Hóa sinh Axit Nucleic

Page 1 Name of presentation by Mr X Nucleotide Metabolism Part II Lecturer: MARIA MILAGROS U. MAGAT, MD,MEM,FPPS,FPAPP Page 2 1. Nomenclature and structure of nucleotides 2. Nucleotide synthesis : De Novo and salvage pathways 3. Degradation of nucleotides 4. Clinical correlation OBJECTIVES: Page 3 PRPP SYNTHETASE OH CH 2 O OH OH 1 ’ 2 ’ 3 ’ 4 ’ 5 ’ H H PO 4 P PP RIBOSE 5 - PHOSPHATE 5 – PHOSPHORIBOSYL – 1- PYROPHOSPHATE PRPP SYNTHESIS – PRPP Page 4 CH 2 O OH OH 1 ’ 2 ’ 3 ’ 4 ’ 5 ’ H H PO 4 PP glutamine Glu phosphoribosyl amidotransferase OH CH 2 O 1 ’ 2 ’ 3 ’ 4 ’ 5 ’ H P HO NH 2 SYNTHESIS – P-ribose-NH 2 Page 5 Glycine Glutamine N 5 N 10 – methenyl tetrahydrofolate PRPP N 8 3 2 1 6 5 4 7 9 DE NOVO SYNTHESIS - PURINE PP H 2 CH C C N H OH CH 2 O 1 ’ 2 ’ 3 ’ 4 ’ 5 ’ H P HO H 2 H ATP Glutamine NH ATP ATP CO 2 OOC Aspartate ATP HN C O N 10 – Formyl tetrahydrofolate HC INOSINE MONOPHOSPHATE Page 6 Glycine DE NOVO SYNTHESIS Glutamine CO 2 Aspartate N 10 – Formyltetrahydrofolate INOSINE MONOPHOSPHATE Glutamine N 5 N 10 – methenyl tetrahydrofolate N 8 3 2 1 6 5 4 7 9 H 2 CH C C N H OH CH 2 1 ’ 2 ’ 3 ’ 4 ’ 5 ’ H P HO H N HN C O HC O ATP ATP ATP ATP Page 7 DE NOVO SYNTHESIS REACTION PRODUCT ENZYME Addition of imidazole ring 5 – phosphoribosylamine Glutamine PRPP amidotransferase Amide bond formation Glycinamide ribonucleotide GAR synthetase Formyl group transfer Formylglycinamide ribonucleotide GAR transformylase Amino group transfer Formylglycinamidine ribonucleotide FGAR amidotransferase Imidazole ring closure 5-aminoimidazole ribonucleotide FGAM cyclase Carboxylation of HCO 3 4–carboxy-5-aminoimidazole ribonucleotide AIR Carboxylase Amide group transfer SAICAR SAICAR synthetase Release of fumarate AICAR SAICAR Lyase Formyl transfer FAICAR AICAR transformylase Ring closure INOSINE MONOPHOSPHATE IMP synthetase Page 8 H PO 4 N N N N C C C C C H INOSINE MONOPHOSPHATE IMP DEHYDROGENASE O NAD XANTHYLATEGUANYLATE Glutamine O P PP H 2 N GMP SYNTHETASE DE NOVO SYNTHESIS - GMP Page 9 PO 4 N N N N C C HC CH C INOSINE MONOPHOSPHATE ADENYLOSUCCINATE LYASE ADENYLOSUCCINATEADENYLATE Aspartate O P ADENYLOSUCCINATE SYNTHETASE DE NOVO SYNTHESIS - AMP P P G H 2 N Fumarate Page 10 RECIPROCAL SUBSTRATE EFFECT IMP XANTHYLATE GUANYLATE ADENYLOSUCCINATE ADENYLATE ATP GTP Glutamine AMP GDP Aspartate CH O H 2 N N HN C C C N N C PO 4 CH H 2 N N HN C C C N N C PO 4