# 6.6: Generating gradients: using coupled reactions and pumps

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Both carriers and channels allow the directional movement (net flux) of molecules across a membrane, but only when a concentration gradient is present. If a membrane contains active channels and carriers (as all membranes do), without the input of energy eventually concentration gradients across the membrane will disappear (disperse). The [molecule] outside will become equal to [molecule] inside. Yet, when we look at cells we find lots of concentration gradients, which raises the question, what produces and then maintains these gradients.

The common sense answer is that there must be molecules (proteins) that can transport specific types molecules across a membrane and against their concentration gradient. We will call these types of molecule pumps and write the reaction it is involved in as:

[Molecule]low concentration + pump ⟷ [Molecule]high concentration +pump

As you might already suspect this is a thermodynamically unfavorable reaction. Like a familiar macroscopic pump, it will require the input of energy. We will have to “plug in” our molecular pump into some source of energy. What energy sources are available to biological systems? Basically we have two choices: the system can use electromagnetic energy, that is light, or it can use chemical energy. In a light-driven pump, there is a system that captures (absorbs) light; the absorbance of light (energy) is coupled to the pumping system. Where the pump is driven by a chemical reaction, the thermodynamically favorable reaction is often catalyzed by the pump itself and that reaction is coupled to the movement of a molecule against its concentration gradient. An interesting topological point is that for a light or chemical reaction driven pump to work to generate a concentration gradient, all of the pump molecules within a membrane must be oriented in the same direction. If the pumps were oriented randomly there will be no overall flux (the molecules would move in both directions) and no gradient would develop.

Chemical-reaction driven pumps are also oriented within membranes in the same orientation. A number of chemical reactions can be used to drive such pumps and these pumps can drive various reactions (remember reactions can move in both directions). One of the most common ones involve the movement of energetic electrons through a membrane-bound, protein-based “electron transport” system, leading to the creation of an H+ electrochemical gradient. The movement of H+ down its concentration gradient, through the pump, drives the synthesis of ATP. The movement of H+ from the side of the membrane with relatively high [H+] to that of relatively low [H+] is coupled to the ATP synthesis through the membrane bound ATP synthase enzyme:

[H+]high concentration-outside + adenosine diphosphate (ADP) (intracellular) + phosphate (intracellular) ⇌ adenosine triphosphate (ATP) (intracellular) + H20 (intracellular) + [H+]low concentration-inside.

This reaction can run in reverse, in which case ATP is hydrolyzed to form ADP and phosphate, and H+ is moved against is concentration gradient, that is, from a region of low concentration to a region of higher concentration.

[H+]low concentration-inside + adenosine triphosphate (ATP) (intracellular) + H20 (intracellular) ⇌ adenosine diphosphate (ADP) (intracellular) + phosphate (intracellular) + [H+]high concentration-inside.

In general, by coupling a ATP hydrolysis reaction to the pump, the pump can move molecules from a region of low concentration to one of high concentration, a thermodynamically unfavorable reaction.