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37 Cards in this Set
- Front
- Back
What is the salvage path used for?
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Reutilization of bases, sugars and nucleosides
Overlaps with degradation more varied between species and kingdoms |
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How do enz work in the salvage path?
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Can work fwds or bcwds
-> use bases to make nucleotides --> degrade nuc to make bases (depends on metabolic need of the cell) |
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What enz is req'd to go from nucleoside to base?
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Nucleoside phophorylase
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Wht enz is req'd to go from a nucleoside to a nucleotide?
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Nucleoside kinase
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What happens when the cell sees a U in DNA
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Thinks a C got deaminated
->specific repair system for spotting U bases => Uracil-DNA Glycosylase leaves a ribose without a base, then DNA pol comes in and fills the gap |
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What are the enzymes of the salvage path?
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Phosphoribosyl transferase: base-> ribonucleotide
Nucleoside Phosphorylase: base <=> nucleotide Nucleoside kinase: nucleoside-->nucleotide Nucleoside transglycosylase: base <=> deoxynucleoside Deaminases: interconversion of bases Nucleoside monoP kinase: rNMP-->rNDP, dNMP-->dNDP Nucleoside diP kinase: rNDP--> rNTP, dNDP-->dNTP |
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Which of these enz have already been seen in the pyrimidine de novo path?
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Phosphoribosyl transferase
(took orotic acid and added PRPP to make orotate, a nucleotide) |
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Which of these enz have been used in the de novo path?
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nucleoside diP kinase
nucleoside monoP kinase |
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What is needed to convert a base to a ribonucleotide?
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Hypoxanthine/guanine phosphoribosyl transferase (HGPRT)
Hypoxanthine + PRPP --> Inosinate (IMP) + PPi Guanine + PRPP --> Guanylate (GMP) + PPi -Use other enz for A and U (get a nucleotide from a base, up 2 lvls in the house) |
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What is Lesch-Nyhan disease?
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Genetic disease
Loss of HGPRT activity Symptoms: Gout and mental retardation |
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When can you get a genetic disease?
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Only get a genetic disease if intermediate in the phenotype, if the gene is essential
-->otherwise its probly embryonic lethal |
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How are nucleosides formed? (2)
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1)Nucleoside phosphorylase: sugar + base <=> nucleoside
ribose-1-P has P in α position, when base added, switch to β anomer 2) Nucleoside transglycosylase: swaps bases in 1 step, has a specificity to avoid making thymine ribonucleosides. Using nucleoside Phosphorylase 2x to switch bases deoxyadenosine <=> deoxyribose-1-P <=> Thymidine |
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What happens when there are an excess of bases?
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Start deaminating
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What does mutase do?
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Switches P form the 5' to the 1' position
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What is created as purines are degraded?
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Nucleosides
Bases, xanthine Uri acid |
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How is AMP degraded?
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Remove amino group and makes AMP into IMP and then remove the P to get inosine
or remove P with nucleotidase, then deaminate to get inosine |
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What happens once you get inosine?
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use purine nucleoside phophorylase (PNP) to make inosine --> hypoxanthine
-Use xanthie oxidase to get xanthine |
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How are XMP and GMP degraded?
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XMP:Use nucleotidase (xanthosine) and then PNP to get Xanthine
GMP: Use nucleotidase (Guanosine) then PNP to get guanine, then use guanine oxidase to get to Xanthine |
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What happens once you get xanthine?
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Use xanthine oxidase to make Uric Acid
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What happens if a person doesn't have adenosine deaminase?
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Can't convert AMP--> IMP or A-> IGet genetic disease: SCID
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What happens happens if xanthine oxidase is inhibited?
When is this used as a treatment? |
Block degradation of purines
Don't add O2 to Hypoxanthine to get xanthine Used to treat gout (too much uric acid: gout) |
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What is gout?
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Deposition of uric acid in joints
-> painful, prevalent in males (middle aged) ->thought to be due to excess meat -> more likely due to kidney dysfct (have kidney problems, more likely to have gout because you can't secrete uric acid efficiently) -symptomatic of metabolic imbalance: too much de novo purine synthesis (high PRPP lvls) |
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How is gout associated with Lesch-Nyhan disease?
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Can't reuse guanine orhypoxanthine, so all the G and hypoxanthines have to be degraded .: kids with the HGPRT disease have gout at the same time, all G has to be degraded, can't be reused, get too much uric acid -> gout
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What is the final degradtion product of purines?
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Uric acid
->elimination of N by birds (conservation of water) -> less soluble at low pH therefore it wil ppt out |
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What happens in pyrimidine degradation?
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->nucleosides
->bases ->uracil (thymine) |
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What genetic disease is associated with regulation of CPSII?
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Orotic aciduria
Treatment: block de novo synthesis of pyrimidines Supplement diet with uridnie: .: will make lots of salvage path and stop doing de novo pyr syn |
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What genetic disease it ass't with the inhibitors of xanthine oxidase?
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1) Lesch-Nyhan (HGPRT)
Treatment: block purine salvage path, use allopurine (inhibits uric acid production) to block xanthine oxidase 2) SCID: problem with adenosine deaminase or purine nucleoside phosphorylase treatment: gene therapy? (not very effective) |
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What are the inhibitors of purine sythesis (3)?
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Azoserine
6Diazo-5-oxo-L-norleucine (DON) 6-Mercaptopurine (thioIMP): can block the salvage path -> look like glutamine, block all the steps where we use amino gp rom the side chain of glutamine |
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What are the inhibitors of pyrimidine synthesis? (2)
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PALA: inhibits aspartate transcarbamylase, looks like aspartic acid + carbamoyl P
6-Azauridine (azaUMP):inhibits orotidylate decarboxylase (can't decarboxylate orotidylate to uracil) |
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What are the inhibitors of folate synthesis? (3)
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Sulfonamides: inhibit folate biosynthesis, works well vs bacteria,block THF synthesis
Amethopterin (methotrexate): block folate (DHF) reductase, can't do DHF--> THF (good vs bacteria) Aminopterin: same as above |
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What are inhibitors of deoxyribonuceotide synthesis? (2)
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Hydroxyurea: inhibits ribonucleotide reductase (RR), quenches tyr free radical
dFUMP (5-flurouracil deoxynucleoside): inhibits thymidylate synthetase, can't make dTMP from dUMP |
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What is the inhibitor of DNA, RNA synthesis?
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AZT/dideoxycytidine: inhibits polymerase (DNA), missing O on 3' position, block chain elongation when incorporated into DNA and RNA
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What does AZT have in the 3' position instead of an O? Dideoxycytidine?
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AZT: N3
Dideoxycytidine: H |
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What are RR inhibitors?
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Hydroxyurea: quench tyrradical
Peptide inhibitors of dimerization (of viral RR) |
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What does Azauridine do?
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Inhibits step #6 of pyrimidine de novo path
Has an extra N in pyrimidine ring Leads to orotic aciduria |
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What does thioIMP do?
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has an S in place of an O in hypoxanthine (IMP)
thioIMP accumulates in cells-> represses de novo purines (IMP--> GMP and IMP-->AMP) -Antitumour drug used for leukemia |
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What do anaogues of glutamine do?
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Inhibit aminotransferase rxns
too toxic for clinical use Azaserine: has extra CHN2 and O DON: has extra CHN2 |