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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.
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PYRIMIDINE SYNTHESIS
Biosynthesis of pyrimidine nucleotides can occur by a de novo pathway or by the reutilization of preformed pyrimidine bases or ribonucleosides (salvage pathway).
The pyrimidine synthesis is a similar process than that of purines. In the de novo synthesis of pyrimidines, the ring is synthesized first and then it is attached to a ribose-phosphate to for a pyrimidine nucleotide.
PYRIMIDINE DEGRADATION & DISORDERS
The document summarizes pyrimidine nucleotide degradation and the salvage pathway. It also describes orotic aciduria, a rare metabolic disorder characterized by orotic acid in urine, anemia, and stunted growth. Orotic aciduria can be caused by deficiencies in enzymes involved in pyrimidine synthesis or a defect in the urea cycle enzyme ornithine transcarbamoylase, which diverts carbamoyl phosphate to increased orotic acid synthesis. The condition can be treated by supplementing with cytidine or uridine.
Metabolism of nucleotides
This document provides an overview of pyrimidine and purine nucleotide metabolism. It discusses the de novo synthesis and salvage pathways for both purine and pyrimidine nucleotides. The key enzymes and reactions involved in synthesis and regulation are described. Disorders resulting from defects in purine and pyrimidine metabolism are also reviewed, including gout, Lesch-Nyhan syndrome, immunodeficiencies, and infantile autism.
BIOSYNTHESIS OF PYRIMIDINES.pptx
BIOSYNTHESIS OF PYRIMIDINES
SALVAGE PATHWAY
DE NOVO PATHWAY
SYNTHESIS OF OTHER PYRIMIDINE NUCLEOTIDES
IMPORTANCE
Essential building blocks of nucleic acids
Biologically very important heterocycles
Used in anti-biotics, used as anti-bacterial and anti-fungal also
Derivatives of pyrimidine also possess good anti-viral properties
Pyrimidine metabolism
The document summarizes pyrimidine nucleotide biosynthesis. It is a shorter pathway than purine biosynthesis, with the base made first then attached to ribose-5-phosphate. Only two precursors, aspartate and glutamine/HCO3-, contribute to the six-membered ring. The product is orotidylic acid (OMP). OMP is further converted to UMP and other pyrimidine nucleotides. Regulation differs between bacteria and animals. Orotic aciduria is caused by defects in OMP formation and is treated with uridine/cytidine supplementation, which provides an alternative route to pyrimidine nucleotide synthesis.
biosynthesis of purine
Purines are nitrogenous bases that are components of nucleotides and nucleic acids. They are synthesized through two pathways: de novo synthesis and the salvage pathway. De novo synthesis involves the biosynthesis of IMP from simple precursor molecules through a regulated biochemical pathway. Abnormalities in purine metabolism can cause human diseases like gout, Lesch-Nyhan syndrome, and adenosine deaminase deficiency.
Metabolism of nucleotides new
1. The document summarizes purine and pyrimidine nucleotide metabolism, including the de novo and salvage pathways of purine biosynthesis, regulation of purine synthesis, conversion of ribonucleotides to deoxyribonucleotides, degradation of purines to uric acid, and disorders of purine metabolism like hyperuricemia, gout, and Lesch-Nyhan syndrome.
2. Key aspects of purine synthesis covered include the formation of IMP from PRPP as the first purine nucleotide, and the subsequent generation of AMP and GMP from IMP. Degradation of purines culminates in the production of uric acid as the final product in humans.
3. Disorders discussed arise
Purine and Pyrimidine biosynthesis
Nucleotide Biosynthesis involves 2 processes. one is Denovo synthesis and other is Salvage pathway. An outline of both the processes has given in this presentation.
Recommended
PYRIMIDINE SYNTHESIS
Biosynthesis of pyrimidine nucleotides can occur by a de novo pathway or by the reutilization of preformed pyrimidine bases or ribonucleosides (salvage pathway).
The pyrimidine synthesis is a similar process than that of purines. In the de novo synthesis of pyrimidines, the ring is synthesized first and then it is attached to a ribose-phosphate to for a pyrimidine nucleotide.
PYRIMIDINE DEGRADATION & DISORDERS
The document summarizes pyrimidine nucleotide degradation and the salvage pathway. It also describes orotic aciduria, a rare metabolic disorder characterized by orotic acid in urine, anemia, and stunted growth. Orotic aciduria can be caused by deficiencies in enzymes involved in pyrimidine synthesis or a defect in the urea cycle enzyme ornithine transcarbamoylase, which diverts carbamoyl phosphate to increased orotic acid synthesis. The condition can be treated by supplementing with cytidine or uridine.
Metabolism of nucleotides
This document provides an overview of pyrimidine and purine nucleotide metabolism. It discusses the de novo synthesis and salvage pathways for both purine and pyrimidine nucleotides. The key enzymes and reactions involved in synthesis and regulation are described. Disorders resulting from defects in purine and pyrimidine metabolism are also reviewed, including gout, Lesch-Nyhan syndrome, immunodeficiencies, and infantile autism.
BIOSYNTHESIS OF PYRIMIDINES.pptx
BIOSYNTHESIS OF PYRIMIDINES
SALVAGE PATHWAY
DE NOVO PATHWAY
SYNTHESIS OF OTHER PYRIMIDINE NUCLEOTIDES
IMPORTANCE
Essential building blocks of nucleic acids
Biologically very important heterocycles
Used in anti-biotics, used as anti-bacterial and anti-fungal also
Derivatives of pyrimidine also possess good anti-viral properties
Pyrimidine metabolism
The document summarizes pyrimidine nucleotide biosynthesis. It is a shorter pathway than purine biosynthesis, with the base made first then attached to ribose-5-phosphate. Only two precursors, aspartate and glutamine/HCO3-, contribute to the six-membered ring. The product is orotidylic acid (OMP). OMP is further converted to UMP and other pyrimidine nucleotides. Regulation differs between bacteria and animals. Orotic aciduria is caused by defects in OMP formation and is treated with uridine/cytidine supplementation, which provides an alternative route to pyrimidine nucleotide synthesis.
biosynthesis of purine
Purines are nitrogenous bases that are components of nucleotides and nucleic acids. They are synthesized through two pathways: de novo synthesis and the salvage pathway. De novo synthesis involves the biosynthesis of IMP from simple precursor molecules through a regulated biochemical pathway. Abnormalities in purine metabolism can cause human diseases like gout, Lesch-Nyhan syndrome, and adenosine deaminase deficiency.
Metabolism of nucleotides new
1. The document summarizes purine and pyrimidine nucleotide metabolism, including the de novo and salvage pathways of purine biosynthesis, regulation of purine synthesis, conversion of ribonucleotides to deoxyribonucleotides, degradation of purines to uric acid, and disorders of purine metabolism like hyperuricemia, gout, and Lesch-Nyhan syndrome.
2. Key aspects of purine synthesis covered include the formation of IMP from PRPP as the first purine nucleotide, and the subsequent generation of AMP and GMP from IMP. Degradation of purines culminates in the production of uric acid as the final product in humans.
3. Disorders discussed arise
Purine and Pyrimidine biosynthesis
Nucleotide Biosynthesis involves 2 processes. one is Denovo synthesis and other is Salvage pathway. An outline of both the processes has given in this presentation.
Purine degradation
This document summarizes purine biosynthesis and degradation. Purine is synthesized through an 11 step pathway forming IMP, the parent nucleotide. IMP is then used to synthesize AMP and GMP. Purines are broken down to uric acid through a multi-step process. Gout is caused by excessive uric acid formation due to increased purine biosynthesis or decreased excretion leading to uric acid crystal deposition in joints.
Pyrimidine Biosynthesis
The six-step de novo pyrimidine biosynthesis pathway converts aspartate and bicarbonate into UMP. The first step produces carbamoyl phosphate from glutamine and bicarbonate. Carbamoyl phosphate then reacts with aspartate to form carbamoyl aspartate. Ring closure produces dihydroorotate, which is oxidized to orotate. Orotate is attached to PRPP to form OMP. OMP is decarboxylated to produce the final product UMP. UMP can be further modified to CTP and other pyrimidine nucleotides. The pathway is regulated by feedback inhibition of early enzymes by end products.
Nucleotide Chemistry
The slide has some brief introduction to nucleotide chemistry, History, General features of nucleotides, Nomenclature, Individual properties of bases, Classification
and Synthetic analogues of biomedical importance.
Pyrimidine Synthesis and Degradation
This document summarizes the de novo synthesis of pyrimidine nucleotides. It describes the precursors and reactions involved in synthesizing the pyrimidine ring and then attaching it to ribose phosphate to form the pyrimidine nucleotides CMP, UMP and TMP. It also discusses the conversion of UDP to CTP and dTMP, the regulation of pyrimidine synthesis, salvage pathways, catabolism of pyrimidines, and the genetic disorder orotic aciduria caused by a defect in the enzyme UMP synthase.
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.
Nucleotide metabolism (r ) 1
The document discusses nucleotide metabolism, specifically purine and pyrimidine nucleotide biosynthesis. It describes how purine nucleotides like IMP are synthesized through multi-step pathways requiring various precursors. IMP then branches into AMP and GMP synthesis pathways. Purine synthesis is regulated by controlling levels of PRPP and at the first two rate-limiting steps. The synthesis of pyrimidine nucleotides also utilizes PRPP and multi-step pathways to synthesize nucleotides from precursors.
SERINE & THREONINE METABOLISM
Serine is a non-essential amino acid that can be synthesized from glycolysis intermediates. It participates in one-carbon metabolism by donating methylene groups, and it is involved in the synthesis of several other amino acids, phospholipids, and sphingolipids. Serine can be converted to pyruvate through transamination and deamination reactions. Threonine is an essential amino acid that can be cleaved to form glycine, acetaldehyde, and derivatives that enter the citric acid cycle or form pyruvate and lactate. Both amino acids play important roles in biosynthesis as carriers of phosphate groups.
PYRUVATE DEHYDROGENASE COMPLEX (PDH-MULTI-ENZYME COMPLEX)
Pyruvate is converted to acetyl CoA by the pyruvate dehydrogenase (PDH) complex in the mitochondria. PDH is a multi-enzyme complex containing five coenzymes and three enzymes that catalyzes the oxidative decarboxylation of pyruvate. This generates acetyl CoA, NADH, and FADH2, with the NADH and FADH2 contributing to ATP production through oxidative phosphorylation. PDH activity is regulated by phosphorylation/dephosphorylation and end-product inhibition by acetyl CoA and NADH.
Fad – Flavin Adenine Dinucleotide
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PYRIMIDINE SYNTHESIS
The document summarizes the de novo synthesis of pyrimidine nucleotides in three steps. First, carbamoyl phosphate and aspartate condense to form carbamoyl aspartate. Second, the pyrimidine ring forms and is further modified through a series of reactions to eventually form orotidine monophosphate. Third, OMP undergoes reactions to form the pyrimidine nucleotides UMP, UDP, UTP, CTP, and through additional steps, dUMP and dTMP. Key enzymes involved include carbamoyl phosphate synthetase, aspartate transcarbamoylase, and OMP decarboxylase. Feedback inhibition regulates the process.
De novo and salvage pathway of purines
Jayati Mishra presented on the de novo and salvage pathways of purines under the guidance of Pradip Hirapue. The presentation discussed:
1) The de novo pathway synthesizes purine nucleotides from simple precursors through a two-stage process forming IMP and then converting it to AMP or GMP.
2) The salvage pathway recycles purine bases and nucleosides obtained from the diet or cell turnover to form nucleotides.
3) Both pathways work together to synthesize the purine nucleotides needed for nucleic acid synthesis, with the salvage pathway playing a larger role in certain tissues.
Catabolism of pyrimidine nucleotides
Pyrimidine nucleotides are catabolized into highly water soluble compounds unlike purines. The end products of pyrimidine metabolism are carbon dioxide, ammonia, beta-alanine, and beta-aminoisobutyrate. Beta-aminoisobutyrate is transaminated into other compounds that can enter the citric acid cycle or be used for fatty acid synthesis.
Pyrimidine bio synthesis
This document summarizes pyrimidine biosynthesis and degradation. It discusses that pyrimidines are synthesized from CO2, NH3, and aspartate. The ring is completed before being linked to ribose-5-phosphate. Key steps include the formation of carbamoyl phosphate, carbamoyl aspartate, dihydroorotate, UMP, UDP, UTP, and finally CTP from UTP and glutamine. UMP is converted to UTP through two phosphorylation reactions requiring ATP. The document provides an overview of de novo pyrimidine nucleotide synthesis from precursors and through enzymatic steps.
Metabolism of Phenylalanine and Tyrosine
Phenylalanine, tyrosine, and tryptophan are aromatic amino acids whose metabolism produces many biologically important compounds. Deficiencies in their metabolic pathways can cause inborn errors. Phenylalanine and tryptophan are nutritionally essential, while tyrosine can be synthesized from phenylalanine. They are converted into catecholamines, thyroid hormones, and melanin pigment. Errors in their metabolism can lead to disorders like phenylketonuria, tyrosinemia, and albinism.
Vitamine B1 Thaimine Pyrophosphate
This document summarizes information about vitamin B1 (thiamine) and its active coenzyme form, thiamine pyrophosphate (TPP). It discusses the history of thiamine discovery and its chemical structure. Thiamine is converted to TPP in the liver and intestinal mucosa by the enzyme thiamine pyrophosphokinase using ATP. TPP acts as a coenzyme, transferring aldehyde groups in metabolic reactions. Sources of thiamine are mentioned and a deficiency can cause beriberi. Functions include roles in growth, nervous system maintenance, and metabolism.
Nucleotide metabolism
introduction of Purine and Pyrimidine metabolism, biosynthesis and degradation of nucleotides, biological functions and metabolic disorders, chemical analogues and therapeutic drugs, uric acid metabolism
Biosynthesis of Purine Ribonucleotide, Gout
This document summarizes purine nucleotide synthesis pathways. It discusses two main pathways: de novo synthesis and salvage pathway. De novo synthesis involves assembling the purine ring from various precursors on ribose-5-phosphate. The salvage pathway recycles purine bases and nucleosides obtained from dietary sources or nucleic acid degradation. The committed step in de novo synthesis is controlled by the concentration of PRPP, which depends on the availability of ribose-5-phosphate and the activity of PRPP synthase.
Biosynthesis of purines and pyrimidines new
this is the information about biosynthesis of purines and pyrimidines how they are synthesized via various pathways
Gluconeogenesis and glycogenolysis
This document summarizes the metabolic pathways of gluconeogenesis and glycogenolysis. It explains that gluconeogenesis synthesizes glucose from non-carbohydrate precursors through a series of steps that are largely the reverse of glycolysis, with three bypass reactions. Glycogenolysis breaks down glycogen stores in the liver and muscle into glucose through cleavage of glucose monomers by glycogen phosphorylase and subsequent conversion to glucose-6-phosphate. Both pathways are regulated by hormones like glucagon and epinephrine.
co and post translation modification, by
1-Introduction
2-Protein modifications
[A] Folding
1-Chaperon mediated
2-Enzymatic
[B] Cleavage
[C] Glycosylation
[D] Attachment of Lipids
[E] Proteolysis
3-Conclusion
4-Reference
Metabolism of Nucleic Acids
1. Nucleic acids consist of nitrogen bases, pentose sugars, and phosphates. The pentose sugar is D-ribose in RNA and 2-deoxy D-ribose in DNA.
2. Purine nucleotides are synthesized through a de novo pathway where inosine monophosphate (IMP) is synthesized from basic building blocks like aspartate, glycine, and glutamine and later converted to AMP and GMP.
3. Pyrimidine nucleotides are synthesized by first forming orotidine monophosphate from aspartate, carbamoyl phosphate, and glutamine, which is then converted to UMP and other pyrimidine nucleotides.
Purine nuecleotide
1. The document discusses the metabolism of purine and pyrimidine nucleotides, including their biosynthesis, degradation, and disorders related to purine metabolism such as gout and Lesch-Nyhan syndrome.
2. Purine nucleotides are synthesized through both a de novo synthesis pathway that builds the purine ring from simple precursors, and a salvage pathway that recycles purine bases. A key early intermediate is IMP, which is converted to AMP and GMP.
3. Uric acid is the final product of purine degradation in humans and high levels can cause gout. Lesch-Nyhan syndrome results from HGPRT deficiency disrupting the salvage pathway.
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Purine degradation
This document summarizes purine biosynthesis and degradation. Purine is synthesized through an 11 step pathway forming IMP, the parent nucleotide. IMP is then used to synthesize AMP and GMP. Purines are broken down to uric acid through a multi-step process. Gout is caused by excessive uric acid formation due to increased purine biosynthesis or decreased excretion leading to uric acid crystal deposition in joints.
Pyrimidine Biosynthesis
The six-step de novo pyrimidine biosynthesis pathway converts aspartate and bicarbonate into UMP. The first step produces carbamoyl phosphate from glutamine and bicarbonate. Carbamoyl phosphate then reacts with aspartate to form carbamoyl aspartate. Ring closure produces dihydroorotate, which is oxidized to orotate. Orotate is attached to PRPP to form OMP. OMP is decarboxylated to produce the final product UMP. UMP can be further modified to CTP and other pyrimidine nucleotides. The pathway is regulated by feedback inhibition of early enzymes by end products.
Nucleotide Chemistry
The slide has some brief introduction to nucleotide chemistry, History, General features of nucleotides, Nomenclature, Individual properties of bases, Classification
and Synthetic analogues of biomedical importance.
Pyrimidine Synthesis and Degradation
This document summarizes the de novo synthesis of pyrimidine nucleotides. It describes the precursors and reactions involved in synthesizing the pyrimidine ring and then attaching it to ribose phosphate to form the pyrimidine nucleotides CMP, UMP and TMP. It also discusses the conversion of UDP to CTP and dTMP, the regulation of pyrimidine synthesis, salvage pathways, catabolism of pyrimidines, and the genetic disorder orotic aciduria caused by a defect in the enzyme UMP synthase.
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.
Nucleotide metabolism (r ) 1
The document discusses nucleotide metabolism, specifically purine and pyrimidine nucleotide biosynthesis. It describes how purine nucleotides like IMP are synthesized through multi-step pathways requiring various precursors. IMP then branches into AMP and GMP synthesis pathways. Purine synthesis is regulated by controlling levels of PRPP and at the first two rate-limiting steps. The synthesis of pyrimidine nucleotides also utilizes PRPP and multi-step pathways to synthesize nucleotides from precursors.
SERINE & THREONINE METABOLISM
Serine is a non-essential amino acid that can be synthesized from glycolysis intermediates. It participates in one-carbon metabolism by donating methylene groups, and it is involved in the synthesis of several other amino acids, phospholipids, and sphingolipids. Serine can be converted to pyruvate through transamination and deamination reactions. Threonine is an essential amino acid that can be cleaved to form glycine, acetaldehyde, and derivatives that enter the citric acid cycle or form pyruvate and lactate. Both amino acids play important roles in biosynthesis as carriers of phosphate groups.
PYRUVATE DEHYDROGENASE COMPLEX (PDH-MULTI-ENZYME COMPLEX)
Pyruvate is converted to acetyl CoA by the pyruvate dehydrogenase (PDH) complex in the mitochondria. PDH is a multi-enzyme complex containing five coenzymes and three enzymes that catalyzes the oxidative decarboxylation of pyruvate. This generates acetyl CoA, NADH, and FADH2, with the NADH and FADH2 contributing to ATP production through oxidative phosphorylation. PDH activity is regulated by phosphorylation/dephosphorylation and end-product inhibition by acetyl CoA and NADH.
Fad – Flavin Adenine Dinucleotide
flavin adenine dinucleotide (FAD) is a redox cofactor, more specifically a prosthetic group, involved in several important reactions in metabolism.
PYRIMIDINE SYNTHESIS
The document summarizes the de novo synthesis of pyrimidine nucleotides in three steps. First, carbamoyl phosphate and aspartate condense to form carbamoyl aspartate. Second, the pyrimidine ring forms and is further modified through a series of reactions to eventually form orotidine monophosphate. Third, OMP undergoes reactions to form the pyrimidine nucleotides UMP, UDP, UTP, CTP, and through additional steps, dUMP and dTMP. Key enzymes involved include carbamoyl phosphate synthetase, aspartate transcarbamoylase, and OMP decarboxylase. Feedback inhibition regulates the process.
De novo and salvage pathway of purines
Jayati Mishra presented on the de novo and salvage pathways of purines under the guidance of Pradip Hirapue. The presentation discussed:
1) The de novo pathway synthesizes purine nucleotides from simple precursors through a two-stage process forming IMP and then converting it to AMP or GMP.
2) The salvage pathway recycles purine bases and nucleosides obtained from the diet or cell turnover to form nucleotides.
3) Both pathways work together to synthesize the purine nucleotides needed for nucleic acid synthesis, with the salvage pathway playing a larger role in certain tissues.
Catabolism of pyrimidine nucleotides
Pyrimidine nucleotides are catabolized into highly water soluble compounds unlike purines. The end products of pyrimidine metabolism are carbon dioxide, ammonia, beta-alanine, and beta-aminoisobutyrate. Beta-aminoisobutyrate is transaminated into other compounds that can enter the citric acid cycle or be used for fatty acid synthesis.
Pyrimidine bio synthesis
This document summarizes pyrimidine biosynthesis and degradation. It discusses that pyrimidines are synthesized from CO2, NH3, and aspartate. The ring is completed before being linked to ribose-5-phosphate. Key steps include the formation of carbamoyl phosphate, carbamoyl aspartate, dihydroorotate, UMP, UDP, UTP, and finally CTP from UTP and glutamine. UMP is converted to UTP through two phosphorylation reactions requiring ATP. The document provides an overview of de novo pyrimidine nucleotide synthesis from precursors and through enzymatic steps.
Metabolism of Phenylalanine and Tyrosine
Phenylalanine, tyrosine, and tryptophan are aromatic amino acids whose metabolism produces many biologically important compounds. Deficiencies in their metabolic pathways can cause inborn errors. Phenylalanine and tryptophan are nutritionally essential, while tyrosine can be synthesized from phenylalanine. They are converted into catecholamines, thyroid hormones, and melanin pigment. Errors in their metabolism can lead to disorders like phenylketonuria, tyrosinemia, and albinism.
Vitamine B1 Thaimine Pyrophosphate
This document summarizes information about vitamin B1 (thiamine) and its active coenzyme form, thiamine pyrophosphate (TPP). It discusses the history of thiamine discovery and its chemical structure. Thiamine is converted to TPP in the liver and intestinal mucosa by the enzyme thiamine pyrophosphokinase using ATP. TPP acts as a coenzyme, transferring aldehyde groups in metabolic reactions. Sources of thiamine are mentioned and a deficiency can cause beriberi. Functions include roles in growth, nervous system maintenance, and metabolism.
Nucleotide metabolism
introduction of Purine and Pyrimidine metabolism, biosynthesis and degradation of nucleotides, biological functions and metabolic disorders, chemical analogues and therapeutic drugs, uric acid metabolism
Biosynthesis of Purine Ribonucleotide, Gout
This document summarizes purine nucleotide synthesis pathways. It discusses two main pathways: de novo synthesis and salvage pathway. De novo synthesis involves assembling the purine ring from various precursors on ribose-5-phosphate. The salvage pathway recycles purine bases and nucleosides obtained from dietary sources or nucleic acid degradation. The committed step in de novo synthesis is controlled by the concentration of PRPP, which depends on the availability of ribose-5-phosphate and the activity of PRPP synthase.
Biosynthesis of purines and pyrimidines new
this is the information about biosynthesis of purines and pyrimidines how they are synthesized via various pathways
Gluconeogenesis and glycogenolysis
This document summarizes the metabolic pathways of gluconeogenesis and glycogenolysis. It explains that gluconeogenesis synthesizes glucose from non-carbohydrate precursors through a series of steps that are largely the reverse of glycolysis, with three bypass reactions. Glycogenolysis breaks down glycogen stores in the liver and muscle into glucose through cleavage of glucose monomers by glycogen phosphorylase and subsequent conversion to glucose-6-phosphate. Both pathways are regulated by hormones like glucagon and epinephrine.
co and post translation modification, by
1-Introduction
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Metabolism of Nucleic Acids
1. Nucleic acids consist of nitrogen bases, pentose sugars, and phosphates. The pentose sugar is D-ribose in RNA and 2-deoxy D-ribose in DNA.
2. Purine nucleotides are synthesized through a de novo pathway where inosine monophosphate (IMP) is synthesized from basic building blocks like aspartate, glycine, and glutamine and later converted to AMP and GMP.
3. Pyrimidine nucleotides are synthesized by first forming orotidine monophosphate from aspartate, carbamoyl phosphate, and glutamine, which is then converted to UMP and other pyrimidine nucleotides.
Purine nuecleotide
1. The document discusses the metabolism of purine and pyrimidine nucleotides, including their biosynthesis, degradation, and disorders related to purine metabolism such as gout and Lesch-Nyhan syndrome.
2. Purine nucleotides are synthesized through both a de novo synthesis pathway that builds the purine ring from simple precursors, and a salvage pathway that recycles purine bases. A key early intermediate is IMP, which is converted to AMP and GMP.
3. Uric acid is the final product of purine degradation in humans and high levels can cause gout. Lesch-Nyhan syndrome results from HGPRT deficiency disrupting the salvage pathway.
Nucleic Acid Metabolism
The document provides an overview of nucleic acid metabolism and the synthesis of purines and pyrimidines. It discusses how nucleotides serve as building blocks for nucleic acids and how they are synthesized through both de novo and salvage pathways. The key steps in purine synthesis include the production of IMP from PRPP and glutamine, followed by conversion to AMP and GMP. Purines can also be salvaged from nucleic acid breakdown. Deoxyribonucleotides are synthesized from ribonucleotides by the enzyme ribonucleotide reductase. Defects in nucleotide synthesis can cause diseases.
Nucleotide chemistry & metabolism
This document discusses nucleotide chemistry and metabolism. It begins by describing the composition and functions of nucleotides, including their role as phosphate donors in phosphorylation reactions. It then details the de novo biosynthesis of purine nucleotides, which involves 11 steps building up to the formation of inosine monophosphate (IMP) from various small molecule precursors. IMP is then converted to other purine nucleotides like AMP and GMP. The synthesis of purine nucleotides is regulated by feedback inhibition. The document also discusses disorders of purine metabolism like hyperuricemia and gout.
PURINE METABOLISM LECTURE.ppt
This document discusses purine metabolism, including the biosynthesis and catabolism of purines. It covers several key points:
- Nucleotides are composed of a nitrogenous base, pentose sugar, and phosphate groups, and are building blocks for DNA and RNA. They also participate in energy production and carbohydrate metabolism.
- Purines are synthesized through de novo and salvage pathways. De novo synthesis builds the purine ring from simple precursors, while salvage pathways recover purines from nucleic acid breakdown.
- Adenine and guanine are formed through a series of reactions adding carbon and nitrogen atoms to ribose-5-phosphate. IMP is converted to AMP and GMP, which
BIOSYNTHESIS OF PURINE NUCLEOTIDES
1. The document summarizes purine nucleotide synthesis, which involves multiple enzymatic reactions using substrates like aspartate, glutamine, glycine, and CO2 to build the purine ring structure on ribose 5-phosphate.
2. Liver is the major site of de novo purine synthesis, while erythrocytes and brain must salvage purines due to their inability to synthesize them.
3. Feedback inhibition regulates purine synthesis at committed steps, and analogs like 6-mercaptopurine can inhibit pathways leading to AMP and GMP formation.
final_n.a_metabolism.pptx
This document discusses nucleoprotein metabolism and the biosynthesis of purine nucleotides. It describes how purines are synthesized de novo through a multi-step pathway beginning with ribose-5-phosphate. The pathway involves 11 steps to produce inosine monophosphate (IMP) as the first purine nucleotide. IMP is then converted to AMP and GMP. The process requires energy and nitrogen/carbon sources like glutamine, glycine, and formate. Key regulatory enzymes control the pathway in response to levels of purine nucleotides like IMP, AMP and GMP.
Purine and pyrimidine synthesis
1. Nucleotides consist of a nitrogenous base, sugar (ribose or deoxyribose), and phosphate. Purines and pyrimidines are synthesized via de novo or salvage pathways to form nucleotides.
2. Purine synthesis occurs in multiple steps starting from PRPP, with the purine ring built step-by-step. Pyrimidine synthesis involves first forming the pyrimidine ring and then attaching it to ribose-5-phosphate.
3. Errors in purine synthesis can cause diseases like gout, which results from excess uric acid in the blood due to defects in purine metabolism or uric acid excretion. Several drugs target purine synthesis
Introduction to nucleic acid, chemistry of nucleotiides , july 2020
This document provides an introduction to nucleic acids, their components, and chemistry. It can be summarized as follows:
1. Nucleic acids are high molecular weight polymers composed of nucleotides linked by phosphodiester bonds. The nucleotides contain a pentose sugar, phosphate group, and nitrogenous base.
2. DNA contains deoxyribose and RNA contains ribose. The nitrogenous bases in DNA are adenine, guanine, cytosine, and thymine, while in RNA thymine is replaced by uracil.
3. Nucleotides are the monomers that make up nucleic acids. They contain a nucleoside (pentose sugar + nitrogenous base), and one or more phosphate groups
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This document summarizes the synthesis of purines and pyrimidines, which are nitrogenous bases that along with pentose sugars and phosphate groups make up nucleotides. It describes that purines adenine and guanine and pyrimidines cytosine, thymine, and uracil are components of both DNA and RNA. The synthesis of purine nucleotides involves ten steps to form inosine monophosphate, followed by two additional steps to form adenosine monophosphate and guanosine monophosphate. Pyrimidine synthesis involves six steps beginning with carbamoyl phosphate and aspartate to form a pyrimidine ring and ultimately uridine monophosphate. Rate of DNA synthesis can
Metabolism of nucleotides
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chemistry NUCLEOTIDES
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Nucleotides chemistry and metabolism
This document discusses nucleotides, their chemistry and metabolism. It covers the following key points:
- Nucleotides are composed of a nitrogenous base, a pentose sugar (ribose or deoxyribose), and phosphate groups. They are precursors to nucleic acids DNA and RNA.
- Purines and pyrimidines are the nitrogenous bases present in nucleotides. Adenine, guanine, cytosine and thymine are the major bases.
- Nucleotides are synthesized through two pathways - de novo synthesis which builds purine rings from simple precursors, and the salvage pathway which recycles purines.
- The major sites of purine synthesis are the liver and degradation
Metabolism of Purine & Pyrimidine nucleotide
This document summarizes the biosynthesis pathways of purine and pyrimidine nucleotides. It discusses:
1) Purine biosynthesis occurs in two phases - first the synthesis of aminoimidazole ribosyl-5-phosphate (VII) from ribose 5-phosphate, then the synthesis of inosine monophosphate (IMP, XII) from aminoimidazole ribosyl-5-phosphate.
2) Pyrimidine biosynthesis differs in that the pyrimidine ring is first synthesized, followed by attachment to ribose phosphate. It begins with carbamoyl phosphate and involves intermediates like orotic acid and orotidylate before forming uridine monophosph
Pyrimidine pdf converted
1. Pyrimidine nucleotides are synthesized through a simpler process than purines, using aspartate, glutamine and CO2 to form the pyrimidine ring.
2. The ring is first synthesized and then attached to ribose-5-phosphate, unlike purines which are built upon pre-existing ribose-5-phosphate.
3. Uridine monophosphate (UMP) is the first true pyrimidine ribonucleotide formed through a series of reactions, and is later phosphorylated to form other pyrimidine nucleotides.
Pyrimidine pdf
This document summarizes pyrimidine nucleotide metabolism. Pyrimidine synthesis involves multiple steps including formation of carbamoyl phosphate from glutamine and bicarbonate, condensation with aspartate, ring closure, transfer of ribose phosphate, decarboxylation and phosphorylation to form UMP. UMP is further converted to UDP, UTP, CTP and TMP. Pyrimidines can also be synthesized through a salvage pathway. The synthesis is regulated by feedback inhibition of key enzymes by end products. Disorders include orotic aciduria due to deficiencies in the pyrimidine synthesis pathway and Reye's syndrome which involves secondary orotic aciduria.
Pyrimidine pdf
This document summarizes pyrimidine nucleotide metabolism. Pyrimidine synthesis involves multiple steps including formation of carbamoyl phosphate from glutamine and bicarbonate, condensation with aspartate, ring closure, transfer of ribose phosphate, decarboxylation and phosphorylation to form UMP. UMP is further converted to UDP, UTP, CTP and TMP. Pyrimidines can also be synthesized through a salvage pathway using preformed bases. The synthesis is regulated by feedback inhibition of key enzymes by end products. Disorders include orotic aciduria due to deficiencies in the pyrimidine synthesis pathway and Reye's syndrome which involves secondary orotic aciduria.
Handouts molecular biology-1
This document summarizes biologically important nucleotides and their functions. It discusses the composition of nucleotides and their roles in DNA, RNA, and various biochemical functions. Specific nucleotides are described, including adenosine nucleotides (ATP, ADP, AMP, cAMP), guanosine nucleotides (GTP, GDP, GMP, cGMP), uridine nucleotides (UTP, UDP, UMP, UDP-G), and cytidine nucleotides (CTP, CDP, CMP). It also discusses purine and pyrimidine metabolism, including biosynthesis, degradation, salvage pathways, and disorders like hyperuricemia, gout, and Lesch-Nyhan syndrome. The regulation and enzymes involved in
Similar to biosynthesisof-190408140232.pdf (20)
Introduction to nucleic acid, chemistry of nucleotiides , july 2020
Introduction to nucleic acid, chemistry of nucleotiides , july 2020
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This document discusses chromatin and transposable genetic elements. It defines chromatin as a combination of DNA and proteins that condenses to form chromosomes during cell division in eukaryotes. It is located in the cell nucleus and functions to compact DNA. The document also defines transposable elements as mobile genetic sequences that can move within and between genomes. It describes different types of transposable elements found in prokaryotes and eukaryotes, such as insertion sequences, transposons, Ty elements, SINEs, and LINEs. These elements can cause genetic changes by inserting into genes or regulatory sequences.
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Transposons is.pptx
Chromatin is a complex of DNA and proteins found in the nucleus of eukaryotic cells. It functions to compact DNA into chromosomes. Chromatin is made up of nucleosomes, which consist of DNA wound around histone proteins. Nucleosomes can further condense to form chromatin fibers. During cell division, chromatin condenses even further to form chromosomes. Chromatin is involved in processes like DNA replication, transcription, repair, and recombination. There are two main types: euchromatin, which decondenses during interphase, and heterochromatin, which remains condensed. Transposable elements are DNA sequences that can change positions within a genome. They are found in both prokaryotes and eukary
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Transposons is.pptx
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1 ppt copy.pptx
This document provides an introduction to foodborne pathogens written by Anima Verma, an MSc student of Biotechnology. It discusses various bacterial, viral and toxic infections that can be transmitted through food, including Staphylococcus, Bacillus cereus, Salmonella, E. coli, Hepatitis A, and toxins produced by algae. It emphasizes the importance of proper hygiene, cooking, storage and handling of food to prevent contamination and transmission of foodborne illnesses.
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The document describes IntEnz, an integrated relational enzyme database maintained by EBI. It provides information on the history and development of enzyme classification systems, an overview of the content and features of IntEnz, including browsing and searching enzyme entries which contain the official enzyme nomenclature from NC-IUBMB along with other linked data. IntEnz data can be accessed and downloaded in several formats.
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Alternate Wetting and Drying - Climate Smart Agriculture
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PPT on Alternate Wetting and Drying presented at the three-day 'Training and Validation Workshop on Modules of Climate Smart Agriculture (CSA) Technologies in South Asia' workshop on April 22, 2024. Describing and Interpreting an Immersive Learning Case with the Immersion Cub...
Current descriptions of immersive learning cases are often difficult or impossible to compare. This is due to a myriad of different options on what details to include, which aspects are relevant, and on the descriptive approaches employed. Also, these aspects often combine very specific details with more general guidelines or indicate intents and rationales without clarifying their implementation. In this paper we provide a method to describe immersive learning cases that is structured to enable comparisons, yet flexible enough to allow researchers and practitioners to decide which aspects to include. This method leverages a taxonomy that classifies educational aspects at three levels (uses, practices, and strategies) and then utilizes two frameworks, the Immersive Learning Brain and the Immersion Cube, to enable a structured description and interpretation of immersive learning cases. The method is then demonstrated on a published immersive learning case on training for wind turbine maintenance using virtual reality. Applying the method results in a structured artifact, the Immersive Learning Case Sheet, that tags the case with its proximal uses, practices, and strategies, and refines the free text case description to ensure that matching details are included. This contribution is thus a case description method in support of future comparative research of immersive learning cases. We then discuss how the resulting description and interpretation can be leveraged to change immersion learning cases, by enriching them (considering low-effort changes or additions) or innovating (exploring more challenging avenues of transformation). The method holds significant promise to support better-grounded research in immersive learning.
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This is a short talk that I gave at the Banff International Research Station workshop on Modeling and Theory in Population Biology. The idea is to try to understand how the burden of natural selection relates to the amount of information that selection puts into the genome.
It's based on the first part of this research paper:
The cost of information acquisition by natural selection
Ryan Seamus McGee, Olivia Kosterlitz, Artem Kaznatcheev, Benjamin Kerr, Carl T. Bergstrom
bioRxiv 2022.07.02.498577; doi: https://doi.org/10.1101/2022.07.02.498577
Candidate young stellar objects in the S-cluster: Kinematic analysis of a sub...
Context. The observation of several L-band emission sources in the S cluster has led to a rich discussion of their nature. However, a definitive answer to the classification of the dusty objects requires an explanation for the detection of compact Doppler-shifted Brγ emission. The ionized hydrogen in combination with the observation of mid-infrared L-band continuum emission suggests that most of these sources are embedded in a dusty envelope. These embedded sources are part of the S-cluster, and their relationship to the S-stars is still under debate. To date, the question of the origin of these two populations has been vague, although all explanations favor migration processes for the individual cluster members. Aims. This work revisits the S-cluster and its dusty members orbiting the supermassive black hole SgrA* on bound Keplerian orbits from a kinematic perspective. The aim is to explore the Keplerian parameters for patterns that might imply a nonrandom distribution of the sample. Additionally, various analytical aspects are considered to address the nature of the dusty sources. Methods. Based on the photometric analysis, we estimated the individual H−K and K−L colors for the source sample and compared the results to known cluster members. The classification revealed a noticeable contrast between the S-stars and the dusty sources. To fit the flux-density distribution, we utilized the radiative transfer code HYPERION and implemented a young stellar object Class I model. We obtained the position angle from the Keplerian fit results; additionally, we analyzed the distribution of the inclinations and the longitudes of the ascending node. Results. The colors of the dusty sources suggest a stellar nature consistent with the spectral energy distribution in the near and midinfrared domains. Furthermore, the evaporation timescales of dusty and gaseous clumps in the vicinity of SgrA* are much shorter ( 2yr) than the epochs covered by the observations (≈15yr). In addition to the strong evidence for the stellar classification of the D-sources, we also find a clear disk-like pattern following the arrangements of S-stars proposed in the literature. Furthermore, we find a global intrinsic inclination for all dusty sources of 60 ± 20◦, implying a common formation process. Conclusions. The pattern of the dusty sources manifested in the distribution of the position angles, inclinations, and longitudes of the ascending node strongly suggests two different scenarios: the main-sequence stars and the dusty stellar S-cluster sources share a common formation history or migrated with a similar formation channel in the vicinity of SgrA*. Alternatively, the gravitational influence of SgrA* in combination with a massive perturber, such as a putative intermediate mass black hole in the IRS 13 cluster, forces the dusty objects and S-stars to follow a particular orbital arrangement. Key words. stars: black holes– stars: formation– Galaxy: center– galaxies: star formation
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The binding of cosmological structures by massless topological defects
Assuming spherical symmetry and weak field, it is shown that if one solves the Poisson equation or the Einstein field
equations sourced by a topological defect, i.e. a singularity of a very specific form, the result is a localized gravitational
field capable of driving flat rotation (i.e. Keplerian circular orbits at a constant speed for all radii) of test masses on a thin
spherical shell without any underlying mass. Moreover, a large-scale structure which exploits this solution by assembling
concentrically a number of such topological defects can establish a flat stellar or galactic rotation curve, and can also deflect
light in the same manner as an equipotential (isothermal) sphere. Thus, the need for dark matter or modified gravity theory is
mitigated, at least in part.
JAMES WEBB STUDY THE MASSIVE BLACK HOLE SEEDS
The pathway(s) to seeding the massive black holes (MBHs) that exist at the heart of galaxies in the present and distant Universe remains an unsolved problem. Here we categorise, describe and quantitatively discuss the formation pathways of both light and heavy seeds. We emphasise that the most recent computational models suggest that rather than a bimodal-like mass spectrum between light and heavy seeds with light at one end and heavy at the other that instead a continuum exists. Light seeds being more ubiquitous and the heavier seeds becoming less and less abundant due the rarer environmental conditions required for their formation. We therefore examine the different mechanisms that give rise to different seed mass spectrums. We show how and why the mechanisms that produce the heaviest seeds are also among the rarest events in the Universe and are hence extremely unlikely to be the seeds for the vast majority of the MBH population. We quantify, within the limits of the current large uncertainties in the seeding processes, the expected number densities of the seed mass spectrum. We argue that light seeds must be at least 103 to 105 times more numerous than heavy seeds to explain the MBH population as a whole. Based on our current understanding of the seed population this makes heavy seeds (Mseed > 103 M⊙) a significantly more likely pathway given that heavy seeds have an abundance pattern than is close to and likely in excess of 10−4 compared to light seeds. Finally, we examine the current state-of-the-art in numerical calculations and recent observations and plot a path forward for near-future advances in both domains.
Anti-Universe And Emergent Gravity and the Dark Universe
Recent theoretical progress indicates that spacetime and gravity emerge together from the entanglement structure of an underlying microscopic theory. These ideas are best understood in Anti-de Sitter space, where they rely on the area law for entanglement entropy. The extension to de Sitter space requires taking into account the entropy and temperature associated with the cosmological horizon. Using insights from string theory, black hole physics and quantum information theory we argue that the positive dark energy leads to a thermal volume law contribution to the entropy that overtakes the area law precisely at the cosmological horizon. Due to the competition between area and volume law entanglement the microscopic de Sitter states do not thermalise at sub-Hubble scales: they exhibit memory effects in the form of an entropy displacement caused by matter. The emergent laws of gravity contain an additional ‘dark’ gravitational force describing the ‘elastic’ response due to the entropy displacement. We derive an estimate of the strength of this extra force in terms of the baryonic mass, Newton’s constant and the Hubble acceleration scale a0 = cH0, and provide evidence for the fact that this additional ‘dark gravity force’ explains the observed phenomena in galaxies and clusters currently attributed to dark matter.
Discovery of An Apparent Red, High-Velocity Type Ia Supernova at 𝐳 = 2.9 wi...
We present the JWST discovery of SN 2023adsy, a transient object located in a host galaxy JADES-GS
+
53.13485
−
27.82088
with a host spectroscopic redshift of
2.903
±
0.007
. The transient was identified in deep James Webb Space Telescope (JWST)/NIRCam imaging from the JWST Advanced Deep Extragalactic Survey (JADES) program. Photometric and spectroscopic followup with NIRCam and NIRSpec, respectively, confirm the redshift and yield UV-NIR light-curve, NIR color, and spectroscopic information all consistent with a Type Ia classification. Despite its classification as a likely SN Ia, SN 2023adsy is both fairly red (
�
(
�
−
�
)
∼
0.9
) despite a host galaxy with low-extinction and has a high Ca II velocity (
19
,
000
±
2
,
000
km/s) compared to the general population of SNe Ia. While these characteristics are consistent with some Ca-rich SNe Ia, particularly SN 2016hnk, SN 2023adsy is intrinsically brighter than the low-
�
Ca-rich population. Although such an object is too red for any low-
�
cosmological sample, we apply a fiducial standardization approach to SN 2023adsy and find that the SN 2023adsy luminosity distance measurement is in excellent agreement (
≲
1
�
) with
Λ
CDM. Therefore unlike low-
�
Ca-rich SNe Ia, SN 2023adsy is standardizable and gives no indication that SN Ia standardized luminosities change significantly with redshift. A larger sample of distant SNe Ia is required to determine if SN Ia population characteristics at high-
�
truly diverge from their low-
�
counterparts, and to confirm that standardized luminosities nevertheless remain constant with redshift.
ESA/ACT Science Coffee: Diego Blas - Gravitational wave detection with orbita...
ESA/ACT Science Coffee: Diego Blas - Gravitational wave detection with orbita...Advanced-Concepts-Team
Presentation in the Science Coffee of the Advanced Concepts Team of the European Space Agency on the 07.06.2024.
Speaker: Diego Blas (IFAE/ICREA)
Title: Gravitational wave detection with orbital motion of Moon and artificial
Abstract:
In this talk I will describe some recent ideas to find gravitational waves from supermassive black holes or of primordial origin by studying their secular effect on the orbital motion of the Moon or satellites that are laser ranged.Applied Science: Thermodynamics, Laws & Methodology.pdf
When I was asked to give a companion lecture in support of ‘The Philosophy of Science’ (https://shorturl.at/4pUXz) I decided not to walk through the detail of the many methodologies in order of use. Instead, I chose to employ a long standing, and ongoing, scientific development as an exemplar. And so, I chose the ever evolving story of Thermodynamics as a scientific investigation at its best.
Conducted over a period of >200 years, Thermodynamics R&D, and application, benefitted from the highest levels of professionalism, collaboration, and technical thoroughness. New layers of application, methodology, and practice were made possible by the progressive advance of technology. In turn, this has seen measurement and modelling accuracy continually improved at a micro and macro level.
Perhaps most importantly, Thermodynamics rapidly became a primary tool in the advance of applied science/engineering/technology, spanning micro-tech, to aerospace and cosmology. I can think of no better a story to illustrate the breadth of scientific methodologies and applications at their best.
The debris of the ‘last major merger’ is dynamically young
The Milky Way’s (MW) inner stellar halo contains an [Fe/H]-rich component with highly eccentric orbits, often referred to as the
‘last major merger.’ Hypotheses for the origin of this component include Gaia-Sausage/Enceladus (GSE), where the progenitor
collided with the MW proto-disc 8–11 Gyr ago, and the Virgo Radial Merger (VRM), where the progenitor collided with the
MW disc within the last 3 Gyr. These two scenarios make different predictions about observable structure in local phase space,
because the morphology of debris depends on how long it has had to phase mix. The recently identified phase-space folds in Gaia
DR3 have positive caustic velocities, making them fundamentally different than the phase-mixed chevrons found in simulations
at late times. Roughly 20 per cent of the stars in the prograde local stellar halo are associated with the observed caustics. Based
on a simple phase-mixing model, the observed number of caustics are consistent with a merger that occurred 1–2 Gyr ago.
We also compare the observed phase-space distribution to FIRE-2 Latte simulations of GSE-like mergers, using a quantitative
measurement of phase mixing (2D causticality). The observed local phase-space distribution best matches the simulated data
1–2 Gyr after collision, and certainly not later than 3 Gyr. This is further evidence that the progenitor of the ‘last major merger’
did not collide with the MW proto-disc at early times, as is thought for the GSE, but instead collided with the MW disc within
the last few Gyr, consistent with the body of work surrounding the VRM.
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PPT on Direct Seeded Rice presented at the three-day 'Training and Validation Workshop on Modules of Climate Smart Agriculture (CSA) Technologies in South Asia' workshop on April 22, 2024.
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biosynthesisof-190408140232.pdf
- 2. Introduction Biosynthesis is a multi-step, enzyme-catalyzed process where substrates are converted into more complex products in living organisms. In biosynthesis, simple compounds are modified, converted into other compounds, or joined together to form macromolecules. This process often consists of metabolic pathways. The purines are built upon a pre-existing ribose 5- phosphate. Liver is the major site for purine nucleotide synthesis. Erythrocytes, polymorphonuclear leukocytes & brain cannot produce purines.
- 3. Pathways • There are Two pathways for the synthesis of nucleotides: 1. De-novo synthesis: Biochemical pathway where nucleotides are synthesized from new simple precursor molecules 2. Salvage pathway: Used to recover bases and nucleotides formed during the degradation of RNA and DNA.
- 7. Step involved in purine biosynthesis (Adenine & Guanine) • Ribose-5-phosphate, of carbohydrate metabolism is the starting material for purine nucleotide synthesis. • It reacts with ATP to form phosphoribosyl pyrophosphate (PRPP). • Glutamine transfers its amide nitrogen to PRPP to replace pyrophosphate & produce 5- phosphoribosylamine. Catalysed by PRPP glutamyl amidotransferase. • This reaction is the committed.
- 8. • Phosphoribosylamine reacts with glycine in the presence of ATP to form glycinamide ribosyl 5- phosphate or glycinamide ribotide (GAR).Catalyzed by synthetase. • N10-Formyl tetrahydrofolate donates the formyl group & the product formed is formylglycinamide ribosyl 5-phosphate. Catalyzed by formyltransferase. • Glutamine transfers the second amido amino group to produce formylglycinamidine ribosyl 5- phosphate. Catalyzed by synthetase.
- 9. • The imidazole ring of the purine is closed in an ATP dependent reaction to yield 5- aminoimidazole ribosyl 5-phosphate. Catalyzed by synthetase. • Incorporation of CO2 (carboxylation) occurs to yield aminoimidazole carboxylate ribosyl 5- phosphate. Catalyzed by carboxylase. • Does not require the vitamin biotin or ATP. • Aspartate condenses with the aminoimidazole carboxylate ribosyl 5- phosphate to form aminoimidazole 4- succinylcarboxamide ribosyl 5-phosphate. Catalyzed by synthetase.
- 10. • Adenosuccinatelyase cleaves off fumarate & only the amino group of aspartate is retained to yield aminoimidazole 4-carboxamide ribosyl 5- phosphate. • N10-Formyl tetrahydrofolate donates one carbon moiety to produce 5- formaminoimidazole 4- carboxamide ribosyl 5- phosphate. Catalyzed by formyltransferase. • The final reaction catalyzed by cyclohydrolase leads to ring closure with an elimination of water molecule. • The product obtained is Inosine Monophosphate (IMP), the parent purine nucleotide from which other purine nucleotides can be synthesized.
- 12. Synthesis of AMP & GMP from IMP Synthesis of AMP: Ionosine monophosphate (IMP) is the immediate precursor for the formation of AMP & GMP. Aspartate condenses with IMP in the presence of GTP to produce adenylsuccinate which, on cleavage, forms AMP.
- 13. Synthesis of GMP: IMP undergoes NAD+ dependent dehydrogenation to form xanthosine monophosphate (XMP). Glutamine then transfers amide nitrogen to xanthosine monophosphate (XMP) to produce GMP. 6-Mercaptopurine is an inhibitor of the synthesis of AMP & GMP. It acts on the enzyme adenylsuccinase (of AMP pathway) & IMP dehydrogenase (of GMP pathway).
- 14. Synthesis of AMP & GMP
- 15. Salvage Pathway
- 16. Inhibitor of purine biosynthesis • Folic acid (THF) is essential for the synthesis of purine nucleotides. • Sulfonamides are the structural analogs of Para- aminobenzoic acid (PABA). • These sulfa drugs can inhibit the synthesis of folic acid by microorganisms. This indirectly reduces the synthesis of purines & nucleic acids (DNA & RNA). • The structural analogs of folic acid (e.g. methotrexate), used to control cancer.
- 17. • Azaserine (diazo acetyl-L-Serine) is a glutamine antagonist & inhibits reactions involving glutamine. • Other synthetic nucleotide analogues used as anticancer agents are 6-thio guanine & 8- aza guanine.
- 18. Biosynthesis of pyrimidine (Uracil, Cytosine & Thymine) De novo synthesis of pymiridine: • Biosynthesis of pyrimidine is simple than that of purine.
- 24. Important links for study • http://cancerres.aacrjournals.org/content/can res/37/9/3080.full.pdf • http://www.jbc.org/content/202/1/241.full.pd f • http://www.jbc.org/content/early/2018/01/0 3/jbc.M117.809459.full.pdf • http://www.jbc.org/content/253/19/6794.full. pdf