分子生物学英文课件：Chapter2 Metabolism of Nucleotides.ppt

Synthetic analogs of bases、 Nucleosides and nucleotides are used in chemotherapeutics and science research β-alanine + NH3 + CO2 Catabolism of pyrimidine nucleotides thymine dihydrothymine β -aminoisobutyrate NH3 + CO2 * Figure 22-45 dAMP dGMP Antimetabolites of purine nucleotides 1.Analog of purine : 6-mercaptopurine (6MP, 6MP nucleotides ) : hypoxanthine, IMP 2.Analog of amino acid: azaserine(重氮丝氨酸 )：glutamine 3.Analog of folic acid: aminopterin(氨基蝶呤 ), methotrexate (甲氨蝶呤 )： inhibit dihydrofolate reductase 6MP hypoxanthine azaserine glutamine folic acid aminopterin(氨基蝶呤 ), methotrexate (甲氨蝶呤 ) 6MP - MTX - - Adenylosuccinate synthase IMP dehydrogenase Lesch-Nyhan syndrome 6MP - Catabolism of purine nucleotides decreases uric acid formation： isomer of hypoxanthine (a naturally occurring purine in the body) , an inhibitor of the enzyme xanthine oxidase decreases purine synthesis ：causes an increase in allopurinol nucleotide(isomer of IMP), which can not only decrease PRPP, but also feedback inhibit amidophosphoribosyl transferase. Metabolism of pyrimidine nucleotides Metabolism of pyrimidine nucleotides Types of pyrimidine nucleotides: *UMP, CMP, dTMP, dUMP, dCMP *UDP, CDP, dTDP, dUDP, dCDP *UTP, CTP, dTTP, dUTP, dCTP Anabolism: *de novo synthesis *salvage pathway Catabolism de novo synthesis of pyrimidine nucleotides Precursors: Gln, Asp, CO2 , one-carbon unit(for T) and ribose-5-phosphate Location: liver Process: *UMP synthesis from the raw materials *CTP synthesis *formation of pyrimidine deoxyribonucleotides * TMP synthesis CO2 (CAP) (CAA) CPS-Ⅱ Aspartate carb- amoyl transferase CO2 CO2 The sources of the nitrogen and carbon atoms of the pyrimidine ring (CPS-Ⅰ) (CPS-Ⅱ) Gln+CO2 2 Synthesis of CTP One carbon unit (methylation) CH3 amido regulation of de novo synthesis of pyrimidine nucleotides Carbamoyl phosphate Carbamoyl as