Facilitated diffusion (also known as facilitated transport) is a form of passive transport across a biological membrane in which a transporter protein facilitates (or mediates or catalyzes) the movement of an otherwise membrane-impermeant molecule or ion across the plasma membrane down its concentration or electrochemical gradient. The transport proteins responsible for this function are referred to as facilitative transporters or uniporters, examples of which include the ubiquitous glucose transporters (GLUT family), a variety of amino acid transporters, facilitative urea transporters, and others. Collectively, these transporters perform many essential cellular and organismal functions. In facilitated diffusion, the direction of transport is always down a concentration gradient from one side of the membrane where the substrate concentration is high to the other side of the membrane where the concentration is lower. The cartoon (animation) shown below is a simplified conceptual representation of the workings of a typical facilitative transporter.
Animated Figure 1. The alternating access model describes a general mechanism for facilitative transporters.
Facilitative transporters mediate the transport of membrane-impermeant solutes down a concentration gradient across biological membranes. Facilitated diffusion is a form of passive transport and, therefore, the direction of transport is always down a concentration gradient. The transport cycle can be described by the alternating access model. The cartoon (animation) shown here is a simplified conceptual representation of the workings of a typical facilitative transporter. See text for details.
The alternating access model describes a general mechanism of transport for carrier proteins
A general model that is used to describe the mechanism of transport for many transport proteins is the alternating access model (see Animated Figure 1). According to the alternating access model, the substrate binding site of a transport protein is alternately exposed to one or the other side of the membrane such that at no time is there an open and unrestricted permeation pathway through the transporter connecting the two fluid compartments separated by the membrane. It is postulated that binding of the substrate to its binding site induces a transporter conformation referred to as the occluded state. The occluded state refers to a transporter conformation in which the substrate binding site is exposed neither to one or the other side of the membrane. Following the occluded state, additional conformational changes expose the substrate to the other side. Dissociation of the substrate from the binding site is followed by the reorientation of the binding site to the original membrane surface such that the cycle can be repeated for as long as substrate molecules are present and that there is a substrate concentration gradient across the membrane.
Direction of transport is determined by the substrate concentration gradient
It is important to emphasize that a facilitative transporter is a passive transporter. It translocates its substrate down a concentration gradient from one side of the membrane where the substrate concentration is high to the other side of the membrane where the concentration is lower. Under most physiological conditions, the direction of the concentration gradient of a given substrate remains the same. For example, in most body cells, after glucose is transported into the cell by the glucose transporter, it is converted to glucose-6-phosphate, which can then participate in various metabolic pathways of the cell. As glucose-6-phosphate is not a substrate of the glucose transporter, this conversion essentially creates an infinite glucose concentration gradient. Therefore, given the plasma and interstitial fluid glucose concentration of around 5 mM, the glucose concentration gradient always favors the transport of glucose into the cell by the glucose transporters. However, if the substrate concentration gradient is reversed (physiologically or experimentally), the transporter direction of operation will also be reversed to ensure transport down a concentration gradient. If the substrate concentration is the same on both sides of the membrane, a facilitative transporter will be in equilibrium and can no longer achieve net substrate transport from one side to the other. Therefore, the direction of transport is a function of the substrate concentration gradient. The role of the facilitative transporter is to provide a translocation pathway through the membrane.
Facilitative transporters represent several gene families in the human genome
Numerous additional examples of facilitative transporters can be found in the human genome. For a complete of list of facilitative transport proteins found in the human genome, please visit the Human Genome Organization (http://www.hugo-international.org/) nomenclature page (http://www.genenames.org/).
Posted: Monday, January 24, 2011 Last updated: Thursday, January 7, 2016