Adenosine Metabolism, Adenosine Kinase, and Evolution

The enzyme adenosine kinase (AdK, ADK, or AK) plays an important role in regulating the intracellular as well as extracellular concentrations of adenosine and hence its diverse physiological actions. In view of the enormous pharmacological potential of adenosine, there has been much interest in studying adenosine kinase over the past few decades. This chapter summarizes the wealth of information that has accumulated concerning its structure and function. The aspects that are reviewed include the enzymological aspects of ADK including its reaction mechanism and ionic requirement; insights provided by the crystal structure of the enzyme; a brief overview of work on identification and development of ADK inhibitors; novel aspects of the ADK gene structure; tissue distribution and subcellular localization of the two ADK isoforms; novel information provided by mammalian cells harboring mutations of ADK; and lastly the evolutionary relationship of ADK to other related proteins. Despite enormous progress several important gaps exist in our knowledge regarding ADK, particularly concerning the cellular functions of the two isoforms and how their relative amounts in different tissues are regulated, that need to be understood in order to fully realize the therapeutic potential of increased local concentration of adenosine by modulation of this key enzyme.