ORPT to survive) Bacteria cant use salvage pathway
Purine/Pyrimidine
What are the sources of carbon and nitrogen atoms in pyrimidine ring?
Most carbons and 1 Nitrogen from aspartate other Nitrogen from glutamine other carbon from HCO3 or CO2
Purine/Pyrimidine
What molecule is directly formed from the prymidine synthesis pathway?
UMP
Purine/Pyrimidine
How is the pyrimidine synthesis pathway like a salvage pathway?
Adds base to ring
Purine/Pyrimidine
Are other pyrimidine bases than Orotate salvaged? Why are salvage pathways useful?
Yes, Uricil and thyomine.
Useful because less ATP needed.

*cytosine not salvaged*
Purine/Pyrimidine
What purine triphosphate activates pyrimidine synthesis?
ATP
Purine/Pyrimidine
How is cytidine monophosphate (CMP) formed?
UMP->UDP->UTP->CTP->CDP->CMP
Purine/Pyrimidine
What purine triphosphate allosterically activates pyrimidine synthesis?
ATP
Purine/Pyrimidine
How is TMP formed?
UMP->dUMP->TMP

UMP>dUMP by ribonucleotide reductase
dUMP>TMP by Thymidylate Synthase
Purine/Pyrimidine
What carrier donates a carbon to form TMP from dUMP? What is the enzyme that catalysis the rxn?
N5N10Methyline THF
Enzyme - Thymidylate Synthase
Purine/Pyrimidine
If there were no salvage pathways in pyrimidine metabolism would 5-FU be affective as a cancer chemtherapeutic?
No because 5-FU needs to be converted to FdUMP (No salvage=no FdUMP
Purine/Pyrimidine
5-FU is a precursor for what inhibitory molecule?
FdUMP (5FU does not inhibit enzymes)
Purine/Pyrimidine
What type of inhibition does FdUMP have on thymidylate synthase?
Suicide inhibitor
Purine/Pyrimidine
Can 5-FU be incorporated into DNA if so what are the effects?
Yes decreasing RNA processing

(only as FdUMP, not as 5-FU)
Purine/Pyrimidine
What are some of the strategies cancer tumor cells have been observed to employ to exhibit resistance to MTX?
decrease uptake of methotrexate; also increase exocytosis of methotrexate; dhfr decreases affinity for methotrexate so tumor cells create more dhfr and decrease its degradation to increase resistance to methotrexate.
Purine/Pyrimidine
What is the mechanism of ICI D1694? Since ICI D1694 resembles MTX how are side effects related?
Inhibits Thymidylate synthase directly
Fewer side effects and more selective
Purine/Pyrimidine
How is the use of Leucovorin with MTX different from the use of Leucovorin with 5FU?
Leucovorin is antidote for MTX but increase effect of 5FU
Purine/Pyrimidine
What do nucleotide kinases do?
What do nucleoside diphosphate kinases do? This can also be done for what nucleotide by glycolysis or oxphos?
nucleotide nMP->nDP
nucleoside di nDP->nTP
Adenine
Purine/Pyrimidine
What is the name of the enzyme that converts ribonucleotides to deoxyribonucleotides? What molecule does the reducing power come from originally? What form (#Pi) are the ribonucleotides in before conversion?
Ribonucleotide reductase
NADPH
Diphosphate form
Purine/Pyrimidine
What class of enzymes break nucleic acids down into nucleotides? What class of enzyme removes phosphates from nucleotides (converting them to nucleosides)? What class of enzymes breaks nucleosides into bases and sugars?
Neuclotides - Nucleases
Neucleosides - Nucleotidases
Base and sugar - Nucleoside phosphorylasis (PNP)
Purine/Pyrimidine
What muscular enzyme deaminates Adenine nucleotide (skeletal muscle)? What enzyme in other tissues deaminates Adenosine nucleoside? What is the difference in terms of the order in which the Pi and the N groups are removed?
AMP deaminase
Adenosine deaminase (ADA)
????
Purine/Pyrimidine
What is the name of the heterogenous base attached to IMP?
Hypoxanthine
Purine/Pyrimidine
What is the nitogenous product of purine degradation that is excreted?
Uric acid from xanthene by xanthene oxidase
Purine/Pyrimidine
What is gout? What are some of the underlying causes of gout?
Gout - Inc in uric acid, precipitation of crystals in big toe and kidney caused by inc PRPP which inc GTP and ATP which inc degradation which inc Uric acid caused by dec in glycogen synthesis which inc glucose in PPP which inc PRPP.
Under excretion of uric acid.
Purine/Pyrimidine
What do alopurinal and rasburicase do? In what why is rasburicase superior?
Treat uric acid precipitation.
Alopiurinal inhibits XO, rasburicase degrades uric acid making it superior but it must be injected and it is expensive therefore usually only used in addition to cancer treatment.
Purine/Pyrimidine
Degredation of cytosine, uracil, and thyamine have what 2 degradation products in common? What other degradation end product results from catabolism of cytosine and uracil? What end product results from catabolism of thyamine?
CO2 NH4
Uracil and cytosine->BetaAlanine
Thyamine->BetaAminoIsobuterate