Biochem- Nucleotide Metabolism
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96 terms
Terms | Definitions |
|---|---|
 What are nucleotides composed of? | Nitrogenous base Pentose monosaccharide 1, 2, or 3 phosphates |
| What is the base in inosine monophosphate? | Hypoxanthine |
| What is IMP used for? | Intermediate in purine synthesis and degradation |
| Where is Xanthine found? | Xanthosine MP |
| What is Xanthosine MP used for? | Intermediate in purine synthesis and degradation |
| Where are unusual bases found? | tRNA viral DNA |
| How are unusual bases formed? | Methyl derivatives of normal bases |
| What is a nucleoside? | Nucleotide without phosphates |
| What are the 2 pathways of purine nucleotide synthesis? | De novo Salvage |
| How is De novo purine synthesis done? | Creating ring by adding C and N to ribose-5-phosphate |
| What is ribose-5-phosphate synthesized by? | HMP pathway |
| Where is purine de novo synthesis performed? | Cytoplasm |
| What donates N and C to purine? | CO2 Glycine Asparate N-Formyl-THF Glutamine |
| What is PRPP formed from? | Ribose-5-phosphate |
| What produces ATP before purine synthesis occurs? | Ribose phosphate pyrophosphokinase |
| What is the first step (RLS) of de novo purine synthesis? | PRPP to 5'-phosphoribosylamine |
| What catalyses the RLS of de novo purine synthesis? | Glutamine:phosphoribosyl pyrophosphate amidotransferase |
| What is the RLS of purine de novo synthesis controlled by? | Glutamine concentration PRPP concentration |
| What inhibits the RLS of purine de novo synthesis? | AMP GMP IMP |
| What does purine de Novo synthesis require? | 4 ATP |
| What is the ultimate product of purine de novo synthesis? | Inosine 5'-monophosphate |
| What do sulfonamides and folate analogs inhibit in purine de novo synthesis? | Formyltransferase |
| What do sulfonamides inhibit in folate synthesis? | Dihydropteroate synthetase |
| What does methotrexate inhibit in folate metabolism? | Dihydrofolate reductase |
| What inhibits THF synthesis in proks? | Trimethoprim |
| What are 2 folate analogs used in leukemia treatment? | Methotrexate Aminopterin |
| How do cancer cells become resistant to MTX? | Increased dihydrofolate reductase synthesis |
| What does the synthesis of AMP from IMP require? what enzyme? | GTP (adeylosuccinate synthetase) |
| What does the synthesis of GMP from IMP require? What enzyme? | ATP (GMP synthetase) |
| What are the NMPs converted to? | NDP NTP |
| What enzyme converts NMPs to NDP and NTP? | Nucleoside monophosphate kinases Nucleoside diphosphate kinases |
| What does Mycophenolic acid inhibit? | IMP dehydrogenase |
| How does Mycophenolate act? | Reversible uncompetitive inhibitor Deprives B and T cells from nucleic acids |
| What is mycophenolate used for? | Graft rejection |
| What enzymes does purine salvage require? | HGPRT Adenine phosphoribosyltransferase |
| What is deficient in Lesch-Nyhan Syndrome? | HGPRT |
| What is seen in Lesch-Nyhan Syndrome? | Excess uric acid Self-mutilation Involuntary movements Mental retardation Gout Orange crystals in baby diapers Increased de novo purine synthesis |
| How is Lesch-Nyhan Syndrome transmitted? | X-linked |
| What are hypozanthine an guanine degraded to? | Uric acid |
| What happens to digested pyrimadines? | Absorbed in intestine |
| What nucleic sugars are absorbed? | Ribose Deoxyribose |
| What is ADA? | Adenosine deaminase |
| What does ADA do? | Converts Adenosine to Inosine |
| What happens in ADA deficiency? | SCIDS |
| Why is adenine converted to inosine? | Inosine and guanine are better for purine nucleoside phosphorylase |
| What is seen biochemically in SCIDS? | DNA not synthesized in B and T cells due to accumulation of dATP |
| What reactions does PNP catalyse? | Inosine to hypoxanthine Guanine to guanosine |
| what is gout treated with? | Inhibitors of xanthine oxidase (allopurinol) |
| What reaction does xanthine oxidase catalyse? | Xanthine to uric acid |
| What does PNP deficiency cause? | Impaired T cell function |
| What is seen in PNP deficiency? | Decreased uric acid production Increased purine nucleosides and tides |
| What 3 deficiencies cause gout? | GALT Aldolase B G6Phosphatase |
| What is seen in gout? | Hyperuricemia Acute arthritic joint inflammation |
| What causes Acute arthritic joint inflammation in gout? | Deposition of uric acid crystals |
| What causes primary gout? | Genetic |
| How can secondary gout occur? | Leukemia Polycythemia HGPRT deficiency |
| How is gout diagnosed? | Presence of monosodium urate crystals in synovial fluid |
| What are treatment for gout? | Colchicine Allopurinol |
| What does colchicine do? | microtubule inhibitor |
| What does allopurinol do? | Non-competitive inhibition of xanthine oxidase |
| What is excreted in gout treatments instead of uric acid? | Hypoxanthine Xanthine |
| What is the RLE of pyrimidine synthesis? | Carbamoyl phosphate synthetase II (CPS II) |
| What is the action of CPS2 | Glutamine+CO2 to Carbamoyl phosphate |
| What provides C and N for pyrimidine synthesis? | Glutamine Aspartate CO2 |
| What inhibits CPS II? | UTP |
| What activates CPS II? | ATP PRPP |
| WHere is CPS I used? | Urea synthesis |
| What do CPS I and II use as source of N? | I - Free amonia II - Glutamine |
| Where is CPS I and II? | I - Liver mitochondira II - Cytosol of all cells |
| What activates CPS I? | N-acetylglutamate |
| Does N-acetylglutamate activate CPS I? | No |
| Is CPS I affected by UTP/UDP? | No |
| What is elevated in orotic aciduria? | Orotate |
| What is deficient in Orotic aciduria? | Orotate phosphoribosyltransferase OMP decarboxylase |
| What is seen in orotic aciduria? | Abnormal growth Megaloblastic anemia Excretion of orotate in urine |
| How can acquired orotic aciduria arise? | Cancer treatment with pyrimidine analog |
| How is genetic orotic aciduria treated? | Dietary Uridine |
| How is CTP synthesized from UTP? | CTP synthase |
| How is UTP formed? | UMP to UDP to UTP Nucleoside monophosphate kinase Nucleoside diphosphate kinase |
| What is the nitrogen donor for UTP to CTP? | Glutamine |
| What catalyses ribonucleotide reductions? | Ribonucleotide diphosphate reductase |
| What inhibits Ribonucleotide diphosphate reductase? | dATP Hydroxyurea |
| What activates Ribonucleotide diphosphate reductase? | ATP |
| What sites does Ribonucleotide diphosphate reductase have? | 2 Substrate specific sites 2 Activity sites |
| How many active sites does Ribonucleotide diphosphate reductase have? | 1 |
| How many activity sites and substrate specificity sites does Ribonucleotide diphosphate reductase have? | 2 and 2 |
| What produces dTMP from dUMP? | Thymidylate synthase |
| What does thymidylate synthase require? | THF |
| What inhibits Thymidylate synthase? | Indirectly by MTX Directly by 5-fluoruoacil |
| What kind of analog is 5-fluoruoacil? | Uracil analog |
| What are the thymidine analogs? | Bromodeoxyuridine Trifluorothymidine |
| What boosts 5-fluoruoacil effectiveness? | Thymidine |
| What does 5-fluoruoacil normally do? | Converted to dFUMP Inhibits thymidilate synthase |
| What does 5-fluoruoacil do in cancer cells? | Incorporated in to Cancer cells |
| Is inhibition of thymidilate synthase selective? | No |
| How are pyrimidines salvaged? | Pyrimidine phosphoribosyltransferase |
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