Mohamedali K A, Guicherit O M, Kellems R E, Rudolph F B
Department of Biochemistry and Cell Biology, Rice University, Houston, Texas 77005.
J Biol Chem. 1993 Nov 5;268(31):23728-33.
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.
最近对小鼠体内腺苷脱氨酶（ADA）活性的组织分布和发育调控的研究表明，在小鼠的消化道（舌头、食道、前胃、近端小肠）以及胎儿与母体的界面处存在非常高的ADA水平。为了了解ADA在这些组织中的作用，我们测量了参与嘌呤分解代谢的其他三种酶的水平，即嘌呤核苷磷酸化酶（PNP）、鸟嘌呤脱氨酶（GDA）和黄嘌呤脱氢酶（XDH），以观察它们的水平与ADA活性之间的相关性。我们的结果表明，PNP、GDA和XDH的最高水平存在于近端小肠中。与ADA的分布形成鲜明对比的是，这些嘌呤分解代谢酶在舌头、食道、前胃和胎儿与母体界面处的水平要低得多。我们还测定了多种组织中编码PNP、XDH和ADA的mRNA水平。PNP、XDH和ADA活性的组织特异性差异与RNA丰度相关，表明基因表达的调控发生在mRNA产生的水平。因此，ADA是嘌呤分解代谢途径的一部分，该途径导致尿酸的产生，尿酸在近端小肠中的含量处于已知的最高水平。ADA可能在其他组织中具有额外的作用。
