What are nucleotides composed of?
1, 2, or 3 phosphates
What is the base in inosine monophosphate?
What is IMP used for?
Intermediate in purine synthesis and degradation
Where is Xanthine found?
What is Xanthosine MP used for?
Intermediate in purine synthesis and degradation
Where are unusual bases found?
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?
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?
Where is purine de novo synthesis performed?
What donates N and C to purine?
What is PRPP formed from?
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?
What inhibits the RLS of purine de novo synthesis?
What does purine de Novo synthesis require?
What is the ultimate product of purine de novo synthesis?
What do sulfonamides and folate analogs inhibit in purine de novo synthesis?
What do sulfonamides inhibit in folate synthesis?
What does methotrexate inhibit in folate metabolism?
What inhibits THF synthesis in proks?
What are 2 folate analogs used in leukemia treatment?
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?
What enzyme converts NMPs to NDP and NTP?
Nucleoside monophosphate kinases
Nucleoside diphosphate kinases
What does Mycophenolic acid inhibit?
How does Mycophenolate act?
Reversible uncompetitive inhibitor
Deprives B and T cells from nucleic acids
What is mycophenolate used for?
What enzymes does purine salvage require?
What is deficient in Lesch-Nyhan Syndrome?
What is seen in Lesch-Nyhan Syndrome?
Excess uric acid
Orange crystals in baby diapers
Increased de novo purine synthesis
How is Lesch-Nyhan Syndrome transmitted?
What are hypozanthine an guanine degraded to?
What happens to digested pyrimadines?
Absorbed in intestine
What nucleic sugars are absorbed?
What is ADA?
What does ADA do?
Converts Adenosine to Inosine
What happens in ADA deficiency?
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?
What is seen in gout?
Acute arthritic joint inflammation
What causes Acute arthritic joint inflammation in gout?
Deposition of uric acid crystals
What causes primary gout?
How can secondary gout occur?
How is gout diagnosed?
Presence of monosodium urate crystals in synovial fluid
What are treatment for gout?
What does colchicine do?
What does allopurinol do?
Non-competitive inhibition of xanthine oxidase
What is excreted in gout treatments instead of uric acid?
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?
What inhibits CPS II?
What activates CPS II?
WHere is CPS I used?
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?
Does N-acetylglutamate activate CPS I?
Is CPS I affected by UTP/UDP?
What is elevated in orotic aciduria?
What is deficient in Orotic aciduria?
What is seen in orotic aciduria?
Excretion of orotate in urine
How can acquired orotic aciduria arise?
Cancer treatment with pyrimidine analog
How is genetic orotic aciduria treated?
How is CTP synthesized from UTP?
How is UTP formed?
UMP to UDP to UTP
Nucleoside monophosphate kinase
Nucleoside diphosphate kinase
What is the nitrogen donor for UTP to CTP?
What catalyses ribonucleotide reductions?
Ribonucleotide diphosphate reductase
What inhibits Ribonucleotide diphosphate reductase?
What activates Ribonucleotide diphosphate reductase?
What sites does Ribonucleotide diphosphate reductase have?
2 Substrate specific sites
2 Activity sites
How many active sites does Ribonucleotide diphosphate reductase have?
How many activity sites and substrate specificity sites does Ribonucleotide diphosphate reductase have?
2 and 2
What produces dTMP from dUMP?
What does thymidylate synthase require?
What inhibits Thymidylate synthase?
Indirectly by MTX
Directly by 5-fluoruoacil
What kind of analog is 5-fluoruoacil?
What are the thymidine analogs?
What boosts 5-fluoruoacil effectiveness?
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?
How are pyrimidines salvaged?