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Purine Nucleotide Synthesis: A Comprehensive Guide, Study Guides, Projects, Research of Biochemistry

B.Tech Biotechnology 4th Semester Biochemistry Metabolism.

Typology: Study Guides, Projects, Research

2020/2021

Available from 07/22/2021

Devashish_Kalambe
Devashish_Kalambe ๐Ÿ‡ฎ๐Ÿ‡ณ

12 documents

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๏‚ž N1 of purine is derived from amino group of aspartate. ๏‚ž C2 & C8 from formate of N 10

  • formyl THF. ๏‚ž N3 & N9 are obtained from amide group of glutamine. ๏‚ž C4, C5 & N7 are contributed by glycine. ๏‚ž C6 directly comes from CO2.

๏‚ž The purines are built upon a pre-existing ribose 5 - phosphate. ๏‚ž Liver is the major site for purine nucleotide synthesis. ๏‚ž Erythrocytes, polymorphonuclear leukocytes & brain cannot produce purines.

๏‚ž Ribose 5 - phosphate, of carbohydrate metabolism is the starting material for purine nucleotide synthesis. ๏‚ž It reacts with ATP to form phosphoribosyl pyrophosphate (PRPP). ๏‚ž Glutamine transfers its amide nitrogen to PRPP to replace pyrophosphate & produce 5- phosphoribosylamine.

๏‚ž N

10

  • Formyl tetrahydrofolate donates the formyl group & the product formed is formylglycinamide ribosyl 5 - phosphate. ๏‚ž The reaction is catalyzed by formyltransferase. ๏‚ž Glutamine transfers the second amido amino group to produce formylglycinamidine ribosyl 5 - phosphate. ๏‚ž The reaction is catalyzed by synthetase.

๏‚ž The imidazole ring of the purine is closed in an ATP dependent reaction to yield 5- aminoimidazole ribosyl 5 - phosphate. ๏‚ž The reaction is catalyzed by synthetase. ๏‚ž Incorporation of CO2 (carboxylation) occurs to yield aminoimidazole carboxylate ribosyl 5 - phosphate. ๏‚ž The reaction is catalyzed by carboxylase.

๏‚ž Adenosuccinate lyase cleaves off fumarate & only the amino group of aspartate is retained to yield aminoimidazole 4-carboxamide ribosyl 5 - phosphate. ๏‚ž N 10

  • Formyl tetrahydrofolate donates a one- carbon moiety to produce 5- formaminoimidazole 4-carboxamide ribosyl 5 - phosphate. ๏‚ž Catalyzed by formyltransferase.

๏‚ž The final reaction catalyzed by cyclohydrolase leads to ring closure with an elimination of water molecule. ๏‚ž The product obtained is inosine monophosphate (IMP), the parent purine nucleotide from which other purine nucleotides can be synthesized.

๏‚ž Synthesis of AMP: ๏‚ž Ionosine monophosphate (IMP) is the immediate precursor for the formation of AMP & GMP. ๏‚ž Aspartate condenses with IMP in the presence of GTP to produce adenylsuccinate which, on cleavage, forms AMP.

๏‚ž 6 - Mercaptopurine is an inhibitor of the synthesis of AMP & GMP. ๏‚ž It acts on the enzyme adenylsuccinase (of AMP pathway). ๏‚ž IMP dehydrogenase (of GMP pathway).

๏‚ž The nucleoside monophosphates (AMP & GMP) converted to the corresponding di & triphosphates. ๏‚ž This is achieved by the transfer of phosphate group from ATP, catalysed by nucleoside monophosphate (NMP) kinases & nucleoside diphosphate (NDP) kinases.

Nucleoside monophosphate (AMP, GMP) Nucleoside diphosphate (ADP, GDP) Nucleoside triphosphate (ATP, GTP) ATP ADP NMP kinase NDP kinase ATP ADP