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乙醛介导的大鼠肝脏转氨酶抑制机制的研究。

Studies on the mechanism of acetaldehyde-mediated inhibition of rat liver transaminases.

作者信息

Solomon L R

机构信息

Department of Medicine, Veterans Administration Medical Center, West Haven, CT 06516.

出版信息

Clin Chim Acta. 1987 Sep 30;168(2):207-17. doi: 10.1016/0009-8981(87)90290-7.

DOI:10.1016/0009-8981(87)90290-7
PMID:3677417
Abstract

Incubation of mitochondria-depleted rat liver homogenates with 5 mmol/l acetaldehyde at 37 degrees C for 1 h inhibited both aspartate and alanine aminotransferases by 30%. Inhibition was prevented by decreasing temperature to 4 degrees C or by preincubating homogenates with cyanate but was unaffected by cyanamide and methylpyrazole which block acetaldehyde oxidation and reduction respectively. Cyanate-sensitive acetaldehyde-mediated inhibition of purified porcine heart transaminases was also demonstrated in the presence of rat liver homogenate but not in Tris/sucrose medium. Moreover, porcine transaminases were inhibited by trichloroacetic acid extracts of rat liver homogenates previously incubated with acetaldehyde but not by extracts of homogenates incubated with both acetaldehyde and cyanate. These findings suggest that acetaldehyde-mediated transaminase inhibition requires further non-oxidative metabolism of acetaldehyde. Since transaminase activities were not restored by addition of pyridoxal 5'-phosphate to the assay systems, acetaldehyde-induced transaminase inhibition does not appear to be mediated by displacement or depletion of this B6 coenzyme.

摘要

将线粒体缺失的大鼠肝脏匀浆与5 mmol/L乙醛在37℃孵育1小时,会使天冬氨酸转氨酶和丙氨酸转氨酶活性均降低30%。将温度降至4℃或预先用氰酸盐孵育匀浆可防止这种抑制作用,但分别阻断乙醛氧化和还原的氰胺和甲基吡唑对其没有影响。在大鼠肝脏匀浆存在的情况下,也证实了氰酸盐敏感的乙醛介导的对纯化猪心脏转氨酶的抑制作用,但在Tris/蔗糖培养基中则未观察到。此外,猪转氨酶被先前与乙醛孵育的大鼠肝脏匀浆的三氯乙酸提取物所抑制,但未被同时与乙醛和氰酸盐孵育的匀浆提取物所抑制。这些发现表明,乙醛介导的转氨酶抑制作用需要乙醛进一步的非氧化代谢。由于向测定系统中添加5'-磷酸吡哆醛并不能恢复转氨酶活性,因此乙醛诱导的转氨酶抑制作用似乎不是由这种B6辅酶的置换或消耗介导的。

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