Bennet, W. M.

Animal studies have shown that pancreatic enzyme secretion is independent of enzyme synthesis. To investigate this relationship in humans, we have coinfused 14C-labeled leucine tracer with cholecystokinin octapeptide in nine healthy adults for 4 h and measured the rate of appearance of secreted and newly labeled enzymes in the duodenum. Enzyme secretion was well maintained throughout, but newly labeled enzymes only appeared in juice between 75 and 101 min (median time, 86 min), indicating that initial secretion was dependent on the release of zymogen stores and that the median production time for new enzymes was 86 min. Between 85 and 225 min there was a curvilinear increase in the enrichment of secreted enzymes with newly synthesized enzymes, suggesting a median turnover rate of zymogen stores of 29%/h (range 12-47%/h). In conclusion, our results suggest that in healthy humans, postprandial pancreatic enzyme secretion is maintained by the export of a large stored pool and is not rate limited by enzyme synthesis, since it takes approximately 86 min for newly synthesized enzymes to take part in the digestive process.

To assess the contributions of leucine and alpha-ketoisocaproate (KIC) derived from the portal vein vs. hepatic artery for hepatic protein synthesis, 14-postabsorptive dogs were infused simultaneously with [1-14C]- and [4,5-3H]leucine or [1-14C]- and [4,5-3H]KIC. On one occasion one tracer was infused via a leg vein and the other via mesenteric infusion catheters, and dogs were restudied with both tracers infused systemically. The ratios of systemically to portally infused tracers in portal and arterial plasma leucine were used as indexes of the radioactivity in the potential precursor pools and in fibrinogen-bound leucine as a paradigm of hepatic protein synthesis. In the dogs given leucine tracers, the relative proportions of systemically to portally infused radioactivity in portal free leucine (0.50 +/- 0.06) were lower (P less than 0.001) than in arterial free leucine (1.22 +/- 0.03) and not different from that bound in fibrinogen (0.43 +/- 0.02). In the dogs infused intraportally with KIC, these values were 0.81 +/- 0.04, 0.97 +/- 0.05, and 0.74 +/- 0.05, respectively. In the control studies these ratios were not significantly different from the expected value of 1.0. The results suggest that, in postabsorptive dogs, fibrinogen is exclusively synthesized from portally delivered leucine with little or no contribution from the hepatic artery, whereas portally delivered KIC contributes little directly to fibrinogen synthesis. These data are consistent with zonation of hepatic amino acid metabolism and/or protein synthesis.