Selective Uridine Triphosphate Deficiency Induced by d-Galactosamine in Liver and Reversed by Pyrimidine Nucleotide Precursors
Year: 1974
Type: article
Abstract: 1. d-Galactosamine induces a selective deficiency of UTP without reducing the pools of ATP, GTP, or CTP. This has been shown by means of enzymatic analyses in freeze-clamped rat livers and confirmed by column chromatography. 2. UDP-amino sugars derived from galactosamine increase by 0.85 µmole per g of liver while the UTP content drops from 0.26 to 0.02 µmole per g during 30 min after injection of d-galactosamine in a dose of 1.85 mmoles per kg of body weight. 3. Pyrimidine nucleotide precursors administered intraperitoneally in a dose of 4 mmoles per kg of body weight increase the sum of acid-soluble uracil nucleotides in liver during 1 hour to the following percentages as compared to the control value of 1.24 µmoles per g (100%): uridine, 210%; orotate, 144%; ureidosuccinate, 120%; carbamylphosphate, 122%. Uridine is also the most efficient precursor to increase the pool sizes of UTP, UDP, and UMP rapidly. 4. d-Galactosamine-induced UTP deficiency is reversed completely within 90 min after uridine administration. This offers the possibility to inhibit UTP-dependent processes in vivo for periods corresponding to the time interval between galactosamine and uridine injection. 5. RNA synthesis, as measured by incorporation of [14C]-guanosine into liver RNA, is depressed to 21% of the controls when the UTP content is reduced to 0.02 µmole per g of liver. Uridine promptly reverses this inhibition of RNA synthesis. 6. Depression of the concentration of UTP as substrate for RNA polymerases and its reversal by uridine provides a new means to inhibit RNA synthesis in vivo for defined time periods.
Source: Journal of Biological Chemistry
Institution: University of Freiburg
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,430
OpenAlex ID: W1500887326