Gene/Protein Disease Symptom Drug Enzyme Compound
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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.
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PMID:Band 3, the anion exchanger of the erythrocyte membrane, is also a flippase. 817 17

In pursuit of the characterization of the recently discovered flippase mode of operation of the anion transporter (band 3, AE1) of the human erythrocyte membrane, the transbilayer translocation (flip) of a fluorescently labeled, membrane-intercalated long-chain alkyl phosphate, 10-(alpha-napthyl)-1-decyl-phosphate (NDP) was investigated. In contrast to the alkyl sulfonates and esters of phosphatidic acid studied as yet, NDP moves exclusively via band 3. NDP is, however, dephosphorylated at the inner membrane surface by a cytoplasmic phosphatase likely to interact specifically with endofacial membrane structures of the erythrocyte. This phosphatase shares characteristic inhibitor sensitivities with protein tyrosine phosphatases present in the erythrocyte interior. Vanadate as an inhibitor of NDP dephosphorylation provided a means to study the kinetic properties and patterns of inhibition (by inhibitors of anion exchange) and stimulation (by proteolysis of band 3 and aliphatic alcohols) of the flip of NDP. NDP is also an inhibitor of the exchange of hydrophilic anions via band 3, while hydrophilic anions interfere with the flip of NDP. The results are compared with the characteristics of the flip, via Band 3, of other amphiphilic anions and of the exchange of hydrophilic anions. Attempts are presented to understand the low flip rate of long-chain amphiphilic anions on the basis of their molecular properties and the thermodynamics of the "transition state" of the flip process.
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PMID:Band 3-mediated flip-flop and phosphatase-catalyzed cleavage of a long-chain alkyl phosphate anion in the human erythrocyte membrane. 974 99

Synthetic high affinity peroxisome proliferator-activated receptor (PPAR) agonists are known, but biologic ligands are of low affinity. Oxidized low density lipoprotein (oxLDL) is inflammatory and signals through PPARs. We showed, by phospholipase A(1) digestion, that PPARgamma agonists in oxLDL arise from the small pool of alkyl phosphatidylcholines in LDL. We identified an abundant oxidatively fragmented alkyl phospholipid in oxLDL, hexadecyl azelaoyl phosphatidylcholine (azPC), as a high affinity ligand and agonist for PPARgamma. [(3)H]azPC bound recombinant PPARgamma with an affinity (K(d)((app)) approximately 40 nm) that was equivalent to rosiglitazone (BRL49653), and competition with rosiglitazone showed that binding occurred in the ligand-binding pocket. azPC induced PPRE reporter gene expression, as did rosiglitazone, with a half-maximal effect at 100 nm. Overexpression of PPARalpha or PPARgamma revealed that azPC was a specific PPARgamma agonist. The scavenger receptor CD36 is encoded by a PPRE-responsive gene, and azPC enhanced expression of CD36 in primary human monocytes. We found that anti-CD36 inhibited azPC uptake, and it inhibited PPRE reporter induction. Results with a small molecule phospholipid flippase mimetic suggest azPC acts intracellularly and that cellular azPC accumulation was efficient. Thus, certain alkyl phospholipid oxidation products in oxLDL are specific, high affinity extracellular ligands and agonists for PPARgamma that induce PPAR-responsive genes.
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PMID:Oxidized alkyl phospholipids are specific, high affinity peroxisome proliferator-activated receptor gamma ligands and agonists. 1127 49