PROPIONATE UTILIZATION, GLUCONEOGENESIS, & PYRUVATE RECYCLING IN HUMAN LIVER

我们最近进行了试验研究与禁食的人 志愿者口服[U-13 C]丙酸盐。 在摄入 ~1.5 g [U-13 C]丙酸盐时， 2 - 3小时内多种富集的血浆葡萄糖种类， 证明[U-13 C]丙酸盐的快速和广泛掺入 单位进入异生。 葡萄糖酸盐的碳1、2、5和6 显示出相同的富集动力学，达到峰值富集 约4.5%，而碳3和4达到约4.5%的峰值富集。 百分之二点五 在120至180分钟之间，所有六种葡萄糖的富集 碳保持相对恒定。 然而，尿葡糖苷酸 标签，这是监测长达6小时后摄入显示， 在3 - 4小时内，己糖富集设置下降，表明 [U-13 C]丙酸盐的消耗。 没有[U-13C]丙酸盐 在任何血浆样品中检测到，表明其完全 从摄入后0 - 3小时从循环中清除。 为 随后的时间点，葡萄糖的C2共振的同位素异构体分析 提供了回补、丙酮酸再循环的相对通量值， 分别为5.92、3.55和2.37（相对湿度 至柠檬酸合酶通量为1.0）。 这些相对通量估计值为 与其他人使用[3 - 14C]乳酸盐报告的结果一致， 表明肝脏丙酮酸循环活性高。 （协作 9)报告期：（一九九七年九月一日至一九九八年八月三十一日）

We have recently performed trial studies with fasted human volunteers given [U-13C]propionate orally. Following ingestion of ~1.5 g [U-13C]propionate, there was a rapid evolution of multiply-enriched plasma glucose species within 2-3 hours, demonstrating rapid and extensive incorporation of [U-13C]propionate units into gluconeogenesis. Carbons 1, 2, 5, and 6 of gluconate showed identical enrichment kinetics, reaching a peak enrichment of about 4.5%, while carbons 3 and 4 reached peak enrichments of about 2.5%. Between 120 and 180 minutes, enrichment of all six glucose carbons remained relatively constant. However, urinary glucuronide labeling, which was monitored up to 6 hours post-ingestion showed a decline in the hexose enrichment setting in at 3-4 hours, indicating depletion of the [U-13C]propionate. No [U-13C]propionate was ever detected in any of the blood plasma samples, indicating its complete removal from the circulation from 0-3 hours post ingestion. For the later time-points, isotopomer analysis of the C2 resonance of glucose provided relative flux values for anaplerosis, pyruvate recycling, and gluconeogenic fluxes of 5.92, 3.55, and 2.37, respectively (relative to a citrate synthase flux of 1.0). These relative flux estimates are consistent with those reported by others using [3-14C]lactate and indicate a high activity of hepatic pyruvate cycling. (Collaborative 9) REPORT PERIOD: (09/01/97-08/31/98)