Diffusion carrier-mediated

Substances can be transported across epithelial membranes by simple passive diffusion, carrier-mediated diffusion, and active transport, in addition to other specialized mechanisms, including endocytosis. 

J.S. Schultz, J.D. Goddard and S.R. Suchdeo, Facilitated Transport via Carrier-mediated Diffusion in Membranes, AIChE 7. 20, 417 (1974). 

Most tissues contain very little free riboflavin and, except in the kidneys, where 30% is as riboflavin phosphate, more than 80% is FAD, almost all bound to enzymes. Isolated hepatocytes (and presumably other tissues) show saturable concentrative uptake of riboflavin. The of the uptake process is the same as that of flavokinase, and uptake is inhibited by inhibitors of flavokinase, suggesting that tissue uptake is the result of carrier-mediated diffusion, fol-lowedbymetabolic trapping as riboflavin phosphate, then onward metabolism to FAD, catalyzed by FAD pyrophosphorylase. FAD is a potent inhibitor of the pyrophosphorylase and acts to limit its own synthesis. FAD, which is not protein bound is rapidly hydrolyzed to riboflavin phosphate by nucleotide pyrophosphatase unbound riboflavin phosphate is similarly rapidly hydrolyzed to riboflavin by nonspecific phosphatases (Aw et al., 1983 Yamada et al., 1990). 

The phosphorylated vitamers are dephosphorylated by membrane-bound alkaline phosphatase in the intestinal mucosa pyridoxal, pyridoxamine, and pyridoxine are all absorbed rapidly by carrier-mediated diffusion. Intestinal mucosal cells have pyridoxine kinase and pyridoxine phosphate oxidase (see Figure 9.1), so that there is net accumulation of pyridoxal phosphate by metabolic trapping. Much of the ingested pyridoxine is released into the portal circulation as pyridoxal, after dephosphorylation at the serosal surface. 

Tissue uptake of vitamin Be is again by carrier-mediated diffusion of pyridoxal (and other unphosphorylated vitamers), followed by metabolic trapping by phosphorylation. Circulating pyridoxal and pyridoxamine phosphates are hydrolyzed by extracellular alkaline phosphatase. All tissues have pyridoxine kinase activity, but pyridoxine phosphate oxidase is found mainly in the liver, kidney, and brain. 

The characteristic of a facilitated or carrier-mediated transport is the occurrence of a reversible chemical reaction or complexation process in combination with a diffusion process. This implies that either the diffusion or the reaction is rate limiting The total flux of a permeant A will thus be the sum of both the Fickian diffusion and the carrier-mediated diffusion as illustrated in Equation 4.19 [46] ... 

Even if glucose were converted into pyruvate by glycolysis, the pyruvate would be reduced by cytosolic NADH into lactate. Lactate leaves the cytoplasm by carrier-mediated diffusion and enters the bloodstream, from which it is taken up by the liver and heart muscle. 

Schultz, J.S., Goddard, J.D. and S.R. Suchdeo. "Facilitated transport via carrier-mediated diffusion in membranes. Part I Mechanistic aspects, experimental systems and characteristic regimes." American Institute of Chemical Engineers Journal 20 (1974) 417-445. 

Gambale, F., Gliozzi, A., Robello, R., 1973. Determination of rate constants in carrier-mediated diffusion through lipid bilayers. Biochim. Biophys. Acta 330 325. 

Compounds that are lipid soluble will diffuse freely across cell membranes, as they can dissolve in the lipid of the membrane - this is passive diffusion. Hydrophilic compounds require a transport protein in order to cross the lipid membrane - this is facilitated or carrier-mediated diffusion. Neither passive nor facilitated diffusion alone can lead to the concentration of the transported material being greater inside the cell than outside. 

In the case of a hydrophilic compound that enters the cell by carrier-mediated diffusion, a net increase in concentration inside the cell can sometimes be achieved by binding it to an intracellular protein. Only material in free solution can equilibrate across the membrane, not that which is protein bound. Such binding proteins are important, for example, in the intestinal absorption of calcium (section 4.6.1) and iron (section 4.6.2). 

Glucose enters cells by carrier-mediated diffusion. Once inside the cell, it is phosphorylated to glucose 6-phosphate, a reaction catalysed by the enzyme hexokinase, using ATP as the phosphate donor (section 5.4.1 and Problem 2.1). Glucose 6-phosphate does not cross cell membranes, and therefore there is a net accumulation of [glucose plus glucose 6-phosphate] inside the cell, at the expense of 1 mol of ATP utilized per mole of glucose trapped in this way. Vitamins (riboflavin section 11.7.1) and Bg (section 11.9.1) are similarly accumulated inside cells by phosphorylation at the expense of ATE... 

Minerals generally enter the intestinal mucosal cells by carrier-mediated diffusion and are accumulated intracellularly by binding to specific binding proteins (section... 

Other monosaccharides are absorbed by carrier-mediated diffusion there are at least three distinct carrier proteins one for fructose, one for other monosaccharides and one for sugar alcohols. Because they are not actively transported, fructose and sugar alcohols are absorbed only to a limited extent, and after a moderately high intake a significant amount will avoid absorption and remain in the intestinal lumen, acting as a substrate for colon bacteria and, like unabsorbed disaccharides in people with disaccharidase deficiency, causing abdominal pain and diarrhoea. 

Most minerals are absorbed by carrier-mediated diffusion into intestinal mucosal cells and accumulated by binding to intracellular proteins. There is then sodium-dependent active transport from the epithelial cells into the bloodstream, where again they are usually bound to transport proteins. Genetic defects of the intracellular binding proteins or the active transport systems at the basal membrane of the mucosal cell can result in functional deficiency despite an apparently adequate intake of the mineral. 

In the liver, glucose uptake is by carrier-mediated diffusion and metabolic trapping as glucose 6-phosphate (section 3.2.2.2), and is independent of insulin. The uptake of glucose into the liver increases very significantly as the concentration of glucose in the portal vein increases, and the liver has a major role in controlling the amount of... 

Both pyridoxal and the phosphate circulate in the bloodstream the phosphate is dephosphorylated by extracellular alkaline phosphatase, and tissues take up pyridoxal by carrier-mediated diffusion, followed by metabolic trapping as phosphate esters. Pyridoxine and pyridoxamine phosphates are oxidized to pyridoxal phosphate (Figure 1). 

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