Lipid-protein interactions and Ca2+-ATPase function

Lee, A G; Starling, A P; Ding, Jian; East, J. Malcolm; Wictome, M

doi:10.1042/bst0220821

Cited by 17 publications

(13 citation statements)

References 5 publications

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“…In mitochondrial PL, elevated levels of 22:6 appear to be associated with high flux capacity through the respiratory chain. In sarcoplasmic reticulum, the presence of additional 22:6 stimulates capacity for calcium pumping and may be responsible for increasing the net Ca 2+ /ATP coupling ratio (Infante, 1987;Lee et al, 1994). Consequently, extremely high contents of 22:6 have been found in the membranes of highperformance muscles like hummingbird flight muscle and rattlesnake shaker muscle (Infante et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Relationship between n-3 PUFA content and energy metabolism in the flight muscles of a migrating shorebird: evidence for natural doping

Maillet

Weber

2007

Journal of Experimental Biology

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SUMMARY During their fall migration from the Arctic to South America, semipalmated sandpipers Calidris pusilla stop in the Bay of Fundy (east coast of Canada) before flying non-stop for ∼4500 km across the ocean. Refueling birds double their body mass by feeding on Corophium volutator, an amphipod containing high amounts of n-3 polyunsaturated fatty acids (n-3 PUFA), particularly eicosapentaenoic (20:5) and docosahexaenoic acid (22:6). In mammals, high dietary intake of n-3 PUFA is known to increase capacity for oxidative metabolism. Therefore, we hypothesized that tissue incorporation of n-3 PUFA would be associated with increases in the activity of key muscle enzymes to upregulate energy metabolism for prolonged exercise. Birds were collected at various stages of fat loading to monitor changes in lipid composition and flight muscle enzymes simultaneously. Enzymes were measured to assess oxidative capacity [citrate synthase (CS)],β-oxidation [carnitine palmitoyl transferase (CPT) and 3-hydroxyacyl dehydrogenase (HOAD)] and glycolytic capacity [lactate dehydrogenase (LDH)]. Changes in the fatty acid composition of muscle membranes (phospholipids) and fuel reserves (neutral lipids) were measured separately to distinguish between membrane-related and systemic effects of n-3 PUFA. Results show that muscle CS and HOAD are stimulated during refueling and that their activities are correlated with n-3 PUFA content in phospholipids (22:6 for CS, 20:5 for HOAD)and in neutral lipids (20:5 for CS). This suggests that 20:5 and 22:6 have different effects on energy metabolism and that they act via changes in membrane structure and systemic mechanisms. CPT and LDH did not change during refueling, but LDH activity was significantly related to the n-3 PUFA content of fuel reserves. This study shows that oxidative capacity increases rapidly during refueling and supports the idea that dietary n-3 PUFA are used as molecular signals to prime flight muscles of some long-distance migrants for extreme exercise.

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Section: Discussionmentioning

confidence: 99%

Relationship between n-3 PUFA content and energy metabolism in the flight muscles of a migrating shorebird: evidence for natural doping

Maillet

Weber

2007

Journal of Experimental Biology

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“…Four acidic residues have been identified in the ATPase whose mutation disrupts the high-affinity binding of Ca# + from the cytoplasmic side of the membrane. These residues are located in putative transmembrane helices 4, 5, 6 and 8 ; the two high-affinity binding sites for Ca# + are presumed to be located in a channellike structure made up of these four helices [25,26]. Up to four extra acidic residues are then needed for the luminal pair of sites.…”

Section: Discussionmentioning

confidence: 99%

Stimulation of the Ca2+-ATPase of sarcoplasmic reticulum by disulfiram

Starling

East

Lee

1996

Biochemical Journal

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Disulfiram [bis(diethylthiocarbamoyl)disulphide] has been found to stimulate reversibly the Ca(2+)-ATPase of skeletal muscle sarcoplasmic reticulum. At pH 7.2, 2.1 mM ATP and 25 degrees C, ATPase activity was found to double on addition of 120 microM disulfiram. Stimulation fitted to binding of disulfiram at a single site with a Kd of 61 microM. Disulfiram had no effect on the Ca2+ affinity of the ATPase or on the rate of phosphorylation of the ATPase by ATP, but increased the rate of dissociation of Ca2+ from the phosphorylated ATPase (the transport step) and increased the rate of dephosphorylation of the phosphorylated ATPase. It also decreased the level of phosphorylation of the ATPase by Pi, consistent with a 7.5-fold decrease in the equilibrium constant of the phosphorylated to non-phosphorylated forms (E2PMg/E2PiMg) at 80 microM disulfiram. Disulfiram had no significant effect on the concentration of ATP resulting in stimulation of ATPase activity, suggesting that it does not bind to the empty nucleotide-binding site on the phosphorylated ATPase. Studies of the effects of mixtures of disulfiram and jasmone (another molecule that stimulates the ATPase) suggest that they bind to separate sites on the ATPase.

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“…The site-directed mutagenesis experiments of Clarke et al [11,15] showed that the high-affinity Ca# + -binding sites are located in the trans-membrane region of the ATPase, between putative trans-membrane α-helices M4, M5, M6 and M8, each of which contains one negatively charged residue. It has been proposed that helices M4, M5, M6 and M8 are packed in a square array, making a channel-like structure in which the two Ca# + ions bind with high affinity, one above the other [14,16]. Phosphorylation of the ATPase, with transfer of the two bound Ca# + ions from the pair of high-affinity sites to a second pair of low-affinity sites, presumably involves a change in the packing of these four helices.…”

Section: Methodsmentioning

confidence: 99%

“…Phosphorylation of the ATPase, with transfer of the two bound Ca# + ions from the pair of high-affinity sites to a second pair of low-affinity sites, presumably involves a change in the packing of these four helices. It has also been suggested that the packing of the four helices changes during the Ca# + binding process, the initial E1 conformation of the ATPase only possessing a single Ca# + ion binding site, with binding of the first Ca# + ion leading to a change in the packing of the helices and the creation of the second Ca# + ion binding site [16,17].…”

Section: Methodsmentioning

confidence: 99%

Mutational analysis of trans-membrane helices M3, M4, M5 and M7 of the fast-twitch Ca2+-ATPase

Adams

East

Lee

et al. 1998

Biochemical Journal

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Mutational analysis of trans-membrane helices M3, M4, M5 and M7 of the Ca2+-ATPase revealed a novel phenotypic variant, M4 [Y295A (the one-letter symbols are used for amino acid residues throughout)], displaying an increased affinity for Pi and decreased affinity for MgATP, while retaining the ability to translocate Ca2+ ions across the endoplasmic reticulum membrane. The properties of this mutant suggest that the E1-E2 equilibrium is shifted towards E2, and indicate a key role for this aromatic residue (Y295) at the end of trans-membrane helix M4. A mutant containing three amino acid residue substitutions at the end of the seventh trans-membrane helix, M7 (F834A, F835A, T837F), showed a complete loss of ATPase activity and a reduced ability to phosphorylate with Pi, although MgATP-initiated phosphorylation was unaffected. The observation that single mutations in this cluster of residues had no effect on Ca2+ transport suggests that correct anchoring of the helix at the lipid-water interface by these aromatic residues is important in the functioning of the ATPase. Mutation of polar residues in helix M3 did not affect inhibition of the ATPase by thapsigargin, thapsivillosin A or t-butyl hydroquinone, suggesting that hydrogen-bonding partners for the essential -OH groups on these inhibitors lie elsewhere in the ATPase.

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Lipid-protein interactions and Ca2+-ATPase function

Cited by 17 publications

References 5 publications

Relationship between n-3 PUFA content and energy metabolism in the flight muscles of a migrating shorebird: evidence for natural doping

Relationship between n-3 PUFA content and energy metabolism in the flight muscles of a migrating shorebird: evidence for natural doping

Stimulation of the Ca2+-ATPase of sarcoplasmic reticulum by disulfiram

Mutational analysis of trans-membrane helices M3, M4, M5 and M7 of the fast-twitch Ca2+-ATPase

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