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New Insights into Gastrointestinal and Liver Diseases Based on Molecular Aspects of Transport Physiology
  1. Kim E. Barrett,
  2. Richard H. Moseley
  1. 1From the Department of Medicine, University of California, San Diego, School of Medicine, San Diego, Calif. (K.E.B.)
  2. 2Department of Medicine, Ann Arbor VA Medical Center, and University of Michigan School of Medicine, Ann Arbor, Mich. (R.H.M.).
  1. Address correspondence to: Kim E. Barrett, PhD, University of California at San Diego Medical Center, 8414, 200 W. Arbor Drive, San Diego, CA 92103-8414. E-mail: kbarrett{at}ucsd.edu

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The transport of electrolytes and other solutes across the hydrophobic barrier of cell membranes is an energetic problem that has occupied several generations of physiologists and other scientists. The relative impermeability of cell membranes to the majority of solutes important for cellular homeostasis, and the function of specialized biochemical pathways mandates that selective mechanisms have evolved to increase the rate of passage of such solutes into the cell. Indeed, it has been estimated that at least 5% of the proteins encoded by most genomes subserve membrane transport functions. This implies that some thousands of human proteins are transporters, many of which we have little or no knowledge of as yet. However, our understanding of the molecular physiology of such membrane transport proteins is expanding exponentially, in part because of the development of sophisticated methodologies that allow us to probe the function of these molecules in ever greater detail. Perhaps not surprisingly, such studies are also revealing that some individuals harbor genetic defects in the structure of membrane transport molecules, which can result in altered function and/or membrane trafficking and thus lead to a compromise in cellular functions.

In some tissues, the challenges inherent in membrane transport are magnified, in that solutes must traverse not just one membrane barrier but two. This is the case for tissues lined with polarized, transporting epithelia, where the asymmetrical arrangement of transporters provides for the net movement of electrolytes or other solutes across an epithelial barrier, either from the bloodstream …

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