S-Adenosylhomocysteine hydrolase as a target for intracellular adenosine action.
S-Adenosylhomocysteine hydrolase (AdoHcyase) controls intracellular levels of S-adenosylhomocysteine (AdoHcy). AdoHcy is a potent product inhibitor of some S-adenosylmethionine-dependent methyltransferases. Pharmacological modulation of AdoHcyase to indirectly inhibit methyltransferases can be guided by the fact that adenosine binds with high affinity to AdoHcyase and inhibits enzyme activity. cAMP can compete with adenosine and can counteract the adenosine-induced inhibition of AdoHcyase. Thus, the ratio between adenosine and cAMP, which can vary under different physiological conditions, might result in changes in, for example, DNA promoter methylation and therefore transcription.
Kloor
Doris
D
Department of Pharmacology and Toxicology, Faculty of Medicine, University of Tübingen, Wilhelmstrasse 56, D-72074 Tübingen, Germany. doris.kloor@uni-tuebingen.de
Osswald
Hartmut
H
D000241:Adenosine / Q000494:pharmacology*; D043383:Adenosylhomocysteinase / Q000187:drug effects*; D000818:Animals; D000242:Cyclic AMP / Q000502:physiology; D006801:Humans; D008958:Models, Molecular; D012435:S-Adenosylhomocysteine / Q000378:metabolism
D012435:S-Adenosylhomocysteine; D000242:Cyclic AMP; D043383:Adenosylhomocysteinase; D000241:Adenosine