A 30 cm segment of the duodenum, jejunum, or ileum of normal human volunteers was perfused, on separate occasions, with test solutions containing either glycylglycine, free glycine, glycylleucine, or equimolar amounts of free glycine and free leucine. Luminal fluid contained no hydrolytic activity against glycylglycine and minimal activity against glycylleucine. In each intestinal segment, amino acid absorption rates were significantly greater from the test solutions containing the same amount of amino acids in dipeptide than in free form (as high as 185% increase). Perfusion of each intestinal segment with a test solution containing the equimolar mixture of free glycine and free leucine always resulted in a greater leucine than glycine absorption rate. This preferential absorption of leucine, however, was either diminished (jejunum) or almost abolished (duodenum and ileum) when the glycylleucine solution instead of the equimolar mixture was presented to the intestinal mucosa. Among the three segments, the duodenum exhibited the least potential for the disappearance of dipeptides. The jejunal and ileal dipeptide disappearance rates were either similar for glycylleucine (94% vs. 92%) or slightly different for glycylglycine (92% vs. 79%). Despite lack of a remarkable difference in the disappearance rates, absorption rates of constituent amino acids were markedly greater in the jejunum than in the ileum. This reduced amino acid absorption was brought about by a greater accumulation of free amino acids in the lumen of the ileal segment in the lumen than when the glycylglycine test solution did not contain free leucine. Similarly, inhibition of free glycine and free leucine absorption by isoleucine was not accompanied by any remarkable alteration of absorption rates of the constituent amino acids of glycylleucine. The results of these studies suggest that: (a) dipeptide disappearance in the gut lumen is principally accomplished by intact absorption and not by hydrolysis; (b) intracellular hydrolysis of dipeptides is markedly greater in the ileum than in the jejunum, while dipeptide absorption rates are either similar or only slightly different in these two segments; (c) there is no appreciable hydrolysis of glycylglycine by the membrane-bound enzymes and only a small fraction of glycylleucine is hydrolyzed by these enzymes.
A B S T R A C T The intestinal fate of two tripeptides (triglycine and trileucine). which differ markedly in solubility and molecular weight, have been investigated by jejunal perfusion in healthy human volunteers. Rates of glycine or leucine uptake from test solutions containing triglycine or trileucine were greater than from test solutions containing corresponding amounts of free glycine or free leucine, respectively. The rate of glycine uptake from a 100 mM triglycine solution was greater than that from a 150 mM diglycine solution. At each infused load of triglycine (e.g., 1,000 imol/min) the rates (micromoles/minute per 30 cm) of either triglycine disappearance (810±40) or glycine absorption (2,208±+122) were markedly greater than the luminal accumulation rates of either diglycine (56±10) or free glycine (110±18). The luminal accumulation rate of free leucine during infusion of a 5 mM trileucine solution was over threefold greater than that of free glycine during the infusion of a 5 mM triglycine solution. Luminal fluid exhibited no hydrolytic activity against triglycine, but contained some activity against trileucine. Saturation of free amino acid carrier system with a large load of leucine did not affect glycine absorption rate from a triglycine test solution, but isoleucine markedly inhibited the uptake of leucine from a trileucine solution. When the carrier system for dipeptides was saturated with a large amount of glycyl-A preliminary account of this work has been previously published (1974. Gastroenterology. 66: 657) leucine, the disappearance rate of triglycine was considerably reduced while that of trileucine remained unaffected. After addition of glycylleucine to tripeptide solutions, there was a minimal increase in the luminal accumulation of diglycine, while dileucine accumulation was increased by 62-fold.These studies suggest that the modes of intestinal disappearance of the above two tripeptides are different. Triglycine is taken up intact by human jejunum; this uptake is mediated totally or partially by the carrier system which also transports dipeptides. In contrast, trileucine is hydrolyzed to leucine and dileucine mostly on the cell surface and a small fraction is hydrolyzed in the gut lumen; these hydrolytic products are then taken up by the free amino acid and dipeptide carrier systems, respectively.
Many researchers believe that groupware can only be evaluated by studying real collaborators in their real contexts, a process that tends to be expensive and timeconsuming. Others believe that it is more practical to evaluate groupware through usability inspection methods. Deciding between these two approaches is difficult, because it is unclear how they compare in a real evaluation situation. To address this problem, we carried out a dual evaluation of a groupware system, with one evaluation applying user-based techniques, and the other using inspection methods. We compared the results from the two evaluations and concluded that, while the two methods have their own strengths, weaknesses, and trade-offs, they are complementary. Because the two methods found overlapping problems, we expect that they can be used in tandem to good effect, e.g., applying the discount method prior to a field study, with the expectation that the system deployed in the more expensive field study has a better chance of doing well because some pertinent usability problems will have already been addressed.
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