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Talk Abstract
A Kinetic Model for Secondary Active Transport

Donald Loo
Department of Physiology
UCLA School of Medicine
Los Angeles, CA 90075-1751

Cotransporters are membrane proteins which use ion (Na+, H+) electrochemical potential gradients to accumulate substrates (nutrients, neurotransmitters, osmolytes and ions) in cells. The archetypical example is the Na+/glucose cotransporter (SGLT). Electrophysiological and radioactive tracer studies indicate that the function of SGLT can be described by a 6-state ordered kinetic model where Na+, sugar and membrane voltage modulate, via protein conformational changes, the accessibility of the transporter from one side of the membrane to the other. On the external membrane surface, two Na+ ions bind to SGLT before the sugar molecule. The fully-loaded protein undergoes a conformational change, and sugar and Na+ are subsequently released in the internal membrane surface. The cycle is repeated upon restoration of the protein to the external surface. This model, which is based on the alternating access hypothesis, can account for the experimental observations on SGLT and have been extended to many other cotransporters. Evidence supporting the alternating access model have recently been obtained from experiments where cotransporter activity and protein conformational changes are simultaneously monitored by electrophysiological and optical methods.

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1998-1999 Mathematics in Biology