1) Purines and pyrimidines are synthesized through de novo and salvage pathways to produce nucleotides that are the building blocks of nucleic acids.
2) The de novo pathway builds the nucleotides from simple precursors in multi-step reactions requiring energy, while the salvage pathway recycles nucleotides.
3) Purine synthesis begins with IMP and involves 11 enzymatic steps to form the purine ring. Pyrimidine synthesis is simpler, forming the 6-membered ring first before attaching to ribose-5-phosphate in 6 steps to form UMP.
2. Nucleic acids DNA and RNA are polymers
of nucleotide units.
Each nucleotide is composed of a nitrogenous
base,a pentose sugar and a phosphate group.
Purines and pyrimidines are 2 classes of
nucleotides in cells.
3.
4.
5. 1. Purine and pyrimidine nucleotides are major energy
carriers(ATP /GTP).
2. Subunits of nucleic acids
3. Precursors for the synthesis of nucleotide cofactors
such as NAD .
4. Components of coenzymes(NAD/FAD)
5. Signal transduction(cyclicAMP/GMP)
6. It is a multistep enzyme catalyzed process where substrates
are converted into complex products in living organisms.
In biosynthesis ,simple compounds are modified ,converted
into other compounds,or joined together to form
macromolecules.
The pathways for the synthesis of nucleotides in plant cells
are similar to those found in animals and microorganisms.
7. There are two principal routes for the synthesis of
nucleotides: the de novo and the salvage pathways.
Using 5- phosphoribosyl-1-pyrophosphate (PRPP),
the de novo pathway enzymes build purine and
pyrimidine nucleotides from “scratch” using simple
molecules such as CO2, amino acids and
tetrahydrofolate.
This route of nucleotide synthesis has a high
requirement for energy as compared that of the
salvage pathway.
8.
9. De novo pathway-Biochemical pathway where
nucleotides are synthesized from new simple
precursor molecules.
Salvage pathway- The salvage cycle interconverts
purine bases, nucleosides and nucleotides released as
by-products of cellular metabolism or from the
catabolism of nucleic acids or nucleotide cofactors.
10. BUILDING BLOCKS OF A PURINE NUCLEUS-
N1- Aspartate
C2 and C8-Formate
N3 and N9-Glutamine
C4,C5,N7-Glycine
C6-Bicarbonate
11. Purines are synthesized as ribo-
nucleotides rather than free bases.
Purines are derived from Inosine -
5-monophosphate.
Thus purine synthesis starts with
IMP synthesis.
Inosine-5-monophosphate(IMP)
12. IMP is synthesized in 11 steps from simple
precursors.
1. Ribose-5-phosphate activation from PRPP
2. Acquisition of N9 atom of purine from Glutamine
3. Acquisition of C4,C5,N7 atoms of purine from a Glycine
4. Acquisition of C8 tom of purine from Formate
5. Acquisition of N3 atom of purine from Glutamine
6. Purine Imidazole ring formation
7. Acquisition of C6 atom of purine from Bicarbonate
8. Acquisition of N1 atom of purine from Aspartate
9. Elimination of Fumarate
10. Acquisition of C2 atom of purine
11. Cyclization to form IMP
17. The salvage cycle interconverts purine bases,
nucleosides and nucleotides released as by-products of
cellular metabolism or from the catabolism of nucleic
acids or nucleotide cofactors.
This strategy for purine nucleotide synthesis is
energetically favorable for a cell since only one
salvage reaction requires ATP (phosphorylation of
nucleosides to nucleotides).
18.
19. Simpler than purine synthesis
Involves 6 steps
6-membered pyrimidine ring is formed first and then attached to
Ribose-5-monophosphate.
Uridine-5-monophosphate is the precursor.
Out of 6 enzymes involved in the pathway,5 are in cytosol and one
on the outer surface of inner mitochondrial membrane.
23. As the de novo pyrimidine biosynthetic pathway is energy consuming,
cells reutilize pyrimidine bases and nucleosides derived from the
preformed nucleotides .
Of the bases, only uracil is directly reused via a specific
phosphoribosyltransferase whereas the pyrimidine nucleosides, uridine,
cytidine and deoxycytidine are exclusively salvaged to their respective
nucleotides, UMP, CMP and dCMP.
High activity of uridine/cytidine kinase and nucleoside
phosphotransferase may contribute the salvage of these nucleosides.
