二十一核酸代谢.pptVIP

Nucleotide Metabolism Cellular Roles of Nucleotides Energy metabolism (ATP)* Monomeric units of nucleic acids* Regulation of physiological processes Adenosine controls coronary blood flow cAMP and cGMP serve as signaling molecules Precursor function-GTP to tetrahydrobiopterin Coenzyme components- 5’-AMP in FAD/NAD+ Activated intermediates- UDP Glucose Allosteric effectors- regulate themselves and others How I hope to make this at least bearable if not mildly interesting Purines and Pyrimidines Synthesis (de novo and salvage pathways) Degradation Relevant disease states Relevant clinical applications Purines and Pyrimidines Synthesis Pathways For both purines and pyrimidines there are two means of synthesis (often regulate one another) de novo (from bits and parts) salvage (recycle from pre-existing nucleotides) Many Steps Require an Activated Ribose Sugar (PRPP) de novo Synthesis Committed step: This is the point of no return Occurs early in the biosynthetic pathway Often regulated by final product (feedback inhibition) Purine Biosynthesis (de novo) Atoms derived from: Aspartic acid Glycine Glutamine CO2 Tetrahydrofolate Also requires 4 ATPs Purine Biosynthesis (de novo) Salvage Pathway for Purines 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) Regulation of Pyrimidine Biosynthesis Regulation occurs at first step in the pathway (committed step) 2ATP + CO2 + Glutamine = carbamoyl phosphate 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 b