Lecture 22 - 022811

Lecture 22 - 022811 - Lecture 22 Nucleotide Biosynthesis 1...

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1 Lecture 22 Nucleotide Biosynthesis
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2 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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3 nucleotide nucleoside
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4
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5 Purines Pyrimidines 5
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6
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Nucleotides can be synthesized by salvage or de novo pathways 7
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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 Urea Cycle
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11 Carbamoyl phosphate synthetase (CPS) Generate ammonia •Two ATP-grasp domains: One for bicarbonate=>carbamic acid One for carbamic acid =>carbamoyl phosphate •ATP-grasp domain catalyzes the formation of C-N bonds through acyl- phosophate intermediate •Two ATP-grasp domains are formed by gene duplication and then diverge
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12 •Side chain of glutamine hydrolyzed to generate ammonia •Active sites are separated •Advantages of channeling: •No intermediate loss by diffusion •Protect labile intermediates from hydrolysis Intermediates move between active sites by channeling 45Å 35Å
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13 Pyrimidines: de novo synthesis Aspartate transcarbamoylase Finish the pyrimidine ring
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14 Very Important Molecule 1 5
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This note was uploaded on 08/15/2011 for the course CHEM 114B taught by Professor Wang during the Spring '09 term at UCSD.

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Lecture 22 - 022811 - Lecture 22 Nucleotide Biosynthesis 1...

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