Interface between membrane biology and clinical medicine.
Many enzymes that are embedded within membranes of cells are sensitive to the chemical and physical properties of the lipid components of the membrane. Because of this, the functions of these integral membrane-bound enzymes can be regulated to some extent by changes within the lipid portions of biologic membranes. That the functions of membrane-bound proteins can be manipulated by modifications of their intimate environment is not surprising. It is well known, for example, that the properties of the surrounding aqueous phase can modulate the function of proteins that are soluble in the cytosol of cells. In contrast, whereas significant changes in the chemical composition and physical properties of the aqueous portion of the cell (e.g., ionic strength and pH) are not allowed, normally tolerable fluctuations of diet appear to influence significantly the composition and properties of the lipid portions of intracellular membranes to the extent of altering the function of some membrane-bound enzymes. In addition, it appears that changes of this type can be induced by diseases that alter dietary intake and/or intermediary metabolism. In other words, it is likely that the functions of at least some integral membrane proteins can be manipulated in patients. Such manipulations may prove to be efficacious. Alternatively, the importance of diet and processes of intermediary metabolism for altering the course of certain diseases may not be fully appreciated. It is worthwhile to review, therefore, current ideas of how the lipid portion of a membrane interacts with integral proteins. The property of the lipids that appears to be most important in this regard is their viscosity. The types of manipulations of function of membrane-bound enzymes that can be achieved are illustrated by in vitro effects secondary to varying the lipids used to reconstitute pure, delipidated forms of these enzymes. The functions of pure delipidated enzymes are discussed for the hepatic drug-metabolizing enzyme uridine diphosphoglucuronyltransferase. In addition, data are presented to indicate that the function of this enzyme can be modified extensively in intact animals by changing the diet.
D002462:Cell Membrane / Q000201:enzymology / Q000502:physiology*; D002468:Cell Physiological Phenomena; D002477:Cells / Q000201:enzymology; D055598:Chemical Phenomena; D002621:Chemistry; D004032:Diet; D010743:Phospholipids / Q000378:metabolism / Q000502:physiology; D014539:Uridine Diphosphate Sugars / Q000378:metabolism / Q000502:physiology
D010743:Phospholipids; D014539:Uridine Diphosphate Sugars