Helland S, Ueland P M
Cancer Res. 1983 Apr;43(4):1847-50.
The S-adenosylhomocysteine (AdoHcy) hydrolase (EC 3.3.1.1) activity and the metabolism of AdoHcy were investigated in various tissues of mice given a single injection or repetitive injections of 9-beta-D-arabinofuranosyladenine (ara-A) with and without the adenosine deaminase inhibitor, 2'-deoxycoformycin (dCF). A single injection of ara-A (50 mg/kg) rapidly inactivated AdoHcy hydrolase in several organs (liver, kidney, spleen, lung, heart, skeletal muscle, and brain). Then, the enzyme activity in these tissues gradually recovered. This process, termed reactivation of AdoHcy hydrolase, was not sensitive to cycloheximide but was partly inhibited by dCF. In the absence of dCF, nearly no increase in AdoHcy content in the tissues was observed, whereas a single injection of ara-A plus dCF induced a small, transient increase in AdoHcy content of most tissues. Repetitive injections of ara-A (without dCF) caused a moderate increase in the AdoHcy level of tissues, whereas repetitive injections of the drug combination ara-A plus dCF resulted in a massive accumulation of AdoHcy in liver and kidney and, to a lesser degree, in other tissues. A moderate increase in S-adenosyl-L-methionine was observed in some tissues. These metabolic effects were associated with a rapid inactivation of AdoHcy hydrolase, but a fraction of the enzyme activity (about 8% in liver) was not or only slowly inactivated. AdoHcy accumulated in serum of mice receiving this treatment. Treatment of mice with dCF alone for up to 10 hr induced no increase in AdoHcy content of the tissues.
在给小鼠单次注射或重复注射9-β-D-阿拉伯呋喃糖基腺嘌呤（ara-A），同时给予或不给予腺苷脱氨酶抑制剂2'-脱氧助间型霉素（dCF）的情况下，研究了S-腺苷同型半胱氨酸（AdoHcy）水解酶（EC 3.3.1.1）的活性以及AdoHcy的代谢情况。单次注射ara-A（50 mg/kg）可迅速使多个器官（肝脏、肾脏、脾脏、肺、心脏、骨骼肌和脑）中的AdoHcy水解酶失活。然后，这些组织中的酶活性逐渐恢复。这一过程称为AdoHcy水解酶的再激活，对环己酰亚胺不敏感，但部分受到dCF的抑制。在没有dCF的情况下，未观察到组织中AdoHcy含量有明显增加，而单次注射ara-A加dCF会导致大多数组织中AdoHcy含量出现小幅度的短暂增加。重复注射ara-A（不使用dCF）会使组织中的AdoHcy水平适度升高，而重复注射ara-A加dCF的药物组合会导致肝脏和肾脏中AdoHcy大量蓄积，其他组织中蓄积程度较轻。在一些组织中观察到S-腺苷-L-甲硫氨酸有适度增加。这些代谢效应与AdoHcy水解酶的快速失活有关，但仍有一部分酶活性（肝脏中约8%）未失活或仅缓慢失活。接受该治疗的小鼠血清中AdoHcy蓄积。单独用dCF处理小鼠长达10小时，未导致组织中AdoHcy含量增加。
