Schaller 2024 Lecture 35 Tutorial PDF

Base, nucleosides and nucleotides Adenine is a nitrogenous base, specifically a purine A nucleoside contains a A nucleotide is a nucleoside that contains nitrogenous base, e.g. adenine, phosphate groups on the sugar....

Base, nucleosides and nucleotides Adenine is a nitrogenous base, specifically a purine A nucleoside contains a A nucleotide is a nucleoside that contains nitrogenous base, e.g. adenine, phosphate groups on the sugar. covalently attached to a sugar, This is adenosine-5’-monophosphate (AMP). e.g. ribose. This is adenosine. Note the numbering of the sugar and the base. De novo synthesis of purine nucleotides Ribose-5-phosphate, product of the pentose phosphate pathway, is converted to PRPP, which is used in both de novo and salvage synthesis pathways. glycine The purine base is then synthesized on CO2 the C1 position of the sugar. aspartate The purine base is synthesized using atoms From glutamine, THF, glycine, aspartate and N10-formyl-THF CO2 N10-formyl-THF The circled nitrogen is covalently attached formate glutamine glutamine To C1 of the sugar in the first step of synthesis. FIGURE 28 Origin formate of Purine Ring Atoms IMP is the first purine nucleotide made. IMP is modified to make AMP and GMP.  Pyrimidine synthesis – de novo pathway PRPP is the sugar substrate for de novo synthesis of pyrimidine nucleotides (like purine nucleotide synthesis) Unlike de novo purine nucleotide synthesis, the pyrimidine ring is synthesized first and is then attached to PRPP Aspartate NH2 Carbamoyl phosphate synthetase II catalyzes the formation of carbamoyl C O phosphate from HCO3-, ATP and O glutamine PO32- Carbamoyl Carbamoyl phosphate and aspartate are phosphate covalently attached, cyclized and modified to generate orotate Orotate is covalently linked to PRPP to make OMP, which is modified to make UMP and CMP Salvage pathway for purine nucleotide synthesis Mutations in HGPRT cause Lesch-Nyhan De novo synthesis of nucleotides is Syndrome energetically costly. Another pathway recycles purines so they don’t always need to be made from scratch. Degradation of nucleotides can release nitrogenous bases, e.g. guanine. PRPP is also used in the salvage pathway. Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) – catalyzes the covalent linkage of guanine to PRPP to generate guanosine-5’-monophosphate