Lecture_24_4-27-10-PDF_42015

Lecture_24_4-27-10-PDF_42015 - Review Pyrimidine...

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Pyrimidine biosynthesis utilizes precursors Review
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Purine biosynthesis Purine biosynthesis utilizes precursors Review
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The linkage of RNA to a ‘DNA world’ raises the possibility that might be important in this process. RNA to a ‘DNA world’ Review
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The mechanism of ribonucleotide reductase (Class I) Step 4 Step 4. The radical cation intermediate is reduced by the enzyme's redox-active sulfhydryl pair. This oxidized disulfide must become reduced so RNR can regain its activity. ( the book states this incorrectly ) Lec 23 Review
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Drugs designed to inhibit the reproduction of cancer cells Review
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Drugs designed to inhibit the reproduction of cancer cells 1. Rapidly growing cancer cells require steady supply of dTMP for DNA synthesis . 2. Most normal mammalian cells require little dTMP (exceptions: bone marrow, immune system, intestinal mucosa, hair follicles) Cancer treatment which impairs dTMP synthesis. Thymidylate synthase is inhibited by methotrexate and other anticancer drugs. Review Possible side effects?
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4. Nucleotide Degradation A. Catabolism of Purines B. Fate of Uric Acid C. Catabolism of Pyrimidines Nucleotide metabolism (Lec 24) Chapter 23
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1. Nucleosidase : Nucleoside + H 2 O base + ribose 2. Nucleoside phosphorylase : Nucleoside + P i base + ribose-1-phosphate Two possible pathways The de novo pathways of nucleotide biosynthesis largely satisfy an organism’s need for nucleotides Nucleotide Degradation (overview)
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ribose-1-phosphate ribose-5-phosphate PRPP 1. Phosphopentomutase 2. Ribose phosphate pyrophosphokinase 1 2 Sugars are further metabolized
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ribose-1-phosphate ribose-5-phosphate Sugars are further metabolized 1. Phosphopentomutase
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ribose-1-phosphate ribose-5-phosphate PRPP 1 2 Lec-22
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Chapter 15
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Biosynthetic routes De novo (anew) and salvage pathways
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The major pathways of purine catabolism in animals
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Adenosine/deoxyadenosine are not degraded by animal’s purine nucleotide phosphorylase ( PNP ). Rather, adenine nucleoside/nucleotide are deaminated by adenosine deaminase ( ADA ) and adenylate ( AMP ) deaminase to their corresponding inosine derivatives. No PNP
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Guanine nucleotides are hydrolyzed to the nucleoside guanosine which undergoes phosphorolysis to guanine and ribose 1-P .
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Both adenine and guanine nucleotides converge at the common intermediate xanthine . Hypoxanthine , representing the original adenine , is oxidized to xanthine by the enzyme xanthine oxidase. Guanine is deaminated, with the amino group released as ammonia, to xanthine . Xanthine , like hypoxanthine, is oxidized by oxygen and xanthine oxidase with the production of hydrogen peroxide. The hydrogen peroxide is degraded by catalase. Catabolism of Purines
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1. Both adenine and guanine nucleotides converge at the common intermediate xanthine .
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This note was uploaded on 09/15/2010 for the course BCHS 3305 taught by Professor Fujita during the Spring '10 term at University of Houston.

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Lecture_24_4-27-10-PDF_42015 - Review Pyrimidine...

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