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BIOC/DENT/PHCY 230 LECTURE 6. Nucleotides. found in DNA and RNA used for energy (ATP and GTP) building blocks for coenzymes (NADH). Building blocks for nucleotides. Two classes of bases. Two types of ribose. Synthesis of nucleotides.
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BIOC/DENT/PHCY 230 LECTURE 6
Nucleotides • found in DNA and RNA • used for energy (ATP and GTP) • building blocks for coenzymes (NADH)
Synthesis of nucleotides • nucleotide bases can be recycled or synthesised de novo • purine bases are synthesised on ribose • pyrimidine bases are synthesisedindependent of ribose
AMP Synthesis of PRPP • PRPP contributes ribose phosphate to nucleotides • formation catalysed by PRPP synthetase PRPP synthetase is allosterically inhibited by AMP, ADP and GDP.
De novo purine synthesis Glutamine donates an amide to initiate purine synthesis A whole glycine is added to the nitrogen
The coenzyme tetrahydrofolate donates a formyl group Glutamine donates a second amide
Aspartate is added in an energy dependent reaction This is analogous to the urea cycle
Ring closure Tetrahydrofolate donates a second formyl group
De novo pyrimidine synthesis The pyrimidine base is synthesised before being attached to ribose
purines pyrimidines Basesynthesis on ribose free Amino acids gln(2), asp, asp gly Other molecules formate(2) carbamoyl HCO3- phosphate ATP 5 2 (UMP) (AMP,GMP) Comparison of purine and pyrimidine biosynthesis CMP gln 3
Ribonucleotides are used as precursors for deoxyribonucleotides ATP dATP GTP dGTP CTP dCTP UTP dUTP Ribonucleotide reductase
Thymidine nucleotides are derived from dUMP Tetrahydrofolate donates a methyl group
Degradation of pyrimidine nucleotides CTP UTP b-alanine, NH3, CO2
ATP ADP + Pi 2ADP ATP + AMP AMP IMP + NH4+ AMP deaminase Free ammonia is also produced in muscle • during severe muscle activity
GOUT • uric acid is quite insoluble • excess uric acid can crystallise in joints • gout can be treated with allopurinol • allopurinol is a competitive inhibitor of xanthine oxidase
The take home message • nucleotides have a number of functions • they can be synthesised de novo if required • some steps are analogous with the urea cycle • amino acids provide many of the components • synthesis is regulated by the concentrations of various nucleotides • synthesis is energetically expensive • the degradation of excess purines can cause gout