ATP depletion as a consequence of adenosine deaminase inhibition in man.
ATP depletion as a consequence of adenosine deaminase inhibition in man.
复制标题
人类腺苷脱氨酶抑制导致 ATP 耗竭。
DOI：
10.1073/pnas.77.10.6157
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发表时间：
1980
影响因子：
11.1
通讯作者：
Hutton,JJ
中科院分区：
文献类型：
--
作者：
Siaw,MF;Mitchell,BS;Koller,CA;Coleman,MS;Hutton,JJ
腺苷脱氨酶（腺苷氨基水解酶，EC 3.5.4.4）的遗传性缺乏导致以循环淋巴细胞显著减少为特征的免疫缺陷综合征。我们给一个淋巴组织增生性恶性肿瘤病人服用了腺苷脱氨酶的有效抑制剂2 '-脱氧共形霉素。腺苷脱氨酶活性的药物抑制的临床后果包括淋巴细胞计数突然减少、肾和肝功能异常以及溶血性贫血。腺苷和脱氧腺苷的血浆浓度分别上升到13 μ M和5 μ M的峰值，红细胞dATP水平在9天内增加到110 pmol/10（6）个细胞。红细胞ATP水平从128 pmol/10（6）细胞相应降低至< 6 pmol/10（6）细胞。第二名患者的红细胞中也出现了类似的ATP严重减少。与dATP积累相关的ATP的快速和意外消耗可能至少部分地解释了与2 '-脱氧共形霉素施用相关的毒性。ATP和dATP的反比关系提出了关于红细胞能量代谢控制的主要问题。
Hereditary deficiency of the enzyme adenosie deaminase (adenosine aminohydrolase, EC 3.5.4.4) results in an immunodeficiency syndrome characterized by a marked reduction in circulating lymphocytes. We have administered 2'-deoxycoformycin, a potent inhibitor of adenosine deaminase, to a patient with a lymphoproliferative malignancy. The clinical consequences of pharmacologic inhibition of adenosine deaminase activity included an abrupt decrease in the lymphocyte count, abnormalities of renal and hepatic function, and hemolytic anemia. The plasma concentrations of adenosine and deoxyadenosine rose to peak values of 13 microM and 5 microM, respectively, and erythrocyte dATP levels increased to 110 pmol/10(6) cells over 9 days. There was a corresponding decrease in erythrocyte ATP levels from 128 to < 6 pmol/10(6) cells. A similar profound reductin in ATP occurred in the erythrocytes of a second patient. The rapid and unexpected depletion of ATP associated with dATP accumulation may account, at least in part, for the toxicity associated with 2'-deoxycoformycin administration. The inverse relationship of ATP and dATP raises major questions about the control of energy metabolism in erythrocytes.