Facilitated Diffusion and Active Transport
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You should understand the basic structure of the plasma membrane, including the phospholipid bilayer and the role of integral proteins, and be familiar with the concept of a concentration gradient as established in the previous lecture on osmosis.
Why this matters
Cells cannot rely on simple diffusion alone to maintain the precise internal environment required for life.
While small, non-polar molecules can slip through the lipid bilayer, the vast majority of essential substances—such as glucose, amino acids, and ions—are either too large or too polar to cross passively. Without specific mechanisms to move these molecules against their gradients or to regulate their entry, cells would be unable to maintain homeostasis, generate energy, or respond to external signals. This lecture explores the two primary strategies cells use to overcome these barriers: facilitated diffusion, which uses protein channels to speed up passive movement, and active transport, which expends energy to move substances uphill. Understanding these processes is fundamental to grasping how nerve impulses are generated, how nutrients are absorbed in the gut, and how drugs are delivered to their targets.
The Gatekeepers: Why Proteins Are Necessary
Imagine the cell membrane as a thick, waxy wall. If you want to move a tiny, oil-soluble molecule like oxygen across this wall, it can simply dissolve into the wax and drift to the other side. This is simple diffusion. However, if you want to move a large, water-loving molecule like glucose, or a charged ion like sodium, the waxy wall is an impenetrable barrier. The hydrophobic interior of the bilayer repels these polar and charged species. Therefore, the cell must build specific doors and pumps into this wall. These are the membrane transport proteins.
There are two main types of these proteins. The first type acts like a door that opens only when the right key is present. This is a channel or carrier protein that allows molecules to flow down their concentration gradient, from high to low concentration. Because the energy comes from the gradient itself, this process is passive, but it is much faster than simple diffusion because the protein provides a hydrophilic pathway through the hydrophobic core. This is called facilitated diffusion. The second type acts like a pump. It uses energy, usually in the form of ATP, to move molecules against their concentration gradient, from low to high. This is active transport. The key distinction is the direction of movement relative to the gradient and the requirement for metabolic energy. Without these protein-based mechanisms, cells would be unable to accumulate nutrients or expel waste products efficiently, leading to a rapid loss of homeostasis and cell death.
Facilitated Diffusion: Carrier Proteins and Channels
Facilitated diffusion is a passive process, meaning it does not require direct input of metabolic energy such as ATP. Instead, it relies on the kinetic energy of the molecules and the potential energy stored in the concentration gradient. The rate of facilitated diffusion is governed by the same principles as simple diffusion, but with a crucial modification: the permeability coefficient is significantly higher due to the presence of specific transporters. The net flux \( J \) can still be described by Fick's first law, but the effective diffusion coefficient \( D \) is enhanced by the protein-mediated pathway. However, unlike simple diffusion, which is linear with respect to concentration difference, facilitated diffusion exhibits saturation kinetics. This is because there is a finite number of transporter proteins in the membrane. Once all transporters are occupied by substrate molecules, the rate of transport reaches a maximum velocity, \( V_{\max} \), and cannot increase further, even if the concentration gradient is increased. This behaviour is analogous to enzyme kinetics, described by the Michaelis-Menten equation, where the transporter acts as an enzyme and the transported molecule as the substrate.
There are two main classes of facilitated diffusion proteins: channels and carriers. Channel proteins form hydrophilic pores that span the membrane. They are typically selective for specific ions, such as potassium or chloride channels. The flow through channels is very rapid, often limited only by the physical rate of diffusion through the pore. Carrier proteins, on the other hand, bind to their specific substrate molecule and undergo a conformational change to move it across the membrane. This process is slower than channel-mediated transport but allows for greater specificity and regulation. An example is the glucose transporter GLUT1, which facilitates the uptake of glucose into red blood cells. The selectivity of these proteins is crucial; GLUT1 carries glucose but hardly any fructose, and a sodium channel will not allow potassium ions to pass freely. This specificity ensures that the cell maintains the correct internal composition of ions and metabolites.
Active Transport: Primary and Secondary Mechanisms
Active transport is the movement of molecules across a membrane against their electrochemical gradient. This process requires energy because it is thermodynamically unfavorable. There are two main types of active transport: primary and secondary. Primary active transport directly uses the energy from the hydrolysis of ATP to drive the conformational changes in the transport protein. The most famous example is the sodium-potassium pump, or Na+/K+-ATPase. This pump moves three sodium ions out of the cell and two potassium ions into the cell for every molecule of ATP hydrolyzed. This creates and maintains a high concentration of sodium outside the cell and a high concentration of potassium inside, which is essential for maintaining the resting membrane potential and cell volume. The energy from ATP hydrolysis is coupled to the transport process, allowing the pump to work against the steep concentration gradients of these ions.
Secondary active transport, also known as coupled transport, uses the energy stored in the electrochemical gradient of one ion to drive the transport of another molecule against its gradient. It does not directly use ATP but relies on the gradient established by primary active transport. There are two forms: symport and antiport. In symport, both molecules move in the same direction. For example, the sodium-glucose cotransporter (SGLT1) in the intestinal epithelium uses the inward flow of sodium ions down their electrochemical gradient to drive the uphill transport of glucose into the cell. In antiport, the molecules move in opposite directions. An example is the sodium-calcium exchanger in cardiac muscle cells, which uses the inward flow of sodium to expel calcium ions from the cell. The energy for secondary active transport is derived from the potential energy of the ion gradient, which was originally established by primary active transport. This indirect use of energy allows cells to regulate the transport of many different substances using a single energy source, ATP.
Electrochemical Gradients and Membrane Potential
For ions, the driving force for transport is not just the concentration gradient but the electrochemical gradient, which includes both the chemical concentration difference and the electrical potential difference across the membrane. The membrane potential, \( V_m \), is the voltage difference between the inside and outside of the cell. For most animal cells, the inside is negative relative to the outside, typically around -70 mV. This negative interior attracts cations (positive ions) and repels anions (negative ions). The electrochemical potential difference, \( \Delta \mu \), for an ion of valence \( z \) is given by the sum of the chemical potential difference and the electrical potential difference. The chemical component is related to the concentration ratio, while the electrical component is proportional to the membrane potential and the charge of the ion. The direction of net ion flow depends on the balance between these two forces. If the electrical force favours movement into the cell and the chemical force favours movement out, the net direction depends on which force is stronger. The equilibrium potential for a specific ion, \( E_{ion} \), is the membrane potential at which the electrical and chemical forces are exactly balanced, resulting in no net flow of that ion. This is calculated using the Nernst equation, which relates the equilibrium potential to the ratio of extracellular to intracellular ion concentrations.
Understanding the electrochemical gradient is critical for understanding how cells maintain their resting potential and how they generate action potentials. The sodium-potassium pump contributes directly to the membrane potential by moving three positive charges out and two positive charges in, creating a net outward current. This electrogenic effect helps maintain the negative interior. Additionally, the pump establishes the concentration gradients that drive secondary active transport and passive ion flow through channels. The interplay between active transport, passive diffusion, and the resulting membrane potential is a dynamic process that requires constant energy input to maintain. Disruption of this balance, such as by inhibiting the sodium-potassium pump, leads to a loss of membrane potential, swelling of the cell, and eventually cell death. Thus, active transport is not just a mechanism for moving molecules but a fundamental regulator of cellular electrical activity and volume.
The concept
Diffusion and osmosis
Passive movement of molecules down a gradient.
A common misconception is that facilitated diffusion is "active" because it involves proteins. It is not. It is passive because it moves down the gradient and does not consume ATP. The protein merely lowers the activation energy for crossing the membrane, similar to how an enzyme lowers the activation energy for a reaction, but the thermodynamic direction is still downhill. Confusing this with active transport leads to errors in predicting the direction of net flux when gradients change. C
Worked example
Problem. A cell has an intracellular sodium concentration of 10 \(\mathrm{mM}\) and an extracellular sodium concentration of 140 \(\mathrm{mM}\). The membrane potential is -65 \(\mathrm{mV}\). Calculate the electrochemical driving force for sodium ions entering the cell. Assume the temperature is 37 °C (310 \(\mathrm{K}\)). Use \( R = 8.314\ \mathrm{J\,mol^{-1}\,K^{-1}} \) and \( F = 96485\ \mathrm{C\,mol^{-1}} \). The electrochemical potential difference \( \Delta \mu_{Na^+} \) is given by \( \Delta \mu_{Na^+} = RT \ln \left( \frac{[Na^+]_{in}}{[Na^+]_{out}} \right) + zF V_m \), where \( z = +1 \) for sodium.
- Identify the given values: \( [Na^+]_{in} = 10\ \mathrm{mM} \), \( [Na^+]_{out} = 140\ \mathrm{mM} \), \( V_m = -65\ \mathrm{mV} = -0.065\ \mathrm{V} \), \( T = 310\ \mathrm{K} \), \( z = +1 \).
- Calculate the chemical potential term: \( RT \ln \left( \frac{10}{140} \right) = (8.314)(310) \ln (0.0714) \). First, \( \ln (0.0714) \approx -2.64 \). Then, \( (8.314)(310)(-2.64) \approx -6800\ \mathrm{J\,mol^{-1}} \).
- Calculate the electrical potential term: \( zF V_m = (1)(96485)(-0.065) \approx -6272\ \mathrm{J\,mol^{-1}} \).
- Sum the two terms to find the total electrochemical potential difference: \( \Delta \mu_{Na^+} = -6800 + (-6272) = -13\,070\ \mathrm{J\,mol^{-1}} \).
- Interpret the sign: A negative \( \Delta \mu \) indicates that the movement of sodium from outside to inside is energetically favourable (downhill). The magnitude is approximately 13.1 \(\mathrm{kJ\,mol^{-1}} \).
Units check. The terms \( RT \ln \) and \( zF V_m \) both yield units of \( \mathrm{J\,mol^{-1}} \), which is consistent with molar energy.
Three quick tests
- What is the key difference between facilitated diffusion and active transport in terms of energy usage?
Answer
Facilitated diffusion is passive and moves down the gradient without ATP, while active transport moves against the gradient and requires energy (ATP or ion gradient). - Why does facilitated diffusion exhibit saturation kinetics?
Answer
Because there is a finite number of transporter proteins in the membrane. Once all are occupied, the rate reaches a maximum and cannot increase further. - How does the sodium-potassium pump contribute to the membrane potential?
Answer
It is electrogenic, moving three positive charges out and two in, creating a net outward current that helps maintain the negative interior potential.
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Every lecture and every concept in this unit, with prerequisites and threads.
Lecture notes checked line by line by the editor; every number in the worked example was recomputed.
Concepts cited: T-028 · Threads: regulation, systems