Slippage and uncoupling in P-type cation pumps; implications for energy transduction mechanisms and regulation of metabolism.
P-type ATPases couple scalar and vectorial events under optimized states. A number of procedures and conditions lead to uncoupling or slippage. A key branching point in the catalytic cycle is at the cation-bound form of E(1)-P, where isomerization to E(2)-P leads to coupled transport, and hydrolysis leads to uncoupled release of cations to the cis membrane surface. The phenomenon of slippage supports a channel model for active transport. Ability to occlude cations within the channel is essential for coupling. Uncoupling and slippage appear to be inherent properties of P-type cation pumps, and are significant contributors to standard metabolic rate. Heat production is favored in the uncoupled state. A number of disease conditions, include ageing, ischemia and cardiac failure, result in uncoupling of either the Ca(2+)-ATPase or Na(+)/K(+)-ATPase.
Berman
M C
MC
Division of Chemical Pathology, Health Sciences Faculty, University of Cape Town, Observatory 7925, Cape Town, South Africa. mervyn@chempath.uct.ac.za
D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000375:Aging; D000818:Animals; D001665:Binding Sites; D001693:Biological Transport, Active; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000737:chemistry / Q000378:metabolism; D002413:Cations, Divalent; D002462:Cell Membrane / Q000201:enzymology; D004734:Energy Metabolism; D004912:Erythrocytes / Q000378:metabolism; D006801:Humans; D008563:Membrane Lipids / Q000378:metabolism; D008956:Models, Chemical; D018482:Muscle, Skeletal / Q000378:metabolism; D010944:Plants; D006180:Proton-Translocating ATPases / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013816:Thermodynamics; D015003:Yeasts
D002413:Cations, Divalent; D008563:Membrane Lipids; D000251:Adenosine Triphosphatases; D006180:Proton-Translocating ATPases; D000252:Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium