Production of adenosine and nucleoside analogs by the exchange reaction catalyzed by rat liver adenosine kinase.
We have previously shown [8] that rat liver adenosine kinase can produce [14C]AMP from [14C]adenosine (Ado) and unlabelled adenosine monophosphate (AMP), in the absence of ATP, by an exchange reaction. In this study, we investigated whether Ado or AMP could be replaced in this exchange reaction by other nucleosides or nucleoside monophosphates (NMP), respectively. In the presence of 1 mM of the unlabelled NMP analogs 7-deazaadenosine (tubercidin) 5'-monophosphate, 6-chloropurine riboside 5'-monophosphate, or N6-methyl-AMP, [14C]AMP was formed from 20 microM [14C]Ado at up to 50% of the rate recorded with 1 mM unlabelled AMP. In the presence of 0.2 mM of the unlabelled analog nucleosides tubercidin, N6-methyladenosine, or 6-methylmercaptopurine riboside, [14C]Ado was generated from 1 mM [14C]AMP at up to 60% of the rate recorded with 0.2 mM unlabeled Ado. Small amounts of [14C]Ado were also formed from the natural nucleosides 5-amino-4-imidazolecarboxamide (AICA) riboside or 2'-deoxyadenosine. Administration of therapeutic anticancer and antiviral nucleosides that can serve as substrates for the exchange reaction catalyzed by adenosine kinase might, thus, result in a net production of Ado, a potent autacoid with physiological effects in numerous tissues.
Mimouni
M
M
Laboratory of Physiological Chemistry, University of Louvain Medical School, Brussels, Belgium.
Bontemps
F
F
Van den Berghe
G
G
D000241:Adenosine / Q000096:biosynthesis*; D000244:Adenosine Diphosphate / Q000378:metabolism / Q000494:pharmacology; D000248:Adenosine Kinase / Q000378:metabolism*; D000249:Adenosine Monophosphate / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D002250:Carbon Radioisotopes; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008297:Male; D009705:Nucleosides / Q000096:biosynthesis* / Q000378:metabolism / Q000494:pharmacology; D009711:Nucleotides / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D002250:Carbon Radioisotopes; D009705:Nucleosides; D009711:Nucleotides; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D000248:Adenosine Kinase; D000241:Adenosine