De novo and salvage pathway of nucleotides synthesis.pptx

This slides explains Metabolism topic "De novo and salvage pathway of nucleotides synthesis. In which synthesis of Purines and pyrimidines synthesis has been occurred. In last there is a difference between these two pathways.

1. De novo & Salvage pathways of Nucleotides Presented By: Tehseen Sajid Bite212107014 Munawar Ali Bite212107016 Submitted to : Mam Munaza Tahir

2. Objectives De novo pathway f or purines synthesis Salvage pathway for pyrimidines What is nucleotides? Diff b/w these two pathways De novo pathway for Pyrimidines Two pathways (de novo & salvage pathways for synthesis of nucleotides? Salvag e pathway for purines synthesis Purines and pyrimidines ?

3. What is nucleotides Nucleotides are the building blocks of nucleic acids. As nucleic acid is polymer of nucleotides which contain: -Phosphate group -Deoxyribose/ribose sugar -Nitrogenous base Nucleoside: -Deoxyribose/ribose sugar -Nitrogenous base

4. Purines and pyrimidines Purines and pyrimidines are major parts of nucleotides which are building blocks of nucleic acids:  DNA and RNA. Purine and pyrimidine are nitrogen-containing bases. Purines have a six-membered and a five-membered nitrogen-containing ring fused to each other. Pyrimidines have only a six-membered nitrogen-containing ring.( thymine, uracil, cytosine). Uracil is found only in RNA.

5. Purines and pyrimidines are synthesized via two principal routes:   In  De novo  pathway, purines and pyrimidines are synthesized from the simple molecules, especially from amino acid precursors.  In the salvage pathway, purines and pyrimidines are synthesized from intermediates from the degradative pathways. De novo pathway Salvage pathway

6. De Novo Pathway for Purines synthesis  De novo synthesis of purine nucleotides refers to the process that utilizes small molecules to produce purine nucleotides. The detailed pathway of purine biosynthesis was worked out primarily by Buchanan and G. Robert Greenberg in the 1950s. Moreover, the de novo pathway is the main pathway that synthesizes purine nucleotides.

7. Location Purine synthesis occurs in all tissues. The major site of purine synthesis is in the liver and, to a limited extent, in the brain. Substrates:  Ribose-5-phosphate; glycine; glutamine; H 2 O; ATP; CO 2 ; aspartate. Products:  GMP; AMP; glutamate; fumarate; H 2 O.

8. Explanation In de novo pathway, ribose -5-phosphate works as the starting material. Then, it reacts with ATP and converts into phosphoribosyl pyrophosphate (PRPP) by PRPP synthetase Next, glutamine donates its amide group to PRPP and converts it to 5-phosphoribosylamine.  This reaction is catalyzed by glutamine PRPP amidino transferase. A series of nine reactions results in the formation of IMP (Inosine 5′-monophosphate). IMP can then be transformed either to GMP or AMP by IMP dehydrogenase  IMP is the immediate precursor molecule of the adenosine monophosphate (AMP) and guanosine monophosphate (GMP), which are purine nucleotides.

9. Salvage pathway for Purines synthesis Salvage pathway of purine nucleotide synthesis refers to the process of synthesizing nucleotides from purine bases and purine nucleosides. Ensures the recycling of purines formed by degradation of nucleotides.  Purine bases and purine nucleotides are constantly produced in the cells as a result of the metabolism of nucleotides such as polynucleotide degradation. Moreover, these bases and nucleosides also enter our body by the food we consume.

10. Location Purine synthesis via the salvage pathways occurs in all tissues. It is especially important in the brain and the bone marrow. Substrates:  Hypoxanthine; PRPP; guanine; adenine. Products:  GMP; AMP; IMP.

11. Explanation Bases from degraded nucleic acids can be converted back into purine nucleotides via the salvage pathways. Hypoxanthine can be combined with PRPP (which acts as the donor of ribose-5 phosphate) to form IMP in a reaction catalyzed by Hypoxanthine-guanine phosphoribosyl transferase (HGPRT). IMP can subsequently be transformed into AMP or GMP via the last few steps of the pathway of de novo purine synthesis. HGPRT also catalyzes the reaction which combines PRPP with guanine to form GMP. Adenine phosphoribosyl transferase converts adenine and PRPP to form AMP.

12. De novo pathway for Pyrimidines synthesis Pyrimidine De novo synthesis is simpler than purine synthesis since pyrimidine molecules are simple. Biosynthesis of pyrimidine  nucleotides  can occur by a de novo pathway or by the reutilization of preformed pyrimidine bases or ribonucleosides (salvage pathway).

13. Location De novo pyrimidine synthesis occurs in the cytosol of cells in all tissues. Substrates : CO 2 ; glutamine; ATP; Aspartate; H 2 O; NAD + ; Phosphoribosyl pyrophosphate (PRPP). Products:  UTP; CTP; glutamate; NADH; CO 2

14. Explanation Pyrimidine De novo synthesis is simpler than purine synthesis since pyrimidine molecules are simple. Glutamine’s amide nitrogen and carbon dioxide provide atoms 2 and 3 of the pyrimidine ring. Other four atoms of the ring are supplied by aspartate. PRPP supplies the sugar-phosphate portion of the molecule. Salvaging pyrimidines is catalyzed by nucleoside phosphorylases (uridine phosphorylase and deoxythymidine phosphorylase) and nucleoside kinases (thymidine kinase and uridine kinase).

15. Pathway

16. Salvage pathway for pyrimidines synthesis Pyrimidines can be salvaged from orotic acid, uracil, and thymine but not from cytosine.

17. Explanation

18. Difference

19. Any Query?