Abnormalities in S-adenosylhomocysteine hydrolysis, ATP catabolism, and lymphoid differentiation in adenosine deaminase deficiency.
Abnormalities in S-adenosylhomocysteine hydrolysis, ATP catabolism, and lymphoid differentiation in adenosine deaminase deficiency.
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腺苷脱氨酶缺乏症导致 S-腺苷同型半胱氨酸水解、ATP 分解代谢和淋巴分化异常。
DOI：
10.1111/j.1749-6632.1985.tb27098.x
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发表时间：
1985
影响因子：
5.2
通讯作者：
Schiff,R
中科院分区：
文献类型：
--
作者：
Hershfield,MS;Kurtzberg,J;Aiyar,VN;Suh,EJ;Schiff,R
Giblett和她的合作者发现了腺苷脱氨酶(ADA)和嘌呤核苷磷酸化酶(PNP)缺陷与选择性免疫缺陷疾病之间的联系，这一发现向生物化学家和免疫学家提出了具有挑战性的问题。这些酶缺乏的生化后果是什么？它们是如何导致选择性免疫功能障碍的？嘌呤代谢有没有调节免疫系统正常发育、活性或功能的特定方式？ADA和PNP缺乏症的生化后果清单即使不是完全的，也是广泛的。这些影响中的一些或全部导致选择性淋巴细胞减少的方式尚不清楚。在过去的几年里，我们的大部分研究都涉及确定腺苷脱氨酶的嘌呤核苷底物的生化效应。特别研究了腺苷(ADO)和脱氧腺苷(DAO)对S同型半胱氨酸水解酶的影响，对DAO诱导的dATP库扩大的调节，以及dATP引起的ATP耗竭的机制。我们最初的工作是用ADA抑制剂9-红血球-(2-羟基-3-壬基)腺嘌呤(EHNA)或脱氧辅酶A(DO)处理培养的人淋巴样细胞系。我们已经将我们的体外观察扩展到在杜克大学医学中心诊断为ADA和PNP缺乏症的几个儿童的体内情况。我们还通过深入研究T细胞白血病患者在接受DCF治疗期间急性ADA缺乏的生化和生物学后果，获得了有用和耐人寻味的信息。我想简要回顾一下我们在ADHcy代谢方面的工作，并描述一些关于ADA缺陷儿童的研究，这些研究主要与dATP Acc-1的影响有关。
The discoveries by Giblett and her collaborators of the associations between deficiencies of adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) and selective immunodeficiency diseases','have posed challenging questions to biochemists and immunologists. What are the biochemical consequences of these enzyme deficiencies and how do they lead to selective immune dysfunction? Are there specific ways in which purine metabolism regulates normal development, viability, or function of the immune system? The list of biochemical consequences of ADA and to a lesser degree PNP deficiency is, if not complete, extensive.'The manner in which some or all of these effects lead to selective lymphopenia is not yet clear. Most of our research of the past several years has dealt with defining the biochemical effects of the purine nucleoside substrates of adenosine deaminase. In particular we have examined the effects of adenosine (Ado) and deoxyadenosine (dAdo) on the enzyme S-adenosylhomocysteine (AdoHcy) hydrolase, the regulation of dAdoinduced dATP pool expansion, and the mechanism of dATP-induced ATP depletion. Our initial work was conducted with cultured human lymphoid cell lines treated with the ADA inhibitors 9-erythro-(2-hydroxy-3-nonyl) adenine (EHNA) or deoxycoformycin (do. We have extended our in vitro observations to the in vivo situation in studies of several children with ADA and PNP deficiency whom we have diagnosed at Duke University Medical Center. We have also obtained useful and intriguing information by studying in depth the biochemical and biological consequences of acute ADA deficiency in patients with T cell leukemias during their treatment with dCF. I would like to briefly review our work on AdoHcy metabolism and describe some studies of an ADA-deficient child that relate primarily to the effect of dATP accu-