The glycine transporter type 1 (GlyT1) has emerged as a key novel target for the treatment of schizophrenia. We have recently discovered and developed [^11^C]RO5013853 as a novel positron emission tomography tracer for GlyT1 for which a reliable fiveβstep synthetic route was established. The incorpo
A Maxwell's Demon Type of Membrane Transport: Possibility for Active Transport by ABC-Type Transporters?
β Scribed by ULRICH HOPFER
- Publisher
- Elsevier Science
- Year
- 2002
- Tongue
- English
- Weight
- 188 KB
- Volume
- 214
- Category
- Article
- ISSN
- 0022-5193
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β¦ Synopsis
ATP-binding-cassette (or ABC)-type transporters constitute one of the largest family of membrane transporters in nature. Many of its members move substrates &&actively'', i.e. in an ATP-dependent manner against an electrochemical gradient. No consensus is available about the mechanism. Therefore, a novel class of transport mechanisms is proposed based on Maxwell's demon idea. This transport mechanism consists of a gated pore that selectively opens for substrates from one, but not the other side. Thermoenergy (Brownian motion) would su$ce for substrate translocation across the membrane; energy for synchronizing gate opening with substrate arrival would come from ATP hydrolysis. Simulations demonstrate that such a mechanism would be thermodynamically and kinetically feasible. It exhibits &&active'', unidirectional transport, saturation, and other typical features of protein-catalysed reactions. It also shows pore behavior with charged substrates moving under the in#uence of electrical potentials. Its e$ciency depends on a di!usion time constant of the substrate in solution that is slower than the transit time through the membrane, a situation that can realistically be achieved at millimolar or lower substrate concentrations. Features of the novel mechanism that di!er signi"cantly from P-or F-type ATPases are: (1) transport cannot be run in &&reverse'' to synthesize ATP even if su$cient energy is available in the gradient of the transported solute and (2) unidirectional and net substrate #uxes through the transporter diverge with increasing substrate concentration.
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