Landau B R, Schumann W C, Chandramouli V, Magnusson I, Kumaran K, Wahren J
Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106.
Am J Physiol. 1993 Oct;265(4 Pt 1):E636-47. doi: 10.1152/ajpendo.1993.265.4.E636.
Purposes of this study were 1) to estimate in humans, using 14C-labeled propionate, the rate of hepatic gluconeogenesis relative to the rate of Krebs cycle flux; 2) to compare those rates with estimates previously made using [3-14C]lactate and [2-14C]acetate; 3) to determine if the amount of ATP required for that rate of gluconeogenesis could be generated in liver, calculated from that rate of Krebs cycle flux and splanchnic balance measurements, previously made, and 4) to test whether hepatic succinyl-CoA is channeled during its metabolism through the Krebs cycle. [2-14C]propionate, [3-14C]-propionate, and [2,3-14C]succinate were given along with phenyl acetate to normal subjects, fasted 60 h. Distributions of 14C were determined in the carbons of blood glucose and of glutamate from excreted phenylacetylglutamine. Corrections to the distributions for 14CO2 fixation were made from the specific activities of urinary urea and the specific activities in glucose, glutamate, and urea previously found on administering [14C]-bicarbonate. Uncertainties in the corrections and in the contributions of pyruvate and Cori cyclings limit the quantitations. The rate of gluconeogenesis appears to be two or more times the rate of Krebs cycle flux and pyruvate's decarboxylation to acetyl-CoA, metabolized in the cycle, less than one-twenty-fifth the rate of its decarboxylation. Such estimates were previously made using [3-14C]lactate. The findings support the use of phenyl acetate to sample hepatic alpha-ketoglutarate. Ratios of specific activities of glucose to glutamate and glucose to urinary urea and expired CO2 indicate succinate's extensive metabolism when presented in trace amounts to liver. Utilizations of the labeled compounds by liver relative to other tissues were in the order succinate = lactate > propionate > acetate. ATP required for gluconeogenesis and urea formation was approximately 40% of the amount of ATP generated in liver. There was no channeling of succinyl-CoA in the Krebs cycle in the hepatic mitochondria.
1）在人体中，使用14C标记的丙酸盐，估计肝脏糖异生速率相对于三羧酸循环通量的速率；2）将这些速率与先前使用[3-14C]乳酸盐和[2-14C]乙酸盐所做的估计值进行比较；3）根据先前进行的三羧酸循环通量速率和内脏平衡测量结果，确定肝脏中能否产生该糖异生速率所需的ATP量；4）测试肝脏琥珀酰辅酶A在其代谢过程中是否通过三羧酸循环进行通道化运输。将[2-14C]丙酸盐、[3-14C]丙酸盐和[2,3-14C]琥珀酸盐与苯乙酸一起给予禁食60小时的正常受试者。通过排泄的苯乙酰谷氨酰胺测定血糖和谷氨酸碳中14C的分布。根据尿尿素的比活以及先前给予[14C]碳酸氢盐时在葡萄糖、谷氨酸和尿素中发现的比活，对14CO2固定的分布进行校正。校正过程以及丙酮酸和科里循环贡献的不确定性限制了定量分析。糖异生速率似乎是三羧酸循环通量速率的两倍或更多倍，丙酮酸脱羧生成乙酰辅酶A并在循环中代谢的速率，不到其脱羧速率的二十五分之一。先前使用[3-14C]乳酸盐也得出了这样的估计值。这些发现支持使用苯乙酸对肝脏α-酮戊二酸进行取样。葡萄糖与谷氨酸、葡萄糖与尿尿素以及呼出CO2的比活比值表明，当微量给予肝脏时，琥珀酸盐会进行广泛的代谢。肝脏相对于其他组织对标记化合物的利用率顺序为：琥珀酸盐 = 乳酸盐 > 丙酸盐 > 乙酸盐。糖异生和尿素形成所需的ATP约为肝脏中产生的ATP量的40%。肝脏线粒体的三羧酸循环中不存在琥珀酰辅酶A的通道化运输。
