PROPIONATE UTILIZATION, GLUCONEOGENESIS, & PYRUVATE RECYCLING IN HUMAN LIVER

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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)