Physiological Transport Systems

Physiological Buffer Systems Recently, a lot of efforts have been made on how to increase the biorelevance of the Caco-2 model [63, 47, 64, 65,105], Historically, the media used for Caco-2 experiments were buffered at pH 7.4 on both sides of the monolayer. The pH in the cellular interstice and blood compartment is known to be 7.4. However, the pH in the upper GI tract under fasted conditions ranges from 5.0 to 6.5, with an acidic microclimate existing just above the epithelial cell layer estimated to be between 5.8 and 6.3 [90], The pH of the apical medium can have a critical effect on the transport of drugs, especially for drugs with a pKa close to 7, or when pH-dependent transporters are involved. 

Bi2 are only about 2 meg, it would take about 5 years for all of the stored vitamin B12 to be exhausted and for megaloblastic anemia to develop if Bi2 absorption were stopped. Vitamin B12 in physiologic amounts is absorbed only after it complexes with intrinsic factor, a glycoprotein secreted by the parietal cells of the gastric mucosa. Intrinsic factor combines with the vitamin Bi2 that is liberated from dietary sources in the stomach and duodenum, and the intrinsic factor-vitamin Bi2 complex is subsequently absorbed in the distal ileum by a highly selective receptor-mediated transport system. Vitamin Bi2 deficiency in humans most often results from malabsorption of vitamin B12 due either to lack of intrinsic factor or to loss or malfunction of the specific absorptive mechanism in the distal ileum. Nutritional deficiency is rare but may be seen in strict vegetarians after many years without meat, eggs, or dairy products. 

Biological Implications of Structural and Electrical Properties of Lipids. It is rather obvious that the structure of lipids is very important in connection with the function of living cells since most physiological processes occur in lipid environment. There is, for example, evidence that lipid-protein complexes are necessary for the proper functioning of mitochondria (56). Although lipids are most important in providing a suitable material for functional complexes (ionic channels, electron transport systems, receptor units, etc.), their own physical properties are certainly... 

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