Slocum R D, Bitonti A J, McCann P P, Feirer R P
Department of Biology, Williams College, Williamstown, MA 01267.
Biochem J. 1988 Oct 1;255(1):197-202. doi: 10.1042/bj2550197.
DL-alpha-Difluoromethylarginine (DFMA) is an enzyme-activated irreversible inhibitor of arginine decarboxylase (ADC) in vitro. DFMA has also been shown to inhibit ADC activities in a variety of plants and bacteria in vivo. However, we questioned the specificity of this inhibitor for ADC in tobacco ovary tissues, since ornithine decarboxylase (ODC) activity was strongly inhibited as well. We now show that [3,4-3H]DFMA is metabolized to DL-alpha-difluoromethyl[3,4-3H]ornithine [( 3,4-3H]DFMO), the analogous mechanism-based inhibitor of ODC, by tobacco tissues in vivo. Both tobacco and mammalian (mouse, bovine) arginases (EC 3.5.3.1) hydrolyse DFMA to DFMO in vitro, suggesting a role for this enzyme in mediating the indirect inhibition of ODC by DFMA in tobacco. These results suggest that DFMA may have other effects, in addition to the inhibition of ADC, in tissues containing high arginase activities. The recent development of potent agmatine-based ADC inhibitors should permit selective inhibition of ADC, rather than ODC, in such tissues, since agmatine is not a substrate for arginase.
DL-α-二氟甲基精氨酸（DFMA）在体外是精氨酸脱羧酶（ADC）的一种酶激活不可逆抑制剂。DFMA在体内也已被证明可抑制多种植物和细菌中的ADC活性。然而，我们对这种抑制剂在烟草子房组织中对ADC的特异性提出质疑，因为鸟氨酸脱羧酶（ODC）活性也受到了强烈抑制。我们现在表明，[3,4-³H]DFMA在体内被烟草组织代谢为DL-α-二氟甲基[3,4-³H]鸟氨酸[（3,4-³H]DFMO），这是ODC的类似基于机制的抑制剂。烟草和哺乳动物（小鼠、牛）的精氨酸酶（EC 3.5.3.1）在体外都能将DFMA水解为DFMO，这表明该酶在介导DFMA对烟草中ODC的间接抑制中起作用。这些结果表明，在含有高活性精氨酸酶的组织中，DFMA除了抑制ADC外可能还有其他作用。基于胍丁胺的高效ADC抑制剂的最新进展应该能够在这样的组织中选择性抑制ADC，而不是ODC，因为胍丁胺不是精氨酸酶的底物。
