11:115:301 Lecture Notes - Lecture 21: De Novo Synthesis, Phosphoribosyl Pyrophosphate, Dihydrofolate Reductase

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Treat with dhfr inhibitor (methotrexate) lots of copies of dhfr. Two pathways for the synthesis of nucleotides: de novo pathway (from scratch) Activated ribose (prpp) + amino acids + atp + Co2 + nucleotide: purine salvage pathway. If you don"t save purine accumulates gout. When cells turnover their dna don"t throw everything out. Ribonucleotide (base + sugar + phosphate) adenosine guanosine uridine cytidine. Deoxyribonucleotide deoxyadenosine deoxyadenylate deoxyguanosine deoxyguanylate thymidine thymidylate deoxycytidine deoxycytidylate adenine guanine uracil cytosine adenine guanine thymine cytosine. A brief description of the de-novo synthesis of purine. Framework for base is synthesized piece by piece directly onto ribose-based structure. Framework is assembled first then attached to ribose. Purine synthesis uses prpp as backbone. Ribose 5-phosphate + atp --prpp synthetase--> prpp. Product of purine synthesis = imp (inosine monophosphate) All purines come from imp or inosinate. Inosate = mix with rbc to nourish them. Deoxy-nucleotriphosphates are derived from ribo-nucleodiphosphates by ribonucleotide reductase.

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