Derek F. Evered

Absorption of glutathione from the gastro-intestinal tract

Transport of the peptide glutathione (GSH) has been studied with the rat small intestine in vitro and the human buccal cavity in vivo. Uptake was found to be sodium-independent in both systems. Saturation kinetics were demonstrated and uptake did not require energy in either system. Transport was inhibited by other small peptides. Carrier-mediated facilitated diffusion was postulated as the mode of transport.

Characteristics of L-citrulline transport across rat small intestine in vitro

ABSTRACT: The amino acid L-citulline is an important intermediate of urea cycle and a key precursor for arginine biosynthesis. We have examined the characteristics of citrulline transport across the everted sacs of the rat small intestine. Our studies suggest that the optimal site of citrulline absorption is middle to lower ileum. It shows active transport, and this transport is predominantly Na+ dependent. Its uptake is significantly inhibited by ouabain, dinitrophenol, sodium azide, and sodium cyanide. Kinetic estimation reveal an apparent substrate concentration at ½ maximum velocity of 4.10 ± 0.86 mM and a Vmax, of 18.7 ± 1.66 μmol/g wet weight tissue/30 min. Analog inhibition studies suggest that citrulline may share the neutral brush border system described for the mucosal brush border membranes of the rabbit jejunum or a system analogous to system ASC described for nonepithelial cells and for basolateral membranes of certain epithelia. In conclusion, the rat small intestine has developed a specific carrier-mediated, Na+-dependent pathway for citrulline absorption.

Absorption of nicotinic acid and nicotinamide from rat small intestine in vitro

Intestinal absorption of nicotinic acid and nicotinamide was studied using everted sacs of rat small intestine. Transport down the concentration gradient showed saturation kinetics at low concentrations and linear kinetics at higher concentrations. Addition of ouabain or omission of sodium ions decreased absorption. Neither compound was absorbed against a concentration gradient. The mode of transport was thought to be carrier-mediated facilitated diffusion at lower concentrations masked by passive diffusion at higher concentrations.

Transamination pathways influencing l-glutamine and l-glutamate oxidation by rat enterocyte mitochondria and the subcellular localization of l-alanine aminotransferase and l-aspartate aminotransferase

Using analytical subcellular fractionation techniques, 12% of the total L-alanine aminotransferase activity and 26% of the total L-aspartate aminotransferase activity was localized in enterocyte mitochondria. Alanine and aspartate were products from the oxidation of glutamine and glutamate by enterocyte mitochondria. At low concentrations, malate stimulated aspartate synthesis but was inhibitory at higher concentrations. The malate inhibition of aspartate synthesis, which increased in the presence of pyruvate, was accompanied by an increase in alanine synthesis. With glutamine as substrate in the presence of pyruvate and malate, alanine synthesis was increased by 127% on addition of purified L-alanine aminotransferase, in spite of large amounts of glutamate generated. It was concluded that when pyruvate is available the important route for glutamine or glutamate oxidation by transamination was via L-alanine:2-oxoglutarate aminotransferase and not via L-aspartate:2-oxoglutarate aminotransferase. Results suggested that mitochondria may account for 50% of alanine production from glutamine in the enterocyte despite the relatively low activity of L-alanine aminotransferase therein.

Absorption of lactulose from mammalian gastrointestinal tract.

1. The disaccharide lactulose (galactosyl-beta-1,4-fructose) was poorly absorbed from rat small intestine in vitro and human mouth in vivo. 2. These results confirm indirect clinical evidence of poor absorption from the intestine. 3. The presence of calcium ions, or absence of sodium ions, had no effect on lactulose absorption from buccal cavity. 4. The presence of ouabain, or absence of Na+, did not increase the absorption of lactulose from small intestine. 5. It is thought that the mode of transport, in both instances, is by passive diffusion with the concentration gradient.

Absorption of amino acids from the human mouth

SummaryCertain amino acids were transported across buccal mucosa in vivo by a carrier-mediated process. Metabolic loss of L-amino acids from the mouth in a 5 min test period was negligible. The buccal mucosal transport process was stereospecific for most L-amino acids tested. The uptake of L-methionine and L-leucine showed a tendency to saturation with increasing substrate concentration. The absorption of L-leucine, L-isoleucine and L-methionine as single amino acids was inhibited in the presence of each other suggesting at least one common transport mechanism. Administration of equimolar amounts of amino acids revealed a specific pattern of absorption that could be classified into fast, intermediate, and slow groups. Absorption of some amino acids was at least partly dependent on the presence of sodium ions in the luminal solution. In conclusion, our studies demonstrate that the human buccal mucosa is permeable to L-amino acids in a selective manner, and may resemble absorption pattern similar to other locations of the gastrointestinal tract.

Absorption of homocitrulline from the gastrointestinal tract

1. Transport of L-homocitrulline, an amino acid which occurs in milk products, was studied with rat small intestine in vitro and from the human mouth in vivo. Absorption was partially dependent, in both systems, on the presence of sodium ions. 2. Metabolic inhibitors decreased L-homocitrulline uptake across the small intestine. Transport across the intestine did not occur against the concentration gradient but did show saturation kinetics. 3. The barbiturate, amytal, did not inhibit buccal absorption. Saturation kinetics were demonstrated. 4. Experiments were conducted with L-citrulline, or other amino acids, as possible inhibitors of L-homocitrulline transport. Results were compatible with Na+-dependent carrier-mediated uptake across the buccal mucosa. Active transport could be involved with the small intestine assuming that L-homocitrulline has a low affinity for the carrier system.