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Block 6-purine pyri
Block 6 purine and pyrimidine metabolism
| Question | Answer |
|---|---|
| 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
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