The highest levels of purine catabolic enzymes in mice are present in the proximal small intestine.

F.B Rudolph,O.M Guicherit,K.A Mohamedali,R.E Kellems

doi:10.1016/s0021-9258(19)49521-5

Abstract

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, forestomach, proximal small intestine) and at the fetal-maternal interface. To understand the role of ADA in these tissues, we measured the levels of three other enzymes involved in purine catabolism, purine nucleoside phosphorylase (PNP), guanine deaminase (GDA), and xanthine dehydrogenase (XDH), to see how their levels correlated with ADA activity. Our results show that the highest level of PNP, GDA, and XDH is present in the proximal small intestine. Levels of these purine catabolic enzymes are much lower in the tongue, esophagus, forestomach, and fetal-maternal interface in marked contrast to ADA distribution. We also determined mRNA levels encoding PNP, XDH, and ADA in a variety of tissues. Tissue-specific differences in PNP, XDH, and ADA activity correlated with RNA abundance, indicating that the regulation of gene expression is at the level of mRNA production. Thus, ADA is part of a purine catabolic 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.

Highlights

Recent studies on the tissue distribution and develoBpec-ause of the physiological importance ofADA it is not mental regulationof adenosine deaminase(ADA) activ- surprising that theenzyme is widely distributed in natureT. he ity in mice show that very hiAghDA levels existin the enzyme has been found in virtually all vertebratetissues, and murine alimentary tract and at the fetal-maternal among different tissues and within the same tissues from difinterface.To understand the roolef ADAin these tissues, ferent species (6,7).The most information i s known concerning we measured thleevelsof three other enzymes involvedthe cellular localization and developmental expression (8) of in purine catabolism, purine nucleoside phosphorylaseADA in mice
Our results indicate that each of these purine catabolic enzymes is found at its highest level in the proximal small intestine
We extended these findings by using purine nucleoside phosphorylase (PNP) and XDHcDNA probes to show that the highest mRNA levels for these enzymes is found in the small

Summary

Introduction

Recent studies on the tissue distribution and develoBpec-ause of the physiological importance ofADA it is not mental regulationof adenosine deaminase(ADA) activ- surprising that theenzyme is widely distributed in natureT. he ity in mice show that very hiAghDA levels existin the enzyme has been found in virtually all vertebratetissues, and murine alimentary tract (tongue, esophagus, forestom- it has been observed that the level ofADA varies markedly ach, proximal smallintestine) and at the fetal-maternal among different tissues and within the same tissues from difinterface.To understand the roolef ADAin these tissues, ferent species (6,7).The most information i s known concerning we measured thleevelsof three other enzymes involvedthe cellular localization and developmental expression (8) of in purine catabolism, purine nucleoside phosphorylaseADA in mice. PNP, GDA,and XDH is present in the proximal small The enzyme is most abundant in the keratinized squamous intestine.

Results

Conclusion