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)

Protein I is a neuron-specific, synaptic phosphoprotein highly localized on the surface of synaptic vesicles. We have recently isolated anti-Protein I IgG by affinity chromatography and shown that these antibodies inhibit specifically the phosphorylation of Protein I (Naito, S., and Ueda, T. (1981) J. Biol. Chem. 256, 10657-10663). In an effort to characterize Protein I-associated synaptic vesicles with respect to the types of neurotransmitters, we have now developed a procedure, using the affinity-purified anti-Protein I IgG, which allows immunoprecipitation of those synaptic vesicles which contain Protein I. The isolated vesicles are largely free of contamination from other intracellular organelles and plasma membranes. We present evidence that these vesicles isolated from bovine cortex are able to accumulate L-glutamate specifically in an ATP-dependent, temperature-dependent but Na-independent manner. Thus, the structurally similar aminoacid neurotransmitters aspartate and gamma-aminobutyric acid, as well as other neurotransmitters such as dopamine, norepinephrine, serotonin, acetylcholine, and glycine, failed to show a significant ATP-dependent uptake into these vesicles. Moreover, the ATP-dependent glutamate uptake was not inhibited effectively by glutamine, aspartate, or gamma-aminobutyric acid. The ATP-dependent glutamate uptake requires ATP hydrolysis; thus there was little accumulation of glutamate in the absence of ATP or Mg2+, or when ATP was replaced by an unhydrolyzable beta, gamma-methylene ATP analog. The glutamate uptake appears to be driven at least in part by a membrane potential generated by Mg2+-ATPase, similar to that of the catecholamine and serotonin uptakes into storage granules. These observations suggest that Protein I may be involved in some aspect of the function of glutamate-containing synaptic vesicles in the brain.
 ...
PMID:Adenosine triphosphate-dependent uptake of glutamate into protein I-associated synaptic vesicles. 613 88

We have shown that red blood cell (RBC) adenosine-5'-triphosphate (ATP) is better maintained and that there is less hemolysis and K+ leakage in hypotonic experimental additive solutions (EASs) containing glutamine and glutamine plus phosphate (Pi) than in the conventional additive solution Adsol during blood bank storage. The objective of this study was to determine if the beneficial effect produced in these media correlates with better preservation of RBC membrane properties including lipid content, phospholipid organization, aminophospholipid transport (flippase), and prothrombin converting activity. Aliquots of packed RBCs were stored in EASs containing adenine, glucose, sodium chloride, and mannitol, with 10 mmol/L glutamine (EAS 44) or with 10 mmol/L glutamine and 20 mmol/L Pi(EAS 45), or in Adsol. RBC membranes were studied after 0, 28, 42, and 84 days of storage, and vesicle membranes were studied after 84 days. RBC cholesterol and phospholipid content remained significantly greater (P < .01) in EASs than in Adsol. The degree of membrane vesiculation was more than 50% lower in EASs than in Adsol (P < .01). After 42 days of storage, the accessibility of phosphatidylethanolamine to phospholipases was approximately 1.5 times greater for Adsol and EAS 44 samples than for EAS 45 samples (43.5% v 28%). The rates of phosphatidylserine transport were 43% to 70% lower for stored cells but were not dependent on storage media. The amounts of bands 3 and 4.1 in the microvesicle membranes were not statistically different in any of the preparations. These results suggest that storage of RBCs in glutamine and Pi-medium better maintains ATP, lipid content, and phospholipid asymmetry and results in decreased vesiculation.
 ...
PMID:Glutamine- and phosphate-containing hypotonic storage media better maintain erythrocyte membrane physical properties. 869 18

Lipid transport is an essential process with manifest importance to human health and disease. Phospholipid flippases (P4-ATPases) transport lipids across the membrane bilayer and are involved in signal transduction, cell division, and vesicular transport. Mutations in flippase genes cause or contribute to a host of diseases, such as cholestasis, neurological deficits, immunological dysfunction, and metabolic disorders. Genome-wide association studies have shown that ATP10A and ATP10D variants are associated with an increased risk of diabetes, obesity, myocardial infarction, and atherosclerosis. Moreover, ATP10D SNPs are associated with elevated levels of glucosylceramide (GlcCer) in plasma from diverse European populations. Although sphingolipids strongly contribute to metabolic disease, little is known about how GlcCer is transported across cell membranes. Here, we identify a conserved clade of P4-ATPases from Saccharomyces cerevisiae (Dnf1, Dnf2), Schizosaccharomyces pombe (Dnf2), and Homo sapiens (ATP10A, ATP10D) that transport GlcCer bearing an sn2 acyl-linked fluorescent tag. Further, we establish structural determinants necessary for recognition of this sphingolipid substrate. Using enzyme chimeras and site-directed mutagenesis, we observed that residues in transmembrane (TM) segments 1, 4, and 6 contribute to GlcCer selection, with a conserved glutamine in the center of TM4 playing an essential role. Our molecular observations help refine models for substrate translocation by P4-ATPases, clarify the relationship between these flippases and human disease, and have fundamental implications for membrane organization and sphingolipid homeostasis.
 ...
PMID:Yeast and human P4-ATPases transport glycosphingolipids using conserved structural motifs. 3053 Apr 92