Morris J E, Peraino C
J Biol Chem. 1976 May 10;251(9):2571-8.
Previous studies of serine dehydratase (EC 4.2.1.13) and ornithine aminotransferase (EC 2.6.1.13) adaptation in rat liver showed that in rats on a high protein diet, glucocorticoid administration increased serine dehydratase activity while simultaneously reducing the activity of ornithine aminotransferase. The present study examines the role of enzyme synthesis in the expression of these and other dissimilar adaptive characteristics of the two enzymes. Both enzymes were purified to crystallinity and used to prepare specific antibodies. Changes in the rate of synthesis of each enzyme during adaptation were then measured immunochemically. In rats fed ad libitum, the synthetic rates for both enzymes exhibited circadian rhythm, although enzyme levels remained relatively constant. The circadian cycle for ornithine aminotransferase synthesis was in phase with the cycles for body weight and relative liver weight (maxima at 9 a.m., minima at 9 p.m.) but was approximately 12 hours out of phase with the cycle for serine dehydratase synthesis. 9alpha-Fluoro-11beta, 21-dihydroxy-16alpha, 17alpha-isopted at 9 a.m., increased serine dehydratase synthesis and simultaneously decreased the synthesis of ornithine aminotransferase. When triamcinolone was injected at 9 p.m., however, serine dehydratase synthesis was not stimulated, although the reduction of ornithine aminotransferase synthesis was still produced. These results suggest that: (a) circadian cycling of synthesis may be a general phenomenon in enzyme regulation even though for enzymes with relatively long half-lives, such cycling may not be reflected as fluctuations in enzyme levels; (b) such circadian rhythmicity may also involve cyclic changes in the responsiveness of the enzyme-forming system to regulatory stimuli; (c) whereas the adaptive behavior of serine dehydratase typifies that of amino acid-catabolizing enzymes in general, the responses of ornithine aminotransferase denote a functional association of this enzyme with anabolic processes. On this basis, the possibility that ornithine aminotransferase plays a pivotal role in the regulation of urea cycle activity and nitrogen balance is discussed.
以往对大鼠肝脏中丝氨酸脱水酶（EC 4.2.1.13）和鸟氨酸氨基转移酶（EC 2.6.1.13）适应性的研究表明，在高蛋白饮食的大鼠中，给予糖皮质激素会增加丝氨酸脱水酶的活性，同时降低鸟氨酸氨基转移酶的活性。本研究探讨了酶合成在这两种酶以及其他不同适应性特征表达中的作用。两种酶均被纯化至结晶状态，并用于制备特异性抗体。然后通过免疫化学方法测定适应过程中每种酶的合成速率变化。在自由采食的大鼠中，尽管酶水平保持相对恒定，但两种酶的合成速率均呈现昼夜节律。鸟氨酸氨基转移酶合成的昼夜周期与体重和相对肝脏重量的周期同步（上午9点达到最大值，晚上9点达到最小值），但与丝氨酸脱水酶合成的周期相差约12小时。上午9点注射9α-氟-11β,21-二羟基-16α,17α-异丙基皮质醇，可增加丝氨酸脱水酶的合成，同时降低鸟氨酸氨基转移酶的合成。然而，当在晚上9点注射曲安西龙时，虽然仍能降低鸟氨酸氨基转移酶的合成，但不会刺激丝氨酸脱水酶的合成。这些结果表明：（a）合成的昼夜循环可能是酶调节中的普遍现象，即使对于半衰期相对较长的酶，这种循环可能不会表现为酶水平的波动；（b）这种昼夜节律性也可能涉及酶形成系统对调节刺激的反应性的周期性变化；（c）虽然丝氨酸脱水酶的适应性行为一般代表氨基酸分解代谢酶的适应性行为，但鸟氨酸氨基转移酶的反应表明该酶与合成代谢过程存在功能关联。在此基础上，讨论了鸟氨酸氨基转移酶在尿素循环活性调节和氮平衡中起关键作用的可能性。
