Kinetic considerations for the regulation of adenosine and deoxyadenosine metabolism in mouse and human tissues based on a thymocyte model.
Metabolic regulation at a branch point may be determined primarily by relative enzyme activities and affinity for common substrate. Adenosine and deoxyadenosine are both phosphorylated and deaminated and their metabolism was studied in intact mouse thymocytes. From kinetic considerations of two activities competing for a common substrate, the deamination:phosphorylation ratio, vd/vk, at high nucleoside concentration, [S] congruent to infinity, is equal to Vd/Vk, or 34 and 1090 for adenosine and deoxyadenosine, respectively. At low substrate concentrations, [S] congruent to o, vd/vk is equal to VdKkm/VkKdm, or 0.7 and 285 for adenosine and deoxyadenosine, respectively. The analysis was extended to other mouse and human tissues by measurement of adenosine kinase, deoxyadenosine kinase and adenosine deaminase activities. All tissues were found to preferentially deaminate deoxyadenosine. Three tissue types were apparent with respect to adenosine metabolism: those which preferentially phosphorylate adenosine at all concentrations, those which switch from phosphorylation to deamination between low and high adenosine concentration and those for which deamination is quantatively important at all concentrations. Lymphoid tissues are representative of the latter category. The kinetic approach we describe offers a means of predicting nucleoside metabolism over a range of concentration which may be technically difficult to otherwise measure. The phosphorylation of adenosine and deoxyadenosine was also studied in intact thymocytes in the presence of adenosine deaminase inhibitors. The rate of deoxyadenosine phosphorylation was unaffected by coformycin or EHNA, whereas adenosine phosphorylation decreased with increasing substrate concentrations to 18% the rate in the absence of adenosine deaminase inhibitors.
D000241:Adenosine / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism; D003839:Deoxyadenosines / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000378:metabolism; D007700:Kinetics; D007962:Leukocytes / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism*; D051379:Mice; D009928:Organ Specificity; D013045:Species Specificity; D013154:Spleen / Q000378:metabolism; D013950:Thymus Gland / Q000378:metabolism*
D003839:Deoxyadenosines; D000241:Adenosine