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Nucleotides; DNA
| Question | Answer |
|---|---|
| what number carbon of the ribose sugar is missing the oxygen in a deoxy nucleotide | the number 2 carbon |
| what's the origin of most nucleobases | our diet or from being recycled |
| what are the major intermediates in the formation of purines | IMP (inosine-5'-monophosphate), and PRPP |
| how is the purine ring built | IMP is built in several steps after the first nitrogen is attached to PRPP. then IMP is converted into AMP or GMP |
| what coenzyme is involved in purine synthesis | folate |
| how is IMP converted to AMP | IMP is condensed with aspartate in the presence of adenylosuccinate synthetase. It uses one GTP. The product is acted on by adenylosuccinate lyase which cleaves off fumarate and leaves AMP. |
| how is IMP converted to GMP | IMP is condensed with water in the presence of IMP dehydrogenase to form Xanthosine monophosphate. This is acted on by GMP synthetase in the presence of glutamine and one ATP to produce GMP and glutamate |
| what activates PRPP synthesis and what inhibits it | PRPP synthesis is activated by free phosphate and inhibited by purine nucleoside di- and tri- phosphates |
| what inhibits conversion of IMP to adenine nucleotides | ATP, ADP, and AMP |
| how do sulfonamides inhibit growth of bacteria | sulfonamides inhibit bacterial synthesis of folic acid which is needed in purine synthesis. |
| how does methotrexate work to control cancer | methotrexate is a structural analog of folic acid and interferes with purine synthesis |
| what enzyme is needed in hypoxanthine and guanine salvage reactions | HGPRT |
| what precursor is needed to salvage any purine the appropriate phosphoribosyltransferase | PRPP |
| complete the following : hypoxanthine + PRPP ==via HGPRT=> | IMP + PPi |
| what disease is caused by deficiency of HGPRT | Lesch Nyhan disease |
| what are symptoms of Lesch Nyhan disease | high uric acid conc., neurologic issues like self mutilation, mental retardation, increased de novo synthesis |
| in pyrimidine synthesis where do the carbon and nitrogen come from | carbamoyl phosphate and aspartate |
| what enzyme is involved in the committed step in pyrimidine synthesis | ATCase |
| name the intermediates in the formation of UMP from dihydroorotate | orotate==> OMP ==> uridine monophosphate (UMP) |
| how is UTP made from UMP | by a kinase |
| how is CTP made | CTP is produced by the amination of UTP by CTP synthetase |
| what enzymes does CTP inhibit | ATCase and CTP synthetase |
| what enzyme does UMP inhibit | carbamoylphosphate synthetase |
| how are nucleic acids degraded | by nucleases to oligonucleotides |
| what acts on oligonucleotides | phospho-diesterases and yields nucleotides |
| what do nucleotidases do | they remove phosphate from nucleotide and yield nucleoside |
| what are the intermediates in the breakdown of GMP | guanine ==> xanthine |
| what are the intermediates in the breakdown of AMP | AMP==> hypoxanthine (via ADA) ==> xanthine (via xanthine oxidase) |
| how is uric acid produced | xanthine oxidase acts on xanthine to produce uric acid which is excreted in the urine |
| what are the symptoms of ADA (adenosine deaminase) deficiency | severe immunodeficiency (affects T and B cells); extremely high buildup of dATP which inhibits ribonucleotide reductase and thus depresses DNA synthesis |
| what causes gout | high uric acid in the blood |
| what are the two types of gout and their causes | one is caused by genetic defect which causes overproduction of uric acid; the other can be caused by other diseases such as cancer, HGPRT deficiency, renal insufficiency |
| how does allopurinol work | it inhibits xanthine oxidase which blocks uric acid synthesis. also causes accumulation of hypoxanthine and xanthine which are more soluble than uric acid |
| what are the two ways pyrimidines can be degraded | pyrimidine ring can be opened and degraded to soluble products e.g. beta alanine that can serve as a precursor to acetyl CoA. Also pyrimidines can be salvaged and converted into other nucleotides using PRPP as soure of ribose-P |
| the drugs methotrexate, aminopterin, and trimethoprim interfere with which reduction process | reduction of DHF(dihyrofolate) to THF |
| in the conversion of dUMP to dTMP, which enzyme is FdUMP blocking | thymidylate synthase |
| on what end of nucleotide does polymerization take place | on the 3' end |
| what other forces contribute to DNA helix stability other than hydrogen bonds | hydrophobic interactions among the bases; base stacking results in weak van der Waals attractions; electrostatic interactions with Mg2+ and histones |
| what can happen to DNA as a result of ionizing radiation | strand breaking and base modifications esp. thymine dimers |
| what two nucleotides are especially susceptible to alkylation | adenine and guanine |
| what impact does nitrous acid have on bases | it deaminates bases |
| what impact do polyaromatic hydrocarbons have on DNA | they are mutagenic and prevent base pairing |
| what are intercalating agents and what do they do to DNA | they can insert between base pairs and cause frame-shift mutation |
| how does the Z form of DNA differ from the B form | Z form is left handed helix |
| what types of enzymes control DNA supercoiling | topoisomerases |
| what does type I topoisomerase do | it creates transient single-stranded breaks allowing the DNA to uncoil |
| what does type II topoisomerase do | it creates transient double stranded breaks |
| what is prokaryotic type II topoisomerase called | DNA gyrase |
| how does the antibiotic cipro work | it inhibits DNA gyrase but not eukaryotic topoisomerase II |
| how do cancer drugs doxorubicin and etoposide work | they inhibit eukaryotic topo II and increase number of ds DNA breaks |
| how do polyamines help packing of DNA | they bind to DNA and help neutralize DNA's -ve charge for denser packing |
| what is the role of histones | they regulate access to DNA of transcription factors |
| what are telomeres | GGGT repeats at the end of DNA that postpone loss of coding on replication |
| in recombinant genetics, what is transformation | naked DNA breaches the cell wall and is incorporated into the genome |
| what is transduction | occurs when a bacteriophage inadvertently carries DNA to a recipient cell |