Purine Catabolism in Isolated Hepatocytes : Influence of Coformycin
The nucleoside antibiotic coformycin1, a potent inhibitor of adenosine deaminase, has also been shown to interact with purified muscle AMP deaminase2. in rat liver extracts, maximal inhibition of adenosine deaminase and of AMP deaminase was observed with 10-7M and 5 × 10-5M coformycin respectively. In isolated rat hepatocytes the basal production of allantoin (30–40 nmol/min/g of cells) was not influenced by the addition of 10-7M coformycin, whereas the metabolization of adenosine was strongly inhibited. In hepatocytes in which the adenine nucleotide pool had been prelabelled with 14C adenine, 5 × 10-5M coformycin caused a 85 % inhibition of the basal production of allantoin and a complete suppression of the incorporation of 14C in the end products of purine catabolism.
KeywordsUric Acid Complete Suppression Adenine Nucleotide Maximal Inhibition Adenosine Triphosphate
- 1.T. Sawa, Y. Fukagawa, H. Homma, T. Takeuchi and H. Umezawa, Mode of action of coformycin on adenosine deaminase, J. Antibiot., Ser. A. 20:227–231 (1967).Google Scholar
- 2.R.P. Agarwal and R.E. Parks Jr., Potent inhibition of muscle 5′-AMP deaminase by the nucleoside antibiotics coformycin and deoxycoformycin, Biochem. Pharmacol. 26:663–666 (1977).Google Scholar
- 4.G. Van den Berghe, Ch. van Pottelsberghe and H.G. Hers, A kinetic study of the soluble 5′-nucleotidase of rat liver. Biochem. J. 162:611–616 (1977).Google Scholar