10-10-1+NA+Metabolism课件.pptVIP

The metabolic origin of the nine atoms in the purine ring system Salvage Pathway for Purines Hypoxanthine or Guanine + PRPP = IMP or GMP + PPi Hypoxanthineguanosylphosphoribosyl transferase (HGPRTase) Adenine + PRPP = AMP + PPi Adeninephosphoribosyl transferase (APRTase) (B) phosphoribosyl transferase (A) Pu 嘌呤核苷 嘌呤核苷酸 R-1-P Pi ATP ADP 嘌呤补救途径（salvage pathway of purine） (adenine phosohoribosyl transferase) (hypoxanthine-guanine phosohoribosyl transferase) 节约能量和一些氨基酸的消耗。 有些组织（如脑、骨髓）不能从头合成嘌呤核苷酸，只能进行嘌呤核苷酸的补救合成。 HGPRT完全缺失的患儿，表现为自毁容貌综合症。 嘌呤核苷酸补救合成的生理意义 Lesch-Nyhan Syndrome Absence of HGPRTase X-linked (Gene on X) Occurs primarily in males Characterized by: Increased uric acid Spasticity Neurological defects Aggressive behavior Self-mutilation Biosynthesis of Pyrimidines Pyrimidine rings are synthesized independent of the ribose and transferred to the PRPP (ribose) Generated as UMP (uridine 5’-monophosphate) Synthesized from: Glutamine CO2 Aspartic acid Requires ATP Uracil Cytosine The pyrimidine biosynthetic pathway (乳清酸) (二氢乳清酸) (乳清苷-5’-P) (氨甲酰天冬氨酸) (氨甲酰磷酸) Biosynthesis of Pyrimidines (乳清酸) (二氢乳清酸) (乳清酸苷-5’-P) (氨甲酰天冬氨酸) (天冬氨酸转氨甲酰基酶) (二氢乳清酸酶) (二氢乳清酸脱氢酶) (乳清酸磷酸核糖基转移酶) (乳清苷酸脱羧酶) (胞苷酸合成酶) (天冬氨酸转氨甲酰基酶) (二氢乳清酸酶) (二氢乳清酸脱氢酶) (乳清酸磷酸核糖基转移酶) (氨甲酰天冬氨酸) (二氢乳清酸) (乳清酸) (乳清酸苷-5’-P) (乳清苷酸脱羧酶) (胞苷酸合成酶) Regulation of Pyrimidine Biosynthesis Regulation occurs at first step in the pathway (committed step) 2ATP + CO2 + Glutamine = carbamoyl phosphate Inhibited by UTP If you have lots of UTP around this means you won’t make more that you don’t need X Hereditary Orotic Aciduria Defect in de novo synthesis of pyrimidines Loss of functional UMP synthetase Gene located on chromosome III Characterized by excretion of orotic acid Results in severe anemia and growth retardation Extremely rare (15 cases worldwide) Treated by feeding UMP Disease (-UMP) No UMP/excess orotate Disease (+UMP) Restore depleted UMP Downregulate pathway via feedback inhibition (Le