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23 Cards in this Set
- Front
- Back
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What are Antimetabolites?
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analogues of folate, purines, and pyrimidines taht inhibit enzymes involved in nucleotide synthisis
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What do inhibitors of folate metabolism accomplish?
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bacteria synthesize folate while amammalian cells can uptake dietary folate.
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what do the antimetablites of purine do?
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they block the de novo synthisis or conversion from salvage pathway
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what to the antimetabolites of ribonucleotides do?
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block synthisis of deoxyribonucleotides
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what to the antimetabolites that are incorporated into DNA do?
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block DNA synthesis
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what can use of antimetabolites treatments?
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antibacterial agents
antifungal agents antiparasitic agents antienoplastic agents (inhibit tumors) also used as immunosuppressants |
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how are the requirments of nucleotides met?
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dietary intake or de novo syntheis
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salvage pathways are a mojor source of nucleotides for?
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synthesis of DNA, RNA, and enzyme co-factors
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Ingested nucleotides are hydrolyzed in the gut yielding what?
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ribose-1-P and free bases
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If the nucleosides and or bases are not reutilized the purines and pyrimidines are degraged into what?
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purines into uric acid
pyrimidines into B-alanine and B-aminoisobutyrate, NH3 and CO2 |
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major site of purine synthesis?
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liver
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De novo synthesis
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step1:
phosphorylation of ribose 5-phosphate + ATP --> PRPP + AMP |
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What is the De Novo synthesis inhibited by?
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mecaptopurine metabolite
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what are the steps of 5-FU activation?
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FdUMP forms a coalent ternary complex iwth methyleneTHF and theymidylate synthase blocks dTMP formation, dominate mechanism of anti-metabolite
phosphorylation of loxuridine to FUTP can also occur, FUTP is incorporated into mRNA and blocks proper processing of the mRNA, minor mechanism Combination therapy with Leucovorin has proven more effective in treaving colon and rectal cancer dur to increased conc. of methyleneTHF |
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what inhibits ribonucleotide reductase? and how? used to treat what?
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hydroxyurea or hydroxycarbamide (hydrea)
scavenging a tyrosyl radical at the active center of the enzyme blocks reduction of th ribose to deoxyribose sickle cell anemia |
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What does T-IMP acomplish?
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inhibits eventual conversion of IMP to AMP and GMP
T-IMP is a feedback inhibitor of PRPP synthase (first enzyme in de novo purine synthesis) does not affect DNA synthesis directly |
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what drug blocks Xanthine Oxidase?
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allopurinol
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what is Pentostatin? why is it used?
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a nucleoside analog that inhibits adenosine deaminase stoping purine metabolism.
used for hairy cell leukemia. (high adenosine increases the metabolite S-adenosylmethionine which is toxic to lymphocytes.) |
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How do rogue metabilites halt DNA synthesis?
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rouge metabolites form triphosphorylated nucleotide analogs that become incororated into DNA leading to chain termination., disruption of secondary structure of DNA resulting in stand breakage.
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what is one rouge metabolite and how is it used.
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Thioguanine
once incorporated in DNA it interferes iwth transcription and DNA replication also decreases GMP synthesis. treat myelocytic leukemia |
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what does Fludarabine-5-Phosphate (fludara) do.
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inhibits DNA polymerase and ribonucleotide reductase to reduce nucleotide synthesis.
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what is Cladribine (Leustat)
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incorporation into DNA causes stand breaks
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what does fludara and leustat have in common?
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they are resistant to deamination by adenosine deaminase
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