Purine and pyrimidine catabolism

PURINE AND PYRIMIDINE CATABOLISM

PURINE CATABOLISM

PURINE DEGRADATION

PURINE SALVAGE PATHWAY From normal turnover of cellular nucleic

acids Obtained from the diet Reutilization of adenine, hypoxanthine,

and guanineTwo enzymes:

1. Adenine phosphoribosyltransferase2. Hypoxanthine-guanine phosphoribosyltransferase

Hypoxanthine

Xanthine

Xanthine dehydrogenase

Allopurinol

GOUT

•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

Lesch-Nyhan Syndrome

LESCH-NYHAN SYNDROME

PYRIMIDINE CATABOLISM

RIBONUCLEOTIDES TO DEOXYRIBONUCLEOTIDES

Very Important!

Guanine-Cytosine Adenine-Thymine

DNA Base Pairing

CHARGAFF’S RULE %A = %T and %G = %C In DNA, 1:1 ratio between purines and

pyrimidinesOrganism %A %G %C %T A/T G/C %GC %AT

φX174 24.0 23.3 21.5 31.2 0.77 1.08 44.8 55.2

Maize 26.8 22.8 23.2 27.2 0.99 0.98 46.1 54.0

Octopus 33.2 17.6 17.6 31.6 1.05 1.00 35.2 64.8

Chicken 28.0 22.0 21.6 28.4 0.99 1.02 43.7 56.4Rat 28.6 21.4 20.5 28.4 1.01 1.00 42.9 57.0

Human 29.3 20.7 20.0 30.0 0.98 1.04 40.7 59.3

Grasshopper

29.3 20.5 20.7 29.3 1.00 0.99 41.2 58.6

Sea Urchin 32.8 17.7 17.3 32.1 1.02 1.02 35.0 64.9

Wheat 27.3 22.7 22.8 27.1 1.01 1.00 45.5 54.4

Yeast 31.3 18.7 17.1 32.9 0.95 1.09 35.8 64.4

E. Coli 24.7 26.0 25.7 23.6 1.05 1.01 51.7 48.3

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