Biosynthesis of Purines and Pyrimidines
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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.
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Metabolism of Purine & Pyrimidine nucleotide
This document summarizes the biosynthesis pathways of purine and pyrimidine nucleotides. It discusses:
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Amino acid degradation 1
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Carbon Skeleton Formation:
Amino acids are composed of a central carbon atom (alpha carbon) bonded to a hydrogen atom, an amino group (NH2), a carboxyl group (COOH), and a side chain (R group) specific to each amino acid.
The carbon skeletons of amino acids are derived from intermediates of glycolysis, citric acid cycle, and pentose phosphate pathway.
Transamination:
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This reaction is catalyzed by aminotransferases or transaminases, and pyridoxal phosphate (PLP) acts as a cofactor.
Specific Pathways for Essential Amino Acids:
Essential amino acids, which cannot be synthesized de novo by the body, have specific biosynthetic pathways.
For example, lysine and methionine biosynthesis involve the aspartate family pathway, while valine, leucine, and isoleucine biosynthesis occur through the branched-chain amino acid (BCAA) pathway.
Non-Essential Amino Acid Biosynthesis:
Non-essential amino acids can be synthesized by the body through various pathways.
For instance, glutamate serves as a precursor for the synthesis of several amino acids, including proline, arginine, and ornithine.
Specific Amino Acid Biosynthesis Pathways:
Serine and Glycine Biosynthesis:
Serine is derived from 3-phosphoglycerate and can be converted to glycine.
The enzyme serine hydroxymethyltransferase plays a key role in interconverting serine and glycine.
Histidine Biosynthesis:
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Tyrosine and Phenylalanine Biosynthesis:
The shikimate pathway is essential for the biosynthesis of aromatic amino acids, including tyrosine and phenylalanine.
Chorismate is a key intermediate in this pathway.
Arginine Biosynthesis:
Arginine biosynthesis involves the urea cycle and the ornithine biosynthetic pathway.
Citrulline serves as a key intermediate in these processes.
Proline Biosynthesis:
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Regulation of Amino Acid Biosynthesis:
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LYSINE METABOLISM
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PYRIMIDINE SYNTHESIS
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General Pathway of Amino Acid Biosynthesis:
Amino acid biosynthesis involves complex metabolic pathways that differ for each amino acid. However, a general overview can be provided:
Carbon Skeleton Formation:
Amino acids are composed of a central carbon atom (alpha carbon) bonded to a hydrogen atom, an amino group (NH2), a carboxyl group (COOH), and a side chain (R group) specific to each amino acid.
The carbon skeletons of amino acids are derived from intermediates of glycolysis, citric acid cycle, and pentose phosphate pathway.
Transamination:
A crucial step in amino acid biosynthesis is the transamination reaction, where an amino group is transferred from an amino acid donor to an alpha-keto acid acceptor.
This reaction is catalyzed by aminotransferases or transaminases, and pyridoxal phosphate (PLP) acts as a cofactor.
Specific Pathways for Essential Amino Acids:
Essential amino acids, which cannot be synthesized de novo by the body, have specific biosynthetic pathways.
For example, lysine and methionine biosynthesis involve the aspartate family pathway, while valine, leucine, and isoleucine biosynthesis occur through the branched-chain amino acid (BCAA) pathway.
Non-Essential Amino Acid Biosynthesis:
Non-essential amino acids can be synthesized by the body through various pathways.
For instance, glutamate serves as a precursor for the synthesis of several amino acids, including proline, arginine, and ornithine.
Specific Amino Acid Biosynthesis Pathways:
Serine and Glycine Biosynthesis:
Serine is derived from 3-phosphoglycerate and can be converted to glycine.
The enzyme serine hydroxymethyltransferase plays a key role in interconverting serine and glycine.
Histidine Biosynthesis:
Histidine biosynthesis involves a unique pathway that starts with phosphoribosyl pyrophosphate (PRPP) and includes several enzymatic steps.
Tyrosine and Phenylalanine Biosynthesis:
The shikimate pathway is essential for the biosynthesis of aromatic amino acids, including tyrosine and phenylalanine.
Chorismate is a key intermediate in this pathway.
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Pyrimidine synthesis occurs in six steps:
1) Carbamoyl phosphate is synthesized from glutamine and bicarbonate
2) Carbamoyl aspartate is formed from carbamoyl phosphate and aspartate
3) Dihydroorotate is formed via ring closure of carbamoyl aspartate
4) Dihydroorotate is oxidized to orotate
5) Orotate reacts with PRPP to form OMP
6) OMP is decarboxylated to form UMP
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Nucleotides are organic molecules that serve as subunits of nucleic acids like DNA and RNA. They are composed of a sugar, phosphate group, and a nitrogenous base. Nucleotides contain either a purine or pyrimidine base and are found in cells and nuclei. They function as precursors to DNA/RNA and in cellular energy processes. Nucleotides are synthesized through de novo or salvage pathways. De novo pathways fully synthesize nucleotides from basic precursors, while salvage pathways recover nucleotides from existing bases. The 10-step de novo purine pathway builds the purine ring on ribose-5-phosphate. The 6-step pyrimidine pathway first forms the pyrimidine ring
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PURINE METABOLISM LECTURE.ppt
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This document discusses the biosynthesis of purines and pyrimidines. It explains that purines and pyrimidines are synthesized through de novo and salvage pathways. The de novo pathway involves multiple enzyme-catalyzed steps to convert simple precursors into the complex purine and pyrimidine nucleotides. The salvage pathway recovers bases and nucleotides formed during RNA and DNA degradation. The document provides detailed steps for purine biosynthesis and synthesis of AMP and GMP from IMP. It also briefly discusses pyrimidine biosynthesis and inhibitors of purine synthesis.
Biosynthesis of purine & pyrimidine
This document discusses the biosynthesis of purines and pyrimidines. It explains that purines and pyrimidines are synthesized through de novo and salvage pathways. The de novo pathway involves multiple enzyme-catalyzed steps to convert simple precursors into the complex purine and pyrimidine nucleotides. This includes converting ribose-5-phosphate into inosine monophosphate (IMP) through 10 steps for purine synthesis. IMP is then used to synthesize adenine monophosphate (AMP) and guanine monophosphate (GMP). The salvage pathway recovers bases and nucleotides from degraded DNA and RNA. Pyrimidine synthesis is described as simpler than purine synthesis.
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Molecular biology is the study of biological phenomena at the molecular level, particularly proteins, nucleic acids, and enzymes. In the early 1950s, knowledge of protein structure enabled the description of DNA structure as a double helix. The discovery of restriction enzymes in the 1970s allowed for recombinant DNA technology, which molecular biologists use to isolate and modify genes. DNA is made up of nucleotides containing nitrogenous bases and a sugar-phosphate backbone. The four bases in DNA—adenine, guanine, cytosine, and thymine—bind together in base pairs across the double helix in a complementary manner.
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Biosynthesis of Purines and Pyrimidines
- 1. BIOSYNTHESIS OF PURINES AND PYRIMIDINES
- 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.
- 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.
- 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
- 15. (1) amido phosphoribosyltransferase, (2) GAR synthetase, (3) GAR formyl transferase, (4) FGAM synthetase, (5) AIR synthetase, (6) AIR carboxylase, (7) SAICAR synthetase, (8) adenylosuccinate lyase, (9) AICAR formyl transferase, (10) IMP cyclohydrolase, (11) SAMP synthetase, (12) adenylosuccinase, (13) IMP dehydrogenase, (14) GMP synthetase.
- 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).
- 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.
- 20. N1,C6,C5,C4-Aspartate C2-Bicarbonate N3-Glutamine
- 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.