布氏布氏锥虫S-腺苷-L-甲硫氨酸脱羧酶的特性及其被贝尼尔、喷他脒和甲基乙二醛双（脒腙）抑制的情况
Characterization of Trypanosoma brucei brucei S-adenosyl-L-methionine decarboxylase and its inhibition by Berenil, pentamidine and methylglyoxal bis(guanylhydrazone).
作者信息
Bitonti A J, Dumont J A, McCann P P
出版信息
Biochem J. 1986 Aug 1;237(3):685-9. doi: 10.1042/bj2370685.
Abstract
Trypanosoma brucei brucei S-adenosyl-L-methionine (AdoMet) decarboxylase was found to be relatively insensitive to activation by putrescine as compared with the mammalian enzyme, being stimulated by only 50% over a 10,000-fold range of putrescine concentrations. The enzyme was not stimulated by up to 10 mM-Mg2+. The Km for AdoMet was 30 microM, similar to that of other eukaryotic AdoMet decarboxylases. T.b. brucei AdoMet decarboxylase activity was apparently irreversibly inhibited in vitro by Berenil and reversibly by pentamidine and methylglyoxal bis(guanylhydrazone). Berenil also inhibited trypanosomal AdoMet decarboxylase by 70% within 4 h after administration to infected rats and markedly increased the concentration of putrescine in trypanosomes that were exposed to the drug in vivo. Spermidine and spermine blocked the curative effect of Berenil on model mouse T.b. brucei infections. This effect of the polyamines was probably not due to reversal of Berenil's inhibitory effects on the AdoMet decarboxylase.
摘要
与哺乳动物的酶相比，布氏布氏锥虫的S-腺苷-L-甲硫氨酸（AdoMet）脱羧酶对腐胺激活相对不敏感，在10000倍的腐胺浓度范围内仅被刺激50%。该酶在高达10 mM的Mg2+存在下也不受刺激。AdoMet的Km为30 microM，与其他真核生物的AdoMet脱羧酶相似。布氏布氏锥虫的AdoMet脱羧酶活性在体外明显被贝尼尔不可逆抑制，被喷他脒和甲基乙二醛双（脒腙）可逆抑制。给感染大鼠给药后4小时内，贝尼尔还将锥虫体内的AdoMet脱羧酶抑制了70%，并显著提高了体内接触该药物的锥虫体内腐胺的浓度。亚精胺和精胺阻断了贝尼尔对模型小鼠布氏布氏锥虫感染的治疗效果。多胺的这种作用可能不是由于逆转了贝尼尔对AdoMet脱羧酶的抑制作用。
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