Lect22 - Lecture 22 Nucleotide Biosynthesis 1 Important...

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1 Lecture 22 Nucleotide Biosynthesis
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2 Important concepts 1. Understand the synthesis of pyrimidine Memorize the donor of each atom Understand synthesis of PRPP Understand the advantages of substrate channeling 2. Understand the synthesis of purine Memorize the donor of each atom
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3 Roles of Nucleotides • Precursors to nucleic acids (genetic material and ribonucleic enzymes) • Currency in energy metabolism (e,g., ATP, GTP) • Carriers of activated metabolites for biosynthesis (e.g., UDP-glucose) • Structural parts of coenzymes (e.g., NAD, CoA) • Metabolic regulators and signal molecules (e.g., cAMP)
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4 nucleotide nucleoside
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5
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6 Purines Pyrimidines 6
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Nucleotides can be synthesized by salvage or de novo pathways 7 pre-formed Synthesis of pyrimidine ring first, then add to ribose Purine bases are assembled on ribose phosphate
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8 Pyrimidines: de novo synthesis •From bicarbonate, aspartate and ammonia •Ammonia usually from hydrolysis of the side chain of glutamine (N donor) •Synthesis of pyrimidine ring first, then add to ribose
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9 •Catalyzed by an ATP-grasp domain in carbamoyl phosphate synthetase (same as the first step of Urea cycle) •Consume 2 ATPs Pyrimidines: de novo synthesis
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10 Reminder: Urea Cycle
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11 Advantages of channeling: •No intermediate loss by diffusion •Protect labile intermediates from hydrolysis Carbamoyl phosphate synthetase: Intermediates move between active sites by channeling 45Å 35Å
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12 Pyrimidines: de novo synthesis Aspartate transcarbamoylase Finish the pyrimidine ring
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13 Very Important Molecule 1 5
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14 Ribose Phosphate Pyrophosphokinase:
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This note was uploaded on 03/04/2012 for the course CHEM 114B taught by Professor Wang during the Spring '09 term at UCSD.

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Lect22 - Lecture 22 Nucleotide Biosynthesis 1 Important...

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