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55 Cards in this Set
- Front
- Back
What makes up a Nucleotide?
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-Nitrogenous Base
-Pentose Monosaccharide -Phosphate Groups (1,2, or 3) |
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Describe the Composition of Purines.
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2 Rings Fused Together
-5-Membered Ring -6-Membered Ring |
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Describe the Composition of Pyrimidines.
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Single, 6 Membered Ring
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Which Nucleotides are Purines?
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Pure As Gold
-Adenine -Guanine |
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Which Nucleotides are Pyrimidines?
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CUT they Py
-Cytosine -Thymine (Uracil in RNA) |
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What is a Nucleoside? How is this different from a Nucleotide?
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-Base + Pentose
-Nucleoside = Nucleotide - Phosphate Groups |
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What types of Pentose Sugars are usually found attached to Nucleotides and Nucleosides?
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-Ribose
-2-Deoxyribose |
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What type of Bond forms when a Nucleoside binds with Phosphate? What does this result in?
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-Ester
-Nucleotide |
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How, in general (very), are purines synthesized?
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Series of Reactions that add Carbon and Nitrogen to Ribose 5-Phosphate
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What is PRPP? What role does it play in Purine Synthesis?
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-5-Phosphoribosyl-1-Pyrophosphate
-Synthesized in the 1st step of Purine Synthesis |
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How PRPP synthesized?
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-Ribose 5-Phosphate is Phosphorylated with 2 Phosphates
-ATP donates the Phosphates -Results in PRPP -Catalyzed by PRPP Synthetase |
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Which Enzyme catalyzes the Formation of PRPP?
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PRPP Synthetase
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What is the 1st step in the Synthesis of Purines? Describe this step.
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Formation of PRPP
-Ribose 5-Phosphate is Phosphorylated with 2 Phosphates -ATP donates the Phosphates -Results in PRPP -Catalyzed by PRPP Synthetase |
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What Activates PRPP Formation? Inhibits?
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-Activators – Phosphate
-Inhibitors – Purine Ribonucleotides (Negative Feedback) |
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What is IMP? How is it formed? When?
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-Inosine Monophosphate
-5'Phosphoribosylamine + 4 ATP > IMP -3rd Step in the Synthesis of Purines |
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Which step of Purine Synthesis do PABA Analogs act? What do they do?
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Inhibitors of Purine Synthesis
-PABA Analogs - Slow down formation of THF (In Bacteria, Coenzyme for many reactions) -Folic Acid Analogs (Methotrexate) - Inhibit Reduction of DHF to THF |
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What catalyzes the formation of IMP?
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THF
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What do Folic Acid Analogs do to Purine Synthesis? What effect do they have on all Cells? What are they used to Treat?
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-Inhibit Reduction of DHF to THF, which is used as a cofactor in many reactions
-Toxic to All Dividing Cells (especially fast dividing) -Used to Treat Cancer |
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What is IMP converted to before we can make Nucleoside Di and Triphosphates?
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AMP and GMP
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What role do AMP and GMP play in Purine Synthesis?
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Formed from IMP before Nucleosides can be formed
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What inhibits the formation of AMP and GMP
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The Product!!!! - AMP and GMP
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What the fuck is so cool about Mycophenolic Acid?
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Nothing (Another flashcard later/earlier)
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What the fuck is so cool about Mycophenolic Acid?
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-Reversible Uncompetitive Inhibitor of IMP Dehydrogenase
-Prevents Formation of GMP |
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What acts on IMP Dehydrogenase to prevent formation of GMP?
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Mycophenolic Acid
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What is Lesch-Nyhan Syndrome? How does it occur?
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-Deficiency of HGPRTase which catalyzes formation of Guanine
-Results in Increased PRPP, Less IMP and GMP, Increased De Novo Synthesis of Purines -Excess Production of Uric Acid |
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What is the Salvage Pathway's purpose?
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What do you think?
To salvage Nucleotides |
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What is disease is deficiency of HGPRTase associated with? What does it normally do?
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-Lesch-Nyhan Syndrome
-Deficiency of HGPRTase - Catalyzes formation of Guanine |
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What do we see an increase of if Lesch Nyhan Syndrome? Why?
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-PRPP
-Deficiency of HGPRTase - Catalyzes formation of Guanine |
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Excessive Production of Uric Acid is a feature in what disease?
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Lesch-Nyhan Syndrome
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How are Deoxyribonucleotides Synthesized? What is this Catalyzed by?
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-Basically we just remove a Hydroxyl Group from the Oxy Form
-Ribonucleotide Reductase and Thioredoxin Reductase |
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Were are Nucleic Acids Degraded? What do they form?
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-Small Intestine
-Uric Acid |
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What enzyme is responsible for the Breakdown of Purines in the pathway that will ultimately go to Uric Acid?
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Purine Nucleoside Phosphorylase
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What does Purine Nucleoside Phosphorylase do?
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Breaks down Purines to Products that will go to Uric Acid
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What happens if a patient has a Deficiency of Purine Nucleoside Phosphorylase?
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-Can't get to Hypoxanthine or Xanthine
-Excess Inosine and Guanin -Can't Produce Uric Acid |
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What does Adenosine Deaminase (ADA) do?
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Convert Adenosine to Inosine
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What enzyme converts Adenosine to Inosine?
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Adenosine Deaminase (ADA)
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What type of Cells usually have the highest activity of ADA?
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Lymphocytes
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What happens if a patient has a Deficiency of ADA?
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-Accumulation of Adenosine (Can't be converted to Inosine)
-Increased dATP Levels due to Adenosine Shunting -Inhibits Ribonucleotide Reductase -DNA Synthesis is Inhibited |
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What effects does ADA Deficiency have on the Immune System? Why?
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-DNA Synthesis is impaired
-Impairment of DNA Repair -Leads to Accumulation of DNA Breaks in the Cell Genome -Eventually Triggers Apoptosis of T and B Cells |
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What are some ways to Treat ADA Deficiency?
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-Bone Marrow or Stem Cell Transplants
-Injection of ADA -Gene Therapy |
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What is Gout? Why does it result?
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-High levels of Uric Acid in the Blood
-Due to Underexcretion or Overproduction |
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If a patient has Sodium Urate Crystals in their Kidney and/or Joints, what should you suspect?
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Gout
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What causes Gout?
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-Mutation in PRPP Synthetase Gene
-Defect in Purine Salvage Pathways -Alcohol |
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How do Mutations in PRPP Synthetase Genes result in Gout?
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-Results from Enzyme Resistance to Feedback from Purines
-Higher PRPP Levels -Leads to Increased Synthesis of Purines -High Levels of Uric Acid |
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How do Defects in Purine Salvage Pathways result in Gout?
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-Deficiency of HGPRTase
-Accumulation of Uric Acid |
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What are some symptoms of Lesch-Nyhan Syndrome?
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-Neurological Features
-Self-Mutilation -Involuntary Movements |
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What drugs are used to treat Gout?
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-Colchicine
-Allopurinol -Probenecid and Sulfinpyrazone |
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How are Pyrimidines Synthesized? How is this different from Purine Synthesis?
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-Synthesized before Addition of Ribose-5-Phosphate
-Not built upon it after Ribose-5-Phosphate Addition as for Purines |
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What are the 3 Steps in Pyrimidine Synthesis?
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-1 - Synthesis of Carbamoyl Phosphate
-2 - Synthesis of Orotic Acid -3 - Formation of Pyrimidine Nucleotide |
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What is the Committed Step in Pyrimidine Synthesis? What is it Catalyzed by?
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-Synthesis of Carbamoyl Phosphate
-CPS II - Carbamoyl Phosphate Synthetase II |
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What enzyme catalyzes the formation of Carbamoyl Phosphate?
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CPSII (Carbamoyl Phosphate Synthetase II)
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What is Orotic Aciduria? How does it result?
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-Deficiency in the Combination Enzyme that Metabolizes Orotate
-UMP Synthase is Deficient -Results in Accumulation of Orotic in the Urine |
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What happens if a patient is deficient in the enzyme UMP Synthase
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-Orotic Aciduria
-UMP is a Combination Enzyme that Metabolizes Orotate to Uric Acid -Results in Accumulation of Orotic in the Urine |
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How is dUMP converted to dTMP?
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Thymidylate Synthase
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What inhibits Thymidylate Synthase? What is this used to treat?
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-5-Fluorouracil
-Inhibits Tumor Growth |