Lecture 3 Nucleotide Biosynthesis

Lecture 3 Nucleotide Biosynthesis - Chapter25...

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Chapter 25 Nucleotide Biosynthesis  
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Why study nucleotides and their metabolism? 1. They are basic units of genetic information – “building block of  DNA and RNA” 2.  Activated  intermediates are involved in many biosynthetic  reactions  (UDP-glucose, CDP-diacylglycerol) 3. ATP is a nucleotide and is a major form of energy storage and  exchange in the cell 4. Adenine nucleotides as coenzymes (FAD, NAD, Coenzyme A) 5. Nucleotides are essential components of second messengers  (cyclic AMP, cyclic GMP…) 6. Implication in diseases & treatment
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+sugar +phosphate (always deoxy-)
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Nucleotides can be synthesized by salvage or de novo pathways (1) (2) (using a pool) (PRPP: 5-phosphoribosyl-1-pyrophosphate)
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De novo pathway for pyrimidine nucleotide synthesis (activated) c o n v e r t d u i
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De novo synthesis of pyrimidine ring 1.bicarbonate is  activated  by phosphorylation 2.ammonia reacts with carboxyphosphate 3.formation of carbamoyl phosphate by phosphorylation “activation” “exchange” <2ATP, NH (ammonium ion from glutamine)> Carbamoyl phosphate synthetase
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4.  formation of carbamoyl aspartate by aspartate  transcarbamoylase (ATCase) : limiting step 5. formation of orotate ATCase “close the structure” “oxidation”
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6. formation of orotidylate and uridylate (UMP) “hydrolysis” “decarboxylate” Orotidylate decarboxylase
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Formation of NDPs and NTPs from NMPs 1. NMP + ATP   NDP + ADP  (N = any nucleotide)     catalyzed by nucleotide specific  enzymes     e.g.:  UMP kinase UMP + ATP   UDP + ADP 2. NTPs are formed by nucleoside diphosphate kinase (broad  specificity ) XDP + YTP   XTP + YDP
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Synthesis of CTP (cytidylate synthase) UTP is converted to CTP by replacement  of a carbonyl group  by an amino group.
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Lecture 3 Nucleotide Biosynthesis - Chapter25...

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