Lau C, Slotkin T A
Eur J Pharmacol. 1982 Feb 19;78(1):99-105. doi: 10.1016/0014-2999(82)90376-4.
The activity of rat heart ornithine decarboxylase (ODC), the enzyme involved in the initial step of polyamine biosynthesis, was markedly stimulated after isoproterenol treatment, reaching a maximum of about four times the basal value four hours after administration. At all times after isoproterenol, kinetic studies revealed only two forms of the enzyme with Km values for ornithine of 35-50 microM and 190 microM, compared to only one form (190 microM) in the controls. At no time was a form of ODC with an intermediate Kornm detected, nor did dialysis reverse stimulation of activity of enzyme from isoproterenol-treated rats, or increase activity in control preparations; it is therefore unlikely that small molecular activators or inhibitors participate in the stimulation. The time course of Vmax values for the high-affinity component of the enzyme coincided with that of net enzyme activity, indicating that increases of ODC activity in response to isoproterenol might result from a shift of enzyme from its low-affinity state to the high-affinity form, rather than from appearance of additional enzyme molecules. In support of this hypothesis, alpha-difluoromethylornithine, an irreversible ODC inhibitor, displayed identical ID50 values in control and isoproterenol-treated animals, a situation which would not occur if more enzyme were present. These data are consistent with the view that post-translational control mechanisms involving macromolecular factors could operate in regulating cardiac ODC activity.
大鼠心脏鸟氨酸脱羧酶（ODC）是参与多胺生物合成第一步的酶，异丙肾上腺素处理后其活性受到显著刺激，给药后4小时达到最大值，约为基础值的四倍。在异丙肾上腺素处理后的所有时间点，动力学研究仅揭示出该酶的两种形式，其对鸟氨酸的Km值分别为35 - 50微摩尔和190微摩尔，而对照组中只有一种形式（190微摩尔）。未检测到具有中间Km值的ODC形式，透析也不能逆转异丙肾上腺素处理大鼠的酶活性刺激，或增加对照制剂中的活性；因此，小分子激活剂或抑制剂不太可能参与这种刺激。该酶高亲和力组分的Vmax值随时间变化的过程与净酶活性的变化过程一致，这表明异丙肾上腺素引起的ODC活性增加可能是由于酶从低亲和力状态转变为高亲和力形式，而不是由于额外酶分子出现。支持这一假设的是，不可逆的ODC抑制剂α-二氟甲基鸟氨酸在对照动物和异丙肾上腺素处理的动物中显示出相同的ID50值，如果存在更多的酶，这种情况不会发生。这些数据与以下观点一致，即涉及大分子因子的翻译后控制机制可能在调节心脏ODC活性中起作用。
