THE HIGHEST LEVELS OF PURINE CATABOLIC ENZYMES IN MICE ARE PRESENT INTHE PROXIMAL SMALL-INTESTINE

Recent studies on the tissue distribution and developmental regulation of adenosine deaminase (ADA) activity in mice show that very high ADA levels exist in the murine alimentary tract (tongue, esophagus, fores tomach, proximal small intestine) and at the fetal-maternal interface. To understand the role of ADA in these tissues, we measured the level s of three other enzymes involved in purine catabolism, purine nucleos ide phosphorylase (PNP), guanine deaminase (GDA), and xanthine dehydro genase (XDH), to see how their levels correlated with ADA activity. Ou r results show that the highest level of PNP, GDA, and XDH is present in the proximal small intestine. Levels of these purine catabolic enzy mes are much lower in the tongue, esophagus, forestomach, and fetal-ma ternal interface in marked contrast to ADA distribution. We also deter mined mRNA levels encoding PNP, XDH, and ADA in a variety of tissues. Tissue-specific differences in PNP, XDH, and ADA activity correlated w ith RNA abundance, indicating that the regulation of gene expression i s at the level of mRNA production. Thus, ADA is part of a purine catab olic pathway leading to the production of uric acid that is present at the highest known level in the proximal small intestine. ADA may have additional roles in other tissues.