PYRUVATE CYCLES IN THE METABOLISM OF GLUCOGENIC CELLS

涉及丙酮酸的循环反应已经建立在重要的 脂肪生成和脂肪生成的生物合成途径。 丙酮酸循环 也可能有助于甲状腺功能亢进状态下的产热， 在氨基酸催化剂的调节中起作用。 我们将继续 绘制大鼠肝细胞中各种丙酮酸循环的通量 在不同的饮食方案下，包括禁食、自由进食和 禁食高碳水化合物 我们还将使用来自 链脲佐菌素糖尿病大鼠和甲状腺功能亢进大鼠。 的位点 激素控制的步骤，在周期将探讨使用 抑制剂滴定技术，使用放射性同位素的通量分析， 中间体分析，并使用一些新开发的底物， 不渗透中间体的单酯。 胰高血糖素、肾上腺素的作用 和其它肾上腺素能激动剂、胰岛素和加压素。 我们已经发现，葡萄糖控制乳酸盐的代谢， 在体外生理条件下。 扭转这一局面的因素 葡萄糖的抑制作用将得到更充分的表征;这些 因素包括脂肪酸和乳酸水平，胰高血糖素，但显然 不是肾上腺素 在糖尿病中，这些因素可能会超越正常的葡萄糖 控制生育。 丙酮酸循环中的限速步骤 在植物异生中包括丙酮酸转运，丙酮酸羧化酶， 磷酸烯醇丙酮酸羧激酶和丙酮酸激酶。 代谢 酸中毒时，碳酸氢盐的供应可能是丙酮酸盐 羧化酶和氨甲酰磷酸合成酶， 胚胎发育和尿素生成。 这种影响在 年龄很小可能是婴儿猝死的原因之一。

Cyclic reactions involving pyruvate have been established in the important biosynthetic pathways of gluconeogenesis and lipogenesis. Pyruvate cycles may also contribute to thermogenesis in the hyperthyroid state, and could play a role in the regulation of amino acid catabolism. We will continue to map the fluxes in the various pyruvate cycles in hepatocytes from rats under different dietary regimes, including fasted, ad libitum fed, and fasted-refed high carbohydrate. We will also use hepatocytes from streptozotocin diabetic rats, and from hyperthyroid rats. The sites of hormonal control of the steps in the cycles will be explored using inhibitor titration techniques, flux analysis using radiosotopes, intermediate analysis, and with the use of some newly developed substrates, monoesters of impermeable intermediates. Effects of glucagon, epinephrine and other adrenergic agonists, insulin, and vasopressin will be studied. We have found that glucose control of gluconeogenesis from lactate occurs in vitro under physiological conditions. The factors which reverse this inhibitory effect of glucose will be more fully characterized; these factors include fatty acid and lactate levels, and glucagon, but apparently not epinephrine. In adiabetes, these factors may override normal glucose control of gluconeogenesis. The rate-limiting steps in pyruvate cycling and in gluconeogenesis include pyruvate transport, pyruvate carboxylase, phosphoenolpyruvate carboxykinase and pyruvate kinase. In metabolic acidosis, provision of bicarbonate may be rate-limiting for both pyruvate carboxylase and carbamyl phosphate synthetase, restricting both gluconeogenesis and ureogenesis. Hypoglycemia from such effects in the very young could contribute to the causes of sudden infant death.