Molecules Move Spontaneously from Regions of High Free Energy to Regions of Lower Free Energy
The majority of biochemicals do not pass readily through a phospholipid bilayer. Transport of this molecular majority requires a protein pathway across the biomembrane. Also needed is a force causing movement along the pathway.
Before elaborating on membrane proteins as pathways through the lipid bilayer, the energy factors that drive the transport are considered.Objects fall spontaneously because of gravity. T'his is a manifestation of the principle that movement occurs to minimize the potential energy of the object. Indeed, all change in the universe (at scales greater than the subatomic particles) occurs to minimize the potential energy, also called the free energy, of the system. The movement of molecules is strongly affected by forces such as concentration, pressure (both part of chemical potential), and voltage (electrical potential). Molecules move spontaneously from a region of higher concentration to lower concentration, from higher to lower pressure, and from higher to lower electrical potential. Each of these factors—concentration, pressure, and electrical potential—is a source of free energy. The transport of a molecule does not depend necessarily on any one factor; rather, the sum of all the free energy contributions is the determinant of transport. The sum of all the free energy contributions on a substance is usually expressed on a permole basis as the electrochemical potential. The electrochemical potential is the free energy of the substance, from all sources, per mole of the substance.
hi order for spontaneous transport to occur, there must be a difference in the electrochemical potential of the substance between two regions. The two regions are usually two compartments separated by a membrane. This difference in electrochemical potential is called the driving force. 'Fypically, students have little difficulty understanding the direction of spontaneous flow as long as only one factor contributes to the electrochemical potential, pressure, or concentration or the voltage.
However, understanding physiological transport, both across cells and across tissues, requires an understanding of the contribution of each factor to the driving force. For example, the flow of fluid from the capillaries of the vascular system depends on the balance between both the hydrostatic pressure difference and the concentration difference of solutes (osmotic pressure) across the capillary. Similarly, movement of Na’ and Kf ions across the plasma membrane of nerve cells depends on the driving forces contributed by both voltage differences and ion concentration differences across the membrane.Material moves spontaneously from regions of high electrochemical potential to low electrochemical potential. Such transport is called diffusion or passive transport. Net movement of material (i.e., diffusion) stops when the electrochemical difference between regions equals zero. The stale al which the free energy or the electrochemical potential difference is zero is called equilibrium. Equilibrium means “balance,” not equality. Equilibrium is reached when the free energy (electrochemical potential) is balanced; the value on one side is the same as the other. In most cases the source of the free energies on the two sides never becomes equal; the concentrations, the pressure, and the voltages remain different, but their differences “balance out” so that the sum of the free energy differences is zero.
Equilibrium is a particularly important concept because it describes the state toward which change occurs if no work is put into the system. Once the system reaches equilibrium, no further net change occurs unless some work is done on the system. The words “net change” are important. Molecules at equilibrium still move and exchange places, but as much goes in one direction as in the other, so there is no net flow of material.
If the cell requires material to move from low to high electrochemical potential (i.e., in the direction away from equilibrium), thus increasing the difference in free energy between two regions, then some driving force, some work, most be provided by some other decrease in free energy. This type of transport is active transport. Active transport uses proteins that combine transport and reaction coupling functions; the protein couples the “uphill” movement of material to a “downhill” reaction such as ATP hydrolysis.