3 Nucleotides Synthsis and Degradation英文学习资料 .pptVIP

Biosynthesis and Degradation of Nucleotides Two types of pathway lead to nucleotides De novo synthesis of nucleotides begins with their metabolic precursors: amino acids, ribose 5-phosphate, NH3, and CO2. Salvage pathways recycle the free bases and nucleosides released from nucleic acid breakdown. The purine ring is assembled on ribose phosphate to make AMP and GMP; the pyrimidine ring is first synthesized as orotate, which is then attached to ribose phosphate before being converted to UTP and CTP. The deoxyribonucleotides (dNDPs) are synthesized by reduction of ribonucleotides (NDPs). Radioisotope tracer experiments revealed the origin of the atoms in the purine and pyrimidine rings Buchanan and Greenberg did this by feeding a variety of isotopically labeled compounds to pigeons (1940s). The atoms of the purine rings were found to be derived from formate, CO2, Gly, Asp, and Gln. The atoms of the pyrimidine rings were found to be derived from Asp, Gln and HCO3-. Contents De novo purine nucleotide synthesis De novo pyrimidine nucleotide synthesis Nucleoside monophoshates are converted to nucleoside triphosphates Ribonucleotides are the precursors of deoxy-ribonucleotides Degradation of purine and pyrimidine The salvage pathways for purine and pyrimidine Many chemotherapeutic agents target enzymes in the nucleotide biosynthetic pathways 1. De novo purine nucleotide synthesis The bases are not synthesized and then attached to ribose The purine ring is built up one or a few atoms at a time, attached to ribose throughout the process. The enzymes of IMP synthesis appear to be organized as large multienzyme complexes Steps 1, 3, and 5; steps 7 and 8; steps 10 and 11 are catalyzed by a multifunctional protein respectively in some eukaryotic cells. In bacteria, these activities are found on separate proteins, but a large noncovalent complex may exist in these cells. The biosynthesis of AMP and GMP is regulated by feedback inhibition Three major feedback mechanis