Effect of inhibition of polyamine synthesis on the content of decarboxylated S-adenosylmethionine.
Effect of inhibition of polyamine synthesis on the content of decarboxylated S-adenosylmethionine.
复制标题
抑制多胺合成对脱羧S-腺苷甲硫氨酸含量的影响。
DOI：
10.1042/bj2020519
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发表时间：
1982
期刊：
影响因子：
--
通讯作者：
Bennett,RA
中科院分区：
文献类型：
--
作者：
Pegg,AE;Pösö,H;Shuttleworth,K;Bennett,RA
1.用α-二氟甲基鸟氨酸抑制鸟氨酸脱羧酶后，转化的小鼠成纤维细胞(SV-3T3细胞)中脱羧腺苷甲硫氨酸(ADOMet)的含量增加了500倍，达到约0.4fmol/细胞。这是由于缺少腐胺和亚精胺作为氨丙基转移酶的底物，脱羧化的ADOMet作为氨丙基供体，以及亚精胺的耗尽导致ADOMet脱羧酶的活性增强。添加腐胺可消除脱羧基ADMet含量的增加，但1，3-二氨基丙烷不能。2.5‘-甲基硫代除草素可能通过直接抑制氨丙基转移酶的活性而增加脱羧基ADO-Met的含量，但其含量的增加和亚精胺含量的下降远小于α-二氟甲基鸟氨酸。3.用鸟氨酸脱羧酶抑制剂处理大鼠再生肝，测定肝组织脱羧基ADMet含量。对照组大鼠肝部分切除后32h，α-二氟甲基鸟氨酸使其含量增加60%，二氟甲基鸟氨酸增加90%，1，3-二氨基丙烷抑制腐胺和亚精胺合成增加330%。1，3-二氨基丙烷完全阻止了肝部分切除后精胺的增加，暴露48h后，肝脏脱羧基ADMet浓度增加了5倍。这些增加可以通过腐胺或甲基乙二醛双(鸟苷酸)，一种ADOMet脱羧酶的抑制剂来预防。4.这些结果表明，ADOMet代谢的改变是由于给予多胺合成的特异性抑制剂。在解释使用这种抑制剂获得的结果时，应考虑脱羧基ADMet积累的可能后果，例如，这可能会干扰正常的细胞甲基化或导致细胞腺嘌呤核苷酸的耗尽。
1. The content of decarboxylatedS-adenosylmethionine (AdoMet) in transformed mouse fibroblasts (SV-3T3 cells) was increased 500-fold to about 0.4fmol/cell when ornithine decarboxylase was inhibited by α-difluoromethylornithine. This increase was due to the absence of putrescine and spermidine, which serve as substrates for aminopropyltransferases with decarboxylated AdoMet as an aminopropyl donor, and to the enhanced activity of AdoMet decarboxylase brought about by depletion of spermidine. The increase in decarboxylated AdoMet content was abolished by addition of putrescine, but not by 1,3-diaminopropane. 2. 5′-Methylthiotubercidin also increased decarboxylated AdoMet content, presumably by direct inhibition of aminopropyl-transferase activities, but the increase in its content and the decline in spermidine content were much less than those produced by α-difluoromethylornithine. 3. Decarboxylated AdoMet content of regenerating rat liver was measured in rats treated with inhibitors of ornithine decarboxylase. The content was increased by 60% 32h after partial hepatectomy in control rats, by 90% when α-difluoromethylornithine was given to the partially hepatectomized rats, and by 330% when 1,3-diaminopropane was used to inhibit putrescine and spermidine synthesis. After 48h of exposure to 1,3-diaminopropane, which completely prevented the increase in spermidine after partial hepatectomy, there was a 5-fold rise in hepatic decarboxylated AdoMet concentration. These increases were prevented by treatment with putrescine or with methylglyoxal bis(guanylhydrazone), an inhibitor of AdoMet decarboxylase. 4. These results show that changes in AdoMet metabolism result from the administration of specific inhibitors of polyamine synthesis. The possible consequences of the accumulation of decarboxylated AdoMet, which could, for example, interfere with normal cellular methylation or lead to depletion of cellular adenine nucleotides, should be considered in the interpretation of results obtained with such inhibitors.