Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.3.1 (Mg2+-ATPase)
 1,484 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The transbilayer reorientation (flip-flop) of the long-chain amphiphilic anion DENSA (5-(N-decyl)aminonaphthalene-2-sulfonic acid) in the erythrocyte membrane was studied by fluorescence spectroscopy. DENSA intercalates into the membrane at a high membrane/water partition coefficient (3.2.10(5)) and rapidly reorients from the outer to the inner layer in a first order process (k = 0.11 min-1, 37 degrees C, pH 7.4) leading to a steady-state distribution inner:outer layer of about 30:70. The activation energy of the fully reversible and symmetric flip process is about 110 kJ/mol. DIDS and various other established covalent and non-covalent inhibitors of anion transport via the erythrocyte anion exchanger, band 3 (AE 1), suppress the flip to a minimum of about 30-35% of the control. The flip is also inhibited by Cl- with a half maximal inhibitory concentration equal to that required for the inhibition of the exchange flux of ordinary anions via band 3. These findings indicate the involvement of a band 3 mediated (DIDS-sensitive) component of the flip and a DIDS-insensitive one, possibly involving, at least to some extent, simple transbilayer 'diffusion'. This latter component is stimulated by diamide, an SH oxidant known to increase the permeability of the membrane lipid domain of the erythrocyte. Alcohols (butanol, hexanol) accelerate both flip components. Papain treatment, known to inhibit 'ordinary' anion exchange, accelerates both flip and flop. The results suggest that band 3 protein, besides being a conventional transporter of anions, can act as a flippase translocating anionic, membrane-intercalated amphiphiles approaching the transporter from the lipid domain. The flippase mode of operation of band 3 must, however, differ in its mechanism from the conventional exchange mode.
 ...
PMID:Band 3, the anion exchanger of the erythrocyte membrane, is also a flippase. 817 17

The transbilayer movement of glycosphingolipids has been characterized in Golgi, ER, plasma, and model membranes using spin-labeled and fluorescent analogues of the monohexosylsphingolipids glucosylceramide and galactosylceramide and of the dihexosylsphingolipid lactosylceramide. In large unilamellar lipid vesicles, monohexosylsphingolipids underwent a slow transbilayer diffusion (half-time between 2 and 5 h at 20 degrees C). Similarly, the inward redistribution of these sphingolipids in the plasma membrane of the hepatocyte-like cell line HepG2 and of erythrocytes was slow. However, in rat liver ER and Golgi membranes, we found a rapid transbilayer movement of spin-labeled monohexosylsphingolipids (half-time of approximately 3 min at 20 degrees C), which suggests the existence of a monohexosylsphingolipid flippase. The transbilayer movement of glucosylceramide in the Golgi and the ER displayed a saturable behavior, was inhibited by proteolysis, did not require Mg-ATP, and occurs in both directions. Treatment with DIDS inhibited the flip-flop of glucosylceramide but not that of phosphatidylcholine. These data suggest that the transbilayer movement of monoglucosylceramide in the ER and in the Golgi involves a protein that could be distinct from that previously evidenced for glycerophospholipids in the ER. In vivo, transbilayer diffusion should promote a symmetric distribution of monohexosylsphingolipids which are synthesized in the cytosolic leaflet. This should allow glucosylceramide rapid access to the lumenal leaflet where it is converted to lactosylceramide. No significant transbilayer movement of lactosylceramide occurred in both artificial and natural membranes over 1 h. Thus, lactosylceramide, in turn, is unable to diffuse to the cytosolic leaflet and remains at the lumenal leaflet where it undergoes the subsequent glycosylations.
 ...
PMID:Transbilayer movement of monohexosylsphingolipids in endoplasmic reticulum and Golgi membranes. 1239 39