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 EI-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 Ca2+-ATPase or Na+/K--ATPase. (C) 2001 Elsevier Science B.V. All rights reserved.