Nikula P, Alhonen-Hongisto L, Jänne J
Biochem J. 1985 Oct 1;231(1):213-6. doi: 10.1042/bj2310213.
Derivatives of glyoxal bis(guanylhydrazone) (GBG), such as methylglyoxal bis(guanylhydrazone) and ethylglyoxal bis(guanylhydrazone), are potent inhibitors of S-adenosylmethionine decarboxylase (EC 4.1.1.50), the key enzyme required for the synthesis of spermidine and spermine. These compounds, but not the parent compound, induce a massive accumulation of putrescine, partly by blocking the conversion of putrescine into spermidine, but also by strikingly stimulating ornithine decarboxylase (ODC; EC 4.1.1.17) activity. The mechanism of the stimulation of ODC activity and enhanced accumulation of the enzyme protein apparently involved a distinct stabilization of the enzyme against intracellular degradation. However, although the parent compound GBG also stabilized ODC, it powerfully inhibited the enzyme activity and the accumulation of immunoreactive protein in cultured L1210 leukaemia cells. Kinetic considerations indicated that, in addition to the stabilization, all three compounds, GBG in particular, inhibited the expression of ODC. It is unlikely that the decreased rate of synthesis of ODC was attributable to almost unaltered amounts of mRNA in drug-treated cells, thus supporting the view that especially GBG apparently depressed the expression of ODC at some post-transcriptional level.
乙二醛双（脒腙）（GBG）的衍生物，如甲基乙二醛双（脒腙）和乙基乙二醛双（脒腙），是S-腺苷甲硫氨酸脱羧酶（EC 4.1.1.50）的强效抑制剂，而该酶是合成亚精胺和精胺所需的关键酶。这些化合物，而非母体化合物，会诱导腐胺大量积累，部分原因是阻断了腐胺向亚精胺的转化，但也因为显著刺激了鸟氨酸脱羧酶（ODC；EC 4.1.1.17）的活性。刺激ODC活性及增强该酶蛋白积累的机制显然涉及该酶对细胞内降解的独特稳定作用。然而，尽管母体化合物GBG也能稳定ODC，但它在培养的L1210白血病细胞中却强烈抑制该酶活性及免疫反应性蛋白的积累。动力学研究表明，除了稳定作用外，这三种化合物，尤其是GBG，还抑制ODC的表达。ODC合成速率降低不太可能归因于药物处理细胞中mRNA量几乎未变，因此支持了这样一种观点，即特别是GBG显然在转录后水平抑制了ODC的表达。
