Purine and pyrimidine catabolism

1. Purine and pyrimidine catabolism

2. Purine catabolism

3. Purine degradation

4. Purine Salvage Pathway • From normal turnover of cellular nucleic acids • Obtained from the diet • Reutilization of adenine, hypoxanthine, and guanine • Two enzymes: • 1. Adenine phosphoribosyltransferase • 2. Hypoxanthine-guanine phosphoribosyltransferase

7. Hypoxanthine Xanthine dehydrogenase Xanthine Allopurinol

8. Gout

9. Lesch-Nyhan Syndrome • Build up of hypoxanthine and guanine • Degradation of hypoxanthine and guanine results in increased uric acid • Absence of Hypoxanthine-guanine phosphoribosyltransferase. • Excess uric acid in urine often results in orange crystals in the diaper of affected children • Severe mental retardation • Self-mutilation • Involuntary movements • Gout

10. Lesch-nyhan syndrome

11. Pyrimidine catabolism

14. Very Important! Ribonucleotides to Deoxyribonucleotides

16. DNA Base Pairing Guanine-Cytosine Adenine-Thymine

17. CharGaff’s Rule • %A = %T and %G = %C • In DNA, 1:1 ratio between purines and pyrimidines

18. Summary • Purines: Uric acid • Reutilization of adenine, hypoxanthine and guanine • End product: Urate (a.k.a.: Uric Acid ) • Altered metabolism: Gout • Pyrimidines: Citric acid intermediates • Acetyl-CoA derived from Cytosine and Uracil degradation; Propionyl-CoA (Succinoyl-CoA) from Thymine degradation • Ammonia and CO2 • Ring undergoes complete degradation