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27 Cards in this Set
- Front
- Back
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How is pyrimidine synthesis different than purine in terms of assembly on or onto PRPP?
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- in purines the ring is made on PRPP
- in pyrimidines the skeleton is made first then attached to PRPP |
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The major regulatory step of pyrimidine synthesis in eukaryotes is __________. The next level of regulation is at ________.
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- the formation of carbomyl phosphate by CPS II
- OMP-decarboxylase |
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What is carbamoyl phosphate made up of for pyrimidine synthesis?
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- 2ATP + bicarb + NH3 from glutamine
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What are the 3 steps after you make carbamoyl phsophate in pyrimidine synthesis?
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1) carbamoyl phosphate + aspartate (via aspartate transcarbamoylase) --> N-carbamoylaspartate
2) N-carbamoylaspartate via dihydroorotase --> dihydroorotate 3) dihydroorotate via dihydroorotate dehyrdrogenase --> orotate |
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Once orotate is formed what happens?
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1) orotate phosphoribosyl transferase adds PRPP --> orotidylate
2) orotidylate decarboxylase turns it into UMP |
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Once UMP is formed how do you get it to UTP?
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- uridylate kinase turns UMP into UDP
- nucleoside diphosphate kinase turns UDP into UTP |
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UTP is converted to CTP via ________ which adds what?
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- CTP synthase
- adds an amine group via glutamine --> glutamate |
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What is the pyrimidine ring made out of?
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- glutamine amide
- aspartate - bicarb |
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The first three enzymes in the pyrimidine synthesis pathway (_____, ____ & ______) are all domains of the same polypeptide chain.
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CPS II, aspartate transcarbamoylase and dihydroorotase
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What are the 2 steps in pyrimidine salvage?
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- reversible conversion of bases to nucleosides catalyzed by phosphorylase
- pyrimidine --> pyrimidine-ribose via phosphorylase using ribose-1-phosphate --> ribose - then phosphorylate the pyrimidine-ribose to get pyrimidine-ribose-phosphate |
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Why do the end products of pyrimidine catabolism not cause gout?
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- the end products are soluble
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during pyrimidine catabolism: nucleotides are converted to nucleosides by _________, then what happens to cytidine? Then what happens to the end products?
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- phosphatases
- cytidine is deaminated via cytosine deaminase to uridine - uridine & thymidine (nucleosides) are converted to free bases by pyrimidine nucleoside phosphorylase |
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The end breakdown product of uracil is _______, precursor of ______. Thymine is ________, precursor of ________. Which ones is measured in chemotherapy?
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- beta-alanine
- acetyl CoA - beta-aminoiobutyrate - succinyl CoA - beta-aminoisobutyrate is measured to look at cell breakdown/turnover |
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what level are riboses turned into deoxyriboses? (NTP? NDP? NMP?) What enzyme does this?
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- diphosphates
- ribonucleotide reductase |
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How does ribonucleotide reductase work?
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- ribose --> deoxyribose via SH groups on ribonucleotide reductase
- S-S bond how regenerated by more SH groups on thioredoxin - thioredoxin S-S bonds now regenerated via SH groups on thioredoxin reductase - thioredoxin reductase S-S bond now regenerated via FADH - which turns into FAD & gets regenerated by NADPH |
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hydroxyurea
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- inhibits ribonucleotide reductase via stopping the tyrosyl free radicals involved in making the dNTPs
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What is special about the formation of dTMP?
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- UDP --> dUDP --> dUMP --> dTMP
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What converts dUTP --> dUMP?
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- dUTP diphosphohydrolase
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How is dTMP synthesized from dUMP?
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- dUMP --> dTMP via thymidylate synthase (one methyl donation) via 5 10 THF --> DHF
- DHF is regenerated to THF by dihydrofolate reductase - THF is turned back into N5 N10 THF via serine hydroxymethyl tranferase (serine --> glycine) |
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FdUMP
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- blocks dUMP --> dTMP via blocking thymidylate synthase
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mehotrexate, aminopterin, trimethoprim: what do they do? Who does methotrexase resemble? what synthesis does it inhibit?
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- block regeneration of THF from DHF by blocking dihyrofolate reductase - used for tumor treatment
- methotrexate resembles DHF that's why it can bind & compete with DHF reductase --> inhibits synthesis of dTMP |
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end products of pyrimidine synthesis (UTP, CTP) feed back on _______ to inhibit it. ___ & ____ activate this enzyme.
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- CPS II
- ATP, PRPP |
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PRPP activates what 2 enzymes in pyrimidine synthesis?
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- CPS II
- orotate phosphoribosyl tranfserae |
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UMP feeds back on _____ to inhibit it.
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- OMP decarboxylase
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orotic aciduria & how do you treat
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- caused by absence of either or both of OPRT or orotidylate decarboxylase
- high levels of orotic acid secreted - anemia & failure to grow - give them UMP b/c this bypasses the defects |
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____ is the major allosteric inhibitor of ribonucleotide reductase, whereas ATP activates it. dGTP turns of ____ synthesis, but turns on ______.
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- dATP
- deoxysynthesis besides dATP |
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why can ADA deficiency cause SCID like symptoms?
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- large buildup of dATP b/c don't have adenosine deaminase (which works on both ribose & deoxyribose)
- this inhibits ribonucleotide reductase which can ultimately block DNA synthesis required for immune system |
