The structure and biochemistry of the vacuolar H+ ATPase in proximal and distal urinary acidification |
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Authors: | Stephen L Gluck MD |
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Institution: | (1) Departments of Medicine and Cell Biology and Physiology, Washington University School of Medicine, USA;(2) the Renal Division, Department of Medicine, Jewish Hospital of St. Louis, St. Louis, Missouri |
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Abstract: | Vacuolar H+ ATPases participate in renal hydrogen ion secretion in both the proximal and distal nephron. These plasma membrane forms of the vacuolar H+ ATPase are regulated physiologically to maintain the acid-base balance of the organism. Proton transporting renal cells have requirements for constitutive acidification of intracellular compartments for normal endocytic and secretory functions. Recent experiments have begun to reveal how the kidney regulates these proton pumps independently. Vacuolar H+ ATPases are a family of structurally similar enzyme which differ in the composition of specific subunits. Cytosolic regulatory enzymes are present in renal cells which may affect vacuolar H+ ATPases in certain membrane compartments selectively. The vacuolar H+ ATPase in the plasma membrane of intercalated cells resides in a specialized proton-transporting apparatus that translocates the enzyme between an intracellular membrane pool and the plasma membrane in response to physiologic stimuli.This review will focus on the structure, enzymology, and regulation of the vacuolar H+ ATPase in the mammalian kidney. Because of space limitations, it will cover predominantly work from our laboratory. However, a number of investigators, including Brown (Brownet al., 1987, 1988a,b, 1989), Burckhardt (Sabolicet al., 1985; Turriniet al., 1989; Simon and Burckhardt, 1990), Madsen and Tisher (Madsen and Tisher, 1985; Verlanderet al., 1987, 1989). Steinmetz (Steinmetz, 1986; Stetson and Steinmetz, 1986), Schwartz (Scwartzet al., 1985, 1988; Satlin and Schwartz, 1989), Sabatini and Kurtzman (Sabatiniet al., 1990a,b), DuBose (Diaz-Diazet al., 1986; Gurich and DuBose, 1989), Al-Awqati (Van Adelsberg and Al-Awqati, 1986), and their coworkers, and many other investigators have made important contributions to this field. |
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Keywords: | Kidney collecting tubule intercalated cells urinary acidification acid-base balance proton pump V-ATPase regulatory proteins |
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