A reexamination of the role of the cytosolic alanine aminotransferase in hepatic gluconeogenesis.
A reexamination of the role of the cytosolic alanine aminotransferase in hepatic gluconeogenesis.
复制标题
重新审视胞质丙氨酸转氨酶在肝糖异生中的作用。
DOI：
10.1016/0003-9861(85)90079-7
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发表时间：
1985
影响因子：
3.9
通讯作者：
Olson,MS
中科院分区：
文献类型：
--
作者：
Patel,TB;Olson,MS
在离体灌注大鼠肝脏中，研究了线粒体和细胞质丙氨酸转氨酶同工酶为线粒体室进一步代谢提供丙氨酸丙酮酸的相对重要性。所采用的实验原理基于这样一种假设：丙酮酸转运抑制剂（例如α-氰酸酯）会减少丙氨酸的糖异生和输注[1-14C]丙氨酸的脱羧作用，这与胞质丙氨酸转氨酶对丙酮酸生成的贡献成比例。α-氰肉桂酸抑制24小时禁食大鼠灌注肝脏内源性葡萄糖生成速率。α-氰酸酯对低（1mm）和高（10mm）灌注丙氨酸浓度下[1- 14c]丙氨酸脱羧的抑制率分别为9.5%和42%。在禁食动物的肝脏中灌注1或10丙氨酸，α-氰酸酯引起乳酸和丙酮酸生成速率的显著增加。在肝内灌注丙氨酸时，提高肝生酮率，刺激丙氨酸脱羧和葡萄糖生成的速率；这两个代谢参数的刺激程度被确定为灌注液中丙氨酸浓度的函数。在醋酸盐诱导的生酮过程中，丙氨酸脱羧速率的刺激被α-氰酸酯的注入逆转，同时乳酸和丙酮酸的生成速率也随之增加。结果表明，在快速生酮过程中，丙氨酸的胞内转氨化至少贡献了19%（1丙氨酸）和55%（10丙氨酸）的丙酮酸糖异生。
The relative importance of the mitochondrial and cytosolic alanine aminotransferase isozymes for providing pyruvate from alanine for further metabolism in the mitochondrial compartment was examined in the isolated perfused rat liver. The experimental rationale employed depends upon the supposition that gluconeogenesis from alanine and the decarboxylation of infused [1-14C]alanine should be diminished by pyruvate transport inhibitors (e.g., α-cyanocinnamate) in proportion to the contribution of the cytosolic alanine aminotransferase for generating pyruvate. α-Cyanocinnamate inhibited the endogenous rate of glucose production in perfused livers derived from 24-h-fasted rats. The rate of [1-14C]alanine decarboxylation at low (1 mm) and high (10 mm) perfusate alanine concentrations was inhibited by 9.5 and 42%, respectively, in the presence of α-cyanocinnamate. In livers from fasted animals perfused with either 1 or 10 mmalanine, α-cyanocinnamate caused a substantial increase in the rates of both lactate and pyruvate production. Elevating the hepatic ketogenic rate during infusion of acetate in livers, perfused with alanine, stimulated both the rates of alanine decarboxylation and glucose production; the extent of stimulation of these two metabolic parameters was determined to be a function of the alanine concentration in the perfusate. The stimulation of the rate of alanine decarboxylation during acetate-induced ketogenesis was reversed by coinfusion of α-cyanocinnamate with simultaneous increases in the rates of lactate and pyruvate production. The results indicate that during rapid ketogenesis, cytosolic transamination of alanine contributes at least 19% (at 1 mmalanine) and 55% (at 10 mmalanine) of the pyruvate for gluconeogenesis.