Purine and Pyrimidine Biosynthesis PDF

Purine and Pyrimidine 1 Biosynthesis Dr. Mohamed Zahir  2 Outline ▪ Introduction ▪ What are Purine and Pyrimidine bases ▪ Molecular structure of Purine and pyrimidine bases ▪ Nucleosides and Nucleotides ▪ Synthesis of Purine nucleotides ▪...

Purine and Pyrimidine 1 Biosynthesis Dr. Mohamed Zahir  2 Outline ▪ Introduction ▪ What are Purine and Pyrimidine bases ▪ Molecular structure of Purine and pyrimidine bases ▪ Nucleosides and Nucleotides ▪ Synthesis of Purine nucleotides ▪ Synthesis of Pyrimidine nucleotides ▪ Flowchart of biosynthesis of nucleotides  3 Introduction ▪ Pyrimidine and purine are the names of the parent compounds of two types of nitrogen-containing heterocyclic aromatic compounds. N N N N N N H Pyrimidine Purine Important Purines 4 ▪ Adenine and guanine are the principal purines of both DNA and RNA. NH2 O N N HN N H2N N N N N H H Guanine Adenine ▪ Caffeine (coffee) and theobromine (cocoa) are naturally occurring purines.  5 Important Pyrimidines ▪ Pyrimidines that occur in DNA are cytosine and thymine. Cytosine and uracil are the pyrimidines in RNA. O NH2 O CH3 HN HN HN O N N O N O H H H Uracil Thymine Cytosine  Nucleosides and Nucleotides 6 Nucleoside is a structure formed by the combination of nitrogen base and sugar where as Nucleotides are phosphoric acid esters of nucleosides. N2 base Sugars Nucleoside Nucleos Phospho Nucleotides ide ric acid Adenine Deoxyribose/ Adenosine Adenosine Phosphoric Adenylate Ribose acid (AMP) Guanine Deoxiribose/R Guanosine Guanosine Phosphoric Guanylate ( ibose acid GMP) Thymidine Phosphoric Thymidylate ( Thymine Deoxyribose Thymidine acid TMP) Cytidine Phosphoric Cytidylate Cytosine Deoxyribose/ Cytidine acid (CMP) Ribose Uridine Phosphoric Uridylate (UMP) Uracil Ribose Uridine acid  7 Synthesis of Purine Nucleotides Denovo Synthesis of purine base step synthesis by step on the Site- Liver, ribose 5- cytosol phosphate Synthesis of purine nucleotides Salvage Addition of ribose 5-phosphate to the pathway preformed purine bases or addition Site - Plastid of phosphate to the purine nucleosides  8 Sources of Different Atoms of Purine Ring De novo Synthesis of Purine And 9 Pyrimidine Purine Synthesis 10 ▪ STEP-1 ▪ STEP-2 ▪ STEP-3 STEP-4 11 ▪ STEP-5 ▪ STEP-5 ▪ STEP-6 12 ▪ STEP-7 ▪ STEP-8 STEP-9 13 ▪ STEP-10 STEP-11 14 15  Salvage Pathway 16 It refers to the formation of purine nucleotides by the 1. Addition of ribose phosphate ( from PRPP) to the preformed purine bases. 2. Addition of phosphate to the preformed purine nucleosides. Significance ✓Salvage pathway provide a pathway for the utilization of purine bases derived from diet (exogenous) and normal turnover of the nucleic acids. ✓In erythrocytes, denovo syntheis of purine nucleotides does not occur because of absence of PRPP amidotransferase. The requirement of purine nucleotides is met by the salvage pathway.  17 Synthesis of Pyrimidine Nucleotides Synthesis of Denovo pyrimidine synthesis nucleotide refers to the formation of Site- liver, cytosol, pyrimidine ring mitochondria structure followed Synthesis by the addition of ribose phosphate. of pyrimidine nucleotides Salvage Formation of pyrimidine pathway nucleotides from Site - Plastid pyrimidine bases Sources of different atoms of pyrimidine 18 ring  Pyrimidine Synthesis O 19 2 ATP + HCO3- + Glutamine + H2O C HN CH 2 ADP + Carbamoyl O Glutamate + Phosphate C C Pi Synthetase II C O N CH COO HN PRPP PPi 2- O3P O CH2 NH2 O C C Orotate Phosphoribosyl H H  O C O N Transferase H H H COO OH OH O PO3-2 Orotidine-5'-monophosphate Orotate (OMP) Carbamoyl Phosphate Aspartate Reduced Aspartate Transcarbamoylase Quinone OMP Dihydroorotate Decarboxylase (ATCase) Dehydrogenase Pi CO2 Quinone O O O HO C C C HN CH CH2 NH2 HN CH2 H2O C CH O N C CH C CH O N Dihydroorotase O N 2- O3P O CH2 H O COO H COO H H  Carbamoyl Aspartate H H Dihydroorotate OH OH Uridine Monophosphate (UMP) 20 21 Salvage pathway 22  23 Summary 24