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41 Cards in this Set
- Front
- Back
Nucleoside vs Nucleotide? (P.353)
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Nucleoside is a glycosidic cmpd attached to a pentose sugar.
Nucleotide is an ester cmpd with a sugar and phosphate group attached. |
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Re Purines and Pyrimidines, at what positions do they differ? (P.353)
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Purines differ only at positions 2 and 6.
Pyrimidines differ at positions 4 and 5. |
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What is the precursor to all of the purines? Pyrimidines? (P.353)
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Purines = Hypoxanthine
Pyrimidines = Uracil |
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In purines, where is the pentose typically attached? Pyrimidines? (P.354)
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Purines = C9
Pyrimidines = C1 |
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Where is the phosphate group typically added in the pentose sugar?
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C5
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Three sites of modification occur in pentose sugar. What are the locations and what happens there?
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C1 = glycosidic linage
C2 = oxy or deoxy occurs here C5 = Phosphates |
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Phosphates can be labelled alpha, beta, or gamma - which one is alpha?
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Alpha = closest to pentose ring.
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Cancer treatments often target this pathway: (P.355)
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Nucleotide metabolism
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What is the starting compound in purine de novo synthesis? What is the final compound before a branch point is reached? (P.355)
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PRPP = starting material
IMP = final cmpd before branching occurs |
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What 4 aa's are used in purine nt synthesis and what doe they contribute? (P.355)
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Glutamine (1N), Glycine (1N, 2C), Glutamine (1N) and Aspartate (1N)
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how many ATP are required to make purine? (P.355)
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5 (4 for energy plus the original precursor molecule PRPP)
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How many carbon and nitrogens does glycine contribute? (P.355)
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2Cs and 1 N
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What does chemo drugs typically target in purine pathway? How many "formylations" does the purine synthesis rxn use and what doe they contribute?? (P.355)
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Tetrahydrofolate - uses two THF, each contributing 2 Cs
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How many CO2 molecules does the purine synth pathway use and how many Cs does it contribute?
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1 CO2 and 1 C
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When purine synthesis reaches IMP, the pathway branches - what do the two branches make?
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AMP and GMP
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What aa does the AMP branch use? How/where is IMP modified? What is its energy requirement? (P.356)
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AMP uses Aspartate; Oxygen at position 6 of IMP is replaced with amino group; Requires GTP
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What aa does the GMP branch use? How/where is IMP modified? What is its energy requirement? (P.356)
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GMP uses Glutamine; Amino group is added at IMP position 2. Energy requirement is ATP
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Where does the D-ribose-5-phosphate precursor to PRPP come from?
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Pentose phosphate pathway
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D-ribose-5-phosphate to PRPP via PRPP synthetase is NOT the committed step on de novo purine synthesis. Why? (p. 356)
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Bc PRPP can be used in other pathways and is not strictly used for purine nt synthesis.
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Overexpression of PRPP synthetase or increased enzymatic activity with altered kinetic properties has been documented in small subsets of what population?
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Gouty pts
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What enzyme is involved in the committed step on purine synthesis? What does it do? (p 357)
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ATase (Amidophosphoribosyltransferase). It desplaces pyrophosphate with the amino group of glutamine.
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How is ATase regulated (p 357)
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It is a dimer with its active site hidden. When PRPP is high enough, it induces monomerization and allows catalytic activity. When it purine nts get high enough, ATase is induced to dimerization/inactivation.
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What are the three multifunctional enzymes that are used in purine synthesis? Why does nature use these?
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GART, AIRC and Adenylosuccinate lyase. These enzymes are potentially used for three reasons:
1. Unstable intermediates 2. Efficiency 3. Toxic intermediates |
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Synthesis and interconverstion of nucleoside diphosphates and triphosphates are mediated by different kinases. Which are base-specific and which are broadly specific? (p358)
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Monphosphate kinases are base-specific (Eg Adenylate Kinase and Guanylate Kinase). Diphophate kinases are broadly specific.
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Adenylate cyclase is important bc it regulates the ratio of ATP, ADP and AMP to what? (p358)
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100:10:1, respectively
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Review figure on p 359 for says that purine synth is regulated
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Review figure on p 359 for says that purine synth is regulated
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What are the three key rxn in catabolysis of purine nts?
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1. Dephosphorylation
2. Deamination 3. Phosphorolysis |
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In the first step of AMP degradation, two paths can be taken - this results in ?? or ?? Why is this important? (p359)
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IMP or Adenosine. IMP is produced in exercising skeletal muscle and facilitates the net resynthesis of ATP following exercise. Adenosine is produced in ischemic or anoxic heart - it is a potent coronary vasodilator that facilitates oxygen delivery back to damaged tissue.
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Memorize basic degradation pathway on pg 359?
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Memorize basic degradation pathway on pg 359?
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How does ischemia cause increase production of free radicals?
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XDH and XO are used to convert hypoxanthine to uric acid. Under ischemic conditions, XDH is converted to XO and XO uses O2 to produce Xanthine and hydrogen peroxide as a byproduct. The H2O2 is toxic
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What are the three ways someone can have Primary Gout? (p361)
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1. Overexpression of PRPP
2. Deficiency of HPRT salvage pathway enzyme 3. Urate excretion deficiency |
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What two things can cause Secondary Gout?
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1. Drug intake
2. Unusual dietary habit |
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What is allopurinol and what is the mechanism by which it works? (p361)
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It is an analogue of hypoxanthine that inhibits XDH (xanthine dehydrogenase). This shunts excess hypoxanthine through the salvage pathway, increases nts that inhibit ATase and therefore urate.
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Second to Urate, what is the most insoluble purine base in the body? What deficiency causes this? How is accumulation of this compounded treated?
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Xanthine. Excess caused by a deficiency in Xanthine Dehydrogenase. Only way to reduce this is via diet.
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What two deficiencies cause SCID?
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Adenosine Deaminase (ADA) and Purine nucleoside phosphorylase (PNP).
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What is the mechanism by which ADA and PNP cause SCID?
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dATP or dGTP accumulates in lymphocytes. This excess inhibits ribonucleotide reductase responsible for producing all of the dNTPs necessary for DNA synthesis.
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What are the two ways that purine nucleotides can be produced in the salvage pathway? How much energy is required? (p363)
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1. a) Adenine phosphoribosyltransferase (APRT) attaches PRPP directly to adenine to produce AMP
b) Hypoxanthine-guanine phosphoribosyltransferase (HPRT) can add PRPP directly to Hypoxanthine or Guanine to produce IMP or GMP, respectively. 2. ATP can be directly attached to a purine nucleoside. **Both require 1 ATP vs 5 |
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In Lesch-Nyhan syndrome, what pathway is defective and what enzyme is deficient? (p364)
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Salvage pathway is defective and caused by deficiency in HPRT
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What is the inheritance of Lesch-Nyhand syndrome? (p364)
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X-linked
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With a deficiency in HRPT, what symptoms would you expect? (p364)
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You would expect a decrease in salvage pathway shunting and an increase in Urate and therefore gout. There would also be an increased rate of PRPP synthesis and de novo purine synthesis.
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A nice review of lecture 1
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A nice review of lecture 1
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