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Block 6 purine and pyrimidine metabolism

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Question
Answer
What disease has a complusive drive to self-injure?   Lesch-Nyhan  
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How is Lesch-Nyhan acquired?   X-linked caused by a single point mutation  
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What are clinical signs of Lesch-Nyhan?   "orange sand" or uric acid crystals passed from kidneys  
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What are the three component structures of a mononucleotide?   Nitrogen containing base, carbohydrate (ribose or deoxyribose), a phosphate moiety  
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Where do the N bases come from for purine and pyrimidine metabolism?   De novo synthesis or salvaged pathway  
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What three amino acids are very important as Nitrogen sources for purines and pyrimidines?   aspartate, glutamine, glycine  
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What provides the Ribose for pyrine and pyrimidine pathways?   Hexose monophosphate pathway (HMP)  
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Is the salvage pathway more important for purines or pyrimidines?   Purines are bicyclic - this means they are more complicated and require more energy to produce.  
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What are three key roles for nucleotides in a living organism?   DNA & RNA Energy Transfer reactions (ATP, etc) water soluble vitamins all have adenosine nucleotides= NAD, FMN, FAD, CoA  
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What is the limiting factor in purine or pyrimidine synthesis?   the nitrogen base  
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What is the common enzymatic feature of both de novo and salvage?   utlilize ribose 5-P via HMP activated by PRPP synthetase to PRPP (phospho-ribosyl-pyrophosphate  
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What type of molecule is PRPP?   phosphoribosyl-pyrophosphate is an activated sugar  
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What tissue must rely exculsively on the salvage pathway because de novo is not possible?   Brain tissue  
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What enzyme is defective in Lesch-Nyhan? This limits the tissues how?   HGPRT - hypoxanthine-guanine-phospho-ribosyl-transferase.. Tissues such as brain cannot synthesize purine mononucleotides for RNA synthesis  
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If HGPRT is not expressed what symptoms arise?   CNS deterioration Mental retardation Hyperurcemia and gouty arthritis compulsive self-mutilation pig herding  
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What enzyme is needed to start the de novo synthesis of Pyrimidines?   Carbamoyl Phosphate Synthetase-2  
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What are the starting products acted upon by carbamoyl phophate synthetase-2 to create carbamoyl phosphate?   Uses CO2 + Glutamine + ATP  
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What do you add to carbamoyl phosphate to get an intermediate, ortic acid, that will be acted upon by PRPP synthetase?   aspartate  
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What does PRPP synthase give off?   Gives of CO2 to leave a UDP which is converted by the third important enzyme  
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What enzyme of pyrimidine synthesis frees O2 from hydroxyurea to yeild what?   Ribonucleotide Reductase converts hydroxyurea to UDP,  
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What enzyme is inhibited by fluoroucil? What is it's use   thymidylate synthase takes deoxygenated uridylmonophosphate to dTMP.  
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The three important enzymes of pyrimidine synthesis are what?   Ribonucleotide reductase Thymidylate synthetase Dihydrofolate reductase  
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What reduces NDPs to dNDP for DNA synthesis? What inhibits this enzyme?   Ribonucleotide reductase which is inhibited by hydroxyurea  
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What methylates dUMP to dTMP, but requires Tetrahydrofolate (THF)? What inhibits it?   Thymidylate synthetase inhibited by 5FU  
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What converts dihydrofolate to THF for the methylation reaction of thymydylate synthetase? Inhibited by?   dihydrofolate which is inhibited by Methotrexate  
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What drugs can arrest the growth of rapidly growing cells? How?   5FU (5-flourouracil) and methotraxate block synthesis of dTMP  
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What is the most important enzyme in purine synthesis (de novo)   PRPP amidotransferase catalyses the first, rate-limiting reaction  
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What drug can be prescribed to help a gout or hyperuracemia patient? Why?   Allopurinol inhibits xanthine oxidase  
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What drug helps cancer patients by inhibiting PRPP amidotransferase?   6-mercaptopurine nucleotide  
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eating a lot of what contributes to the build up of mononucleotides and what condition?   Lots of foods rich in purines, such as asparagus and organ meat leads to gout  
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IF you have an Adenosine deaminase deficiency what condition results? How is it acquired?   autosomal recessive condition that causes SCID - severe combined immunodeficiency  
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What is ADA deficiency defect and symptoms?   adenosine deaminase defective, allows adenosine and amp to accumulate: causes Severe Immunodeficiency (SCID)the B and T lymphocyte disfunction  
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Gout can be caused by deficiency in two enzymes we studied. What are they?   Glucose-6-P phosphatase = Von Gierke HGPRT  
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How does allopurinol react?   non-competitive inhibitor of xanthine oxidase  
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