The highest levels of purine catabolic enzymes in mice are present in the 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, 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.
Mohamedali
K A
KA
Department of Biochemistry and Cell Biology, Rice University, Houston, Texas 77005.
Guicherit
O M
OM
Kellems
R E
RE
Rudolph
F B
FB
D000243:Adenosine Deaminase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015870:Gene Expression; D006148:Guanine Deaminase / Q000235:genetics / Q000378:metabolism*; D007421:Intestine, Small / Q000201:enzymology*; D051379:Mice; D011683:Purine-Nucleoside Phosphorylase / Q000235:genetics / Q000378:metabolism*; D011687:Purines / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D014527:Uric Acid / Q000378:metabolism; D014968:Xanthine Dehydrogenase / Q000235:genetics / Q000378:metabolism*
D011687:Purines; D012333:RNA, Messenger; D014527:Uric Acid; D014968:Xanthine Dehydrogenase; D011683:Purine-Nucleoside Phosphorylase; D006148:Guanine Deaminase; D000243:Adenosine Deaminase