Active transport moves molecules against their gradient. This requires energy, either directly from ATP (primary) or from another ion gradient (secondary).
Five ways across a membrane
Transport
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Passive: down the gradient, no ATP Active: against the gradient, costs energy Bulk transport by vesicle The membrane
The one question that sorts themAsk which way relative to the gradient. Down the gradient is passive and free, whether or not a protein helps. Against the gradient always costs energy, and the only argument is whether the cell pays with ATP directly or spends a gradient it already built.
Why secondary active is still activeThe cotransporter itself uses no ATP. But the sodium gradient it rides was built by the Na⁺/K⁺-ATPase, which does. Stop that pump and secondary active transport stops within minutes, which is exactly how ouabain and digoxin work.
Saturation is the tellAnything that uses a protein has a finite number of them, so its rate plateaus like an enzyme, complete with a Km-equivalent. Simple diffusion has nothing to saturate, so its rate rises linearly with the gradient forever. A graph that plateaus means a protein is involved.
Two questions answer every transport problem: is a protein involved, and is it moving with or against the gradient. Protein plus with-the-gradient is facilitated diffusion; protein plus against is active, and then you only have to say who pays.
Primary Active Transport
The pump uses ATP directly. Classic example: Na+/K+ ATPase.
Each cycle:
Pump binds 3 Na+ from inside + 1 ATP.
ATP hydrolysis phosphorylates the pump; it changes shape and expels 3 Na+ to outside.
Pump binds 2 K+ from outside.
Phosphate is released; the pump changes shape again and releases 2 K+ inside.
Net result per ATP: 3 Na+ out, 2 K+ in. Because 3 positive charges leave while only 2 enter, the pump is electrogenic and contributes directly to the resting membrane potential (more negative inside).
Other major ATP-driven pumps:
Ca2+ ATPase (SERCA): pumps Ca2+ from cytoplasm into the ER. Keeps cytoplasmic Ca2+ extremely low (~100 nM) so small releases produce dramatic signaling.
H+/K+ ATPase: pumps H+ into stomach lumen, producing gastric acid. Target of proton pump inhibitors.
V-type ATPase: pumps H+ into lysosomes and other acidic compartments.
Secondary Active Transport
The transporter does NOT use ATP directly. Instead, it uses the energy stored in an ion gradient (usually Na+, built by the Na+/K+ ATPase). The Na+ moves down its gradient through the transporter, and the energy drags another molecule UP its gradient as a passenger.
Two classes:
Symporter (cotransporter): Na+ and the co-transported molecule move in the SAME direction. Example: SGLT1 in intestinal cells absorbs glucose against its gradient by coupling to Na+ flowing down its gradient.
Antiporter (exchanger): Na+ and the co-transported molecule move in OPPOSITE directions. Example: Na+/Ca2+ exchanger in heart cells pumps Ca2+ out using the Na+ gradient.
How many Na+ and K+ does the Na+/K+ ATPase pump per ATP, and in which directions?
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3 Na+ are pumped OUT of the cell and 2 K+ are pumped INTO the cell per ATP hydrolyzed. Net loss of one positive charge from inside the cell per cycle makes the pump electrogenic, contributing to the negative resting membrane potential.
What is the difference between a symporter and an antiporter?
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A symporter moves two different molecules in the SAME direction (e.g., SGLT1 moves Na+ and glucose both into the cell). An antiporter moves two different molecules in OPPOSITE directions (e.g., Na+/Ca2+ exchanger moves Na+ in and Ca2+ out). Both are secondary active transporters harnessing an ion gradient.
How can blocking the Na+/K+ ATPase indirectly increase intracellular calcium?
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The Na+/K+ ATPase normally keeps intracellular Na+ low. The Na+/Ca2+ exchanger (antiporter) pumps Ca2+ out of the cell using the Na+ gradient - flowing Na+ in, Ca2+ out. If the pump is blocked (e.g., by digoxin), intracellular Na+ rises. The Na+ gradient weakens, so the Na+/Ca2+ exchanger cannot pump Ca2+ out as effectively. Cytoplasmic Ca2+ rises, increasing cardiac contractility.