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Depletion of cytidine triphosphate as a consequence of cellular uridine triphosphate deficiency
Author(s) -
Henninger Hanspeter,
Holstege Axel,
Herrmann Brigitte,
Anukarahata Tongtavuch,
Keppler Dietrich O.R.
Publication year - 1979
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(79)81273-9
Subject(s) - philosophy , physics , theology
The synthesis of CTP from UTP, catalyzed by CTP synthetase (EC 6.3.4.2), would imply that severe UTP deficiency causes a reduction of cellular CTP synthesis followed by a decrease in CTP pools. By contrast, UTP depletion induced by D-galactosamine in rat liver in vivo has been shown to be associated with a 2-fold increase in the hepatic content of CTP [ 1,2]. This result is confirmed in the present communication by means of high-pressure liquid chromatography of hepatic nucleotides. In vivo, the cytidine present in plasma [3] can contribute significantly to the synthesis of CTP on the salvage pathway. We have therefore studied hepatoma cell suspensions in vitro in order to evaluate the influence of the cellular level of UTP on CTP pools in the absence of extracellular cytidine. Under this condition a close correlation over a wide range was demonstrated between UTP and CTP contents. This correlation was independent from the agents used to induce UTP deficiency. These included inhibitors of de novo pyrimidine nucleotide synthesis and the uridylate-trapping amino sugars D-glucosamine (GlcN) and D-galactosamine (GalN). The analysis of pyrimidine nucleotides by highpressure liquid chromatography has shown an excellent agreement with our earlier enzymatic measurements ]4,51.