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B.Tech Biotechnology 4th Semester Biochemistry Metabolism.
Typology: Study Guides, Projects, Research
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๏ N1 of purine is derived from amino group of aspartate. ๏ C2 & C8 from formate of N 10
๏ 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.
๏ 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.
10
๏ The imidazole ring of the purine is closed in an ATP dependent reaction to yield 5- aminoimidazole ribosyl 5 - phosphate. ๏ The reaction is catalyzed by synthetase. ๏ Incorporation of CO2 (carboxylation) occurs to yield aminoimidazole carboxylate ribosyl 5 - phosphate. ๏ The reaction is catalyzed by carboxylase.
๏ Adenosuccinate lyase cleaves off fumarate & only the amino group of aspartate is retained to yield aminoimidazole 4-carboxamide ribosyl 5 - phosphate. ๏ N 10
๏ 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.
๏ 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.
๏ 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).
๏ The nucleoside monophosphates (AMP & GMP) converted to the corresponding di & triphosphates. ๏ 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