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Block 6-purine pyri

Block 6 purine and pyrimidine metabolism

What disease has a complusive drive to self-injure? Lesch-Nyhan
How is Lesch-Nyhan acquired? X-linked caused by a single point mutation
What are clinical signs of Lesch-Nyhan? "orange sand" or uric acid crystals passed from kidneys
What are the three component structures of a mononucleotide? Nitrogen containing base, carbohydrate (ribose or deoxyribose), a phosphate moiety
Where do the N bases come from for purine and pyrimidine metabolism? De novo synthesis or salvaged pathway
What three amino acids are very important as Nitrogen sources for purines and pyrimidines? aspartate, glutamine, glycine
What provides the Ribose for pyrine and pyrimidine pathways? Hexose monophosphate pathway (HMP)
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.
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
What is the limiting factor in purine or pyrimidine synthesis? the nitrogen base
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
What type of molecule is PRPP? phosphoribosyl-pyrophosphate is an activated sugar
What tissue must rely exculsively on the salvage pathway because de novo is not possible? Brain tissue
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
If HGPRT is not expressed what symptoms arise? CNS deterioration Mental retardation Hyperurcemia and gouty arthritis compulsive self-mutilation pig herding
What enzyme is needed to start the de novo synthesis of Pyrimidines? Carbamoyl Phosphate Synthetase-2
What are the starting products acted upon by carbamoyl phophate synthetase-2 to create carbamoyl phosphate? Uses CO2 + Glutamine + ATP
What do you add to carbamoyl phosphate to get an intermediate, ortic acid, that will be acted upon by PRPP synthetase? aspartate
What does PRPP synthase give off? Gives of CO2 to leave a UDP which is converted by the third important enzyme
What enzyme of pyrimidine synthesis frees O2 from hydroxyurea to yeild what? Ribonucleotide Reductase converts hydroxyurea to UDP,
What enzyme is inhibited by fluoroucil? What is it's use thymidylate synthase takes deoxygenated uridylmonophosphate to dTMP.
The three important enzymes of pyrimidine synthesis are what? Ribonucleotide reductase Thymidylate synthetase Dihydrofolate reductase
What reduces NDPs to dNDP for DNA synthesis? What inhibits this enzyme? Ribonucleotide reductase which is inhibited by hydroxyurea
What methylates dUMP to dTMP, but requires Tetrahydrofolate (THF)? What inhibits it? Thymidylate synthetase inhibited by 5FU
What converts dihydrofolate to THF for the methylation reaction of thymydylate synthetase? Inhibited by? dihydrofolate which is inhibited by Methotrexate
What drugs can arrest the growth of rapidly growing cells? How? 5FU (5-flourouracil) and methotraxate block synthesis of dTMP
What is the most important enzyme in purine synthesis (de novo) PRPP amidotransferase catalyses the first, rate-limiting reaction
What drug can be prescribed to help a gout or hyperuracemia patient? Why? Allopurinol inhibits xanthine oxidase
What drug helps cancer patients by inhibiting PRPP amidotransferase? 6-mercaptopurine nucleotide
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
IF you have an Adenosine deaminase deficiency what condition results? How is it acquired? autosomal recessive condition that causes SCID - severe combined immunodeficiency
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
Gout can be caused by deficiency in two enzymes we studied. What are they? Glucose-6-P phosphatase = Von Gierke HGPRT
How does allopurinol react? non-competitive inhibitor of xanthine oxidase
Created by: El Diablo