Chapter 11.2 Transporters and Active Membrane Transport

Question 1

What are the three (3) types of active transport mechanisms?

two possible answers

Answer 1

I.
1. Coupled transporters
2. ATP-driven pumps
3. Light- or redox-driven pumps
II.
1. Primary active transport directly uses ATP.
2. Secondary active transport uses energy from another gradient.
3. Bulk transport moves large particles or molecules via vesicles.

Question 2

They use the energy from the downhill transport of one solute to drive the uphill transport of another solute.

Answer 2

Secondary Active Transport (Coupled transporters)

Question 3

In this transport/pump, ATP hydrolysis provides the energy needed to pump solutes uphill against their electrochemical gradient. Give an example of this pump.

Answer 3

ATP-driven pumps
ex.: Na+-K+ pump

Question 4

In membrane transport, it is the maximum rate at which a transporter can move solutes when all binding sites are occupied.

symbol

Answer 4

Vmax

Question 5

In membrane transport, it represents the solute concentration at which the transport rate is half of its maximum value, reflecting the affinity of the transporter for the solute.

Answer 5

Km (Michaelis constant)
- a key parameter in enzyme kinetics and transporter-mediated processes that reflects the affinity of an enzyme or transporter for its substrate (or solute, in the case of transporters)

Question 6

Molecules that compete with the solute for the same binding site on a transporter, potentially blocking transport.

Answer 6

Competitive inhibitors

Question 7

It is the intermediate state where the solute is not accessible from either side of the membrane during transport. This prevents solutes or ions from crossing the membrane unaccompanied and ensures tight coupling between ion and solute transport.

Answer 7

Occluded state in transporter

Question 8

Couple the uphill transport of solutes to energy input from light (e.g., bacteriorhodopsin, photosystem II) or from a redox reaction (e.g., cytochrome c oxidase).

Answer 8

light- or redox-driven pumps

Question 9

A transporter alternates between three states: (1), (2), and (3)_. These transitions are random, reversible, and occur regardless of solute binding, allowing solutes to move down their concentration or electrochemical gradient.

Answer 9

1) outward-open (binding sites exposed to the outside)
2) occluded (binding sites inaccessible)
3) inward-open (binding sites exposed to the inside).

Question 10

(1)__ reaches a maximum rate (Vmax) when the transporter is saturated, and the solute concentration at half Vmax is called Km. (2)__ and (3)__ increase linearly with solute concentration, but (1) is slower, moving solutes at rates of 10² to 10⁴ molecules per second, compared to (3) that can conduct up to 10⁸ molecules per second.

what kind/type of transport?

Answer 10

1) Transporter-mediated diffusion
2) Simple diffusion
3) channel-mediated transport

Question 11

What are the main types of coupled transporters, and how do they function?

Answer 11

• Coupled transporters either transfer solutes in the same direction (symporters) or in opposite directions (antiporters).
• They use the energy from one solute’s electrochemical gradient (often Na+) to drive the transport of another solute, allowing for active transport of solutes against their electrochemical gradients.

Question 12

In ___ (what kind of cell), Na+-driven symporters use the Na+ electrochemical gradient to import sugars or amino acids. __ transporters, also Na+-driven symporters, reabsorb neurotransmitters after their release at synapses, recycling them for reuse and terminating their signaling.

Answer 12

• epithelial cells
• Neurotransmitter

Question 13

a type of transporter that facilitates the passive movement of a single solute across the membrane, driven by the solute’s concentration gradient. The rate of transport is determined by the transporter’s Vmax and Km values.

Answer 13

uniporter

Question 14

Coupled transporters use the energy stored in the electrochemical gradient of one solute (usually Na+ in animal cells) to transport another solute against its electrochemical gradient, a process called __.

Answer 14

secondary active transport

Question 15

How do Na+-driven symporters work in intestinal and kidney epithelial cells?

Answer 15

Na+-driven symporters use the Na+ gradient to import sugars or amino acids into the cell. As Na+ moves down its electrochemical gradient, it “drags” the solute with it, facilitating the uptake of nutrients.

Question 16

(1)__ uses the energy stored in the electrochemical gradient of one solute to drive the active transport of another solute. In contrast, (2)__ directly uses energy from ATP hydrolysis to pump solutes against their electrochemical gradients.

Answer 16

1) Secondary active transport
2) primary active transport

Question 17

Neurotransmitter symporters function, and why are they important drug ta

• __ symporters reabsorb neurotransmitters (like dopamine, norepinephrine, and serotonin) into nerve cells after synaptic signaling.
• Drugs like __ (e.g., cocaine, amphetamines) and __ (Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) target these symporters to prolong neurotransmitter signaling by __ their reabsorption.
• __ - It results in heightened stimulation of the postsynaptic neuron and produces a sense of euphoria or increased energy
• __ - an increase in their concentration in the synapse, helps improve mood and alleviate the symptoms of depression.

Answer 17

• Neurotransmitter
• stimulants
• antidepressants
• inhibiting
• drugs
• Antidepressants

Question 18

Many transporters are built from bundles of 10 or more __ that span the membrane, with solute- and ion-binding sites located midway through the membrane. These sites are accessible via passageways that alternate between inward-open and outward-open conformations, enabling solute transport.

Answer 18

α helices

Question 19

refers to the structural similarity between the two halves of a transporter protein, with each half being an inverted repeat of the other. This symmetry allows the transporter to alternate access to binding sites for ions and solutes, facilitating their movement across the membrane.

Answer 19

Pseudosymmetry

Question 20

In which organisms do H+ gradients drive active transport (4), and why is this significant?

Answer 20

• bacteria, yeasts, plants, and membrane-enclosed organelles of animal cells.
• This reflects the predominance of H+ pumps in these membranes, allowing the inward transport of sugars and amino acids in organisms that do not rely on Na+ gradients.

Question 21

Transporters likely evolved by __ of smaller ancestor proteins, resulting in the pseudosymmetric structure seen in many modern transporters, with inverted repeats in their α helices.

Answer 21

gene duplication

Question 22

What is an example of a channel protein built from inverted repeats? (2)

Answer 22

1) Aquaporin, a water channel
2) Sec61 channel, which moves nascent polypeptides into the endoplasmic reticulum

Question 23

Mechanism of glucose transport driven by Na+ gradient:

What drives the transporter to switch between inward-open and outward-open conformations?

Answer 23

Stochastic (random) fluctuations caused by thermal energy drive the transporter to switch between inward-open and outward-open conformations.

Question 24

Mechanism of glucose transport driven by Na+ gradient:

When does the transition to the occluded state occur in the Na+/glucose transporter?

Answer 24

occurs only when both Na+ and glucose are bound

Question 25

Mechanism of glucose transport driven by Na+ gradient:

What happens if the transporter opens outwardly after binding both Na+ and glucose? Inwardly?

Answer 25

• Outwardly - nothing is achieved, and the process restarts. Na+ and glucose need to be released inwardly for successful transport.
• Inwardly - Na+ dissociates quickly in the low-Na+ environment of the cytosol, followed by glucose dissociation due to the cooperative binding effect.

Question 26

What is LeuT and how is it related to human transporters?

Answer 26

LeuT is a bacterial Na+/leucine symporter related to human neurotransmitter transporters, such as the serotonin transporter.

Question 27

Why is it important for cells to regulate cytosolic pH? Give two (2) proteins and their optimal pH.

Answer 27

• Most proteins function optimally at specific pH levels
  1) lysosomal enzymes - low pH (~5)
  2) cytosolic enzymes - near-neutral pH (~7.2).

Question 28

Cells typically have __ that help pump out excess H+ to maintain cytosolic pH. They use the energy stored in the Na+ gradient to either transport H+ out of the cell directly or to bring HCO3- into the cell to neutralize H+.

Answer 28

Na+-driven antiporters

Question 29

The __ couples the influx of Na+ to the efflux of H+, helping to reduce acidity in the cytosol.

Answer 29

Na+-H+ exchanger (Sodium–hydrogen exchanger/antiporter)

Question 30

It couples the influx of Na+ and HCO3- to the efflux of Cl- and H+, pumping out one H+ and neutralizing another for each Na+ that enters.

Answer 30

Na^+-driven Cl^–HCO3^- exchanger (sodium-driven chloride-bicarbonate exchanger (NDCBE))

sodium-bicarbonate cotransporter (NBC) in combination with the chloride-bicarbonate exchanger (anion exchanger, AE), commonly found in cells that regulate intracellular pH.

Question 31

Which exchanger is more effective than the Na+-H+ exchanger (Sodium–hydrogen exchanger/antiporter) or Na+-driven Cl–HCO3- exchanger (sodium-driven chloride/bicarbonate exchanger (NDCBE))? Why?

Answer 31

• Na+-driven Cl^–HCO3^- exchanger (sodium-driven chloride/bicarbonate exchanger (NDCBE))
• It is twice as effective because it neutralizes two H+ ions for each Na+ ion that enters the cell.

Question 32

What happens to the activity of the Na+-H+ and Na+-driven Cl–HCO3- exchangers when cytosolic pH falls?

Answer 32

Both exchangers sense the decrease in pH and increase their activity to help restore balance.

Question 33

It adjusts cytosolic pH in the reverse direction by moving HCO3- out of the cell when the cytosol becomes too alkaline.

Answer 33

Na+-independent Cl–HCO3- exchanger (Sodium-independent Chlorine/Bicarbonate exchanger)

Question 34

They control the pH of intracellular compartments by pumping H+ into organelles like lysosomes, endosomes, and secretory vesicles.

Answer 34

ATP-driven H+ pumps

Question 35

Why is the electrochemical H+ gradient advantageous for intracellular transport?

Answer 35

It can dissipate and regenerate quickly, allowing for rapid switching of transport reactions.

Question 36

Why does creating an electrochemical H+ gradient require the movement of fewer H+ ions compared to Na+?

Answer 36

The concentration of H+ is much smaller (0.1 pM at pH 7) than that of Na+ and K+ (approximately 100 mM), making it more efficient to create a similar energy gradient.

Question 37

It is the process by which glucose is transported across an intestinal epithelial cell from the intestinal lumen to the extracellular fluid and into the blood.

Answer 37

transcellular transport of glucose

Question 38

the pathway of substances across an epithelium by passing through the intercellular spaces in between epithelial cells

Answer 38

paracellular transport

Question 39

A transport that involves the transportation of solutes by a cell through a cell.

Answer 39

transcellular transport

Question 40

1) How is glucose transported into the cell from the intestinal lumen?
2) How does glucose exit the cell into the extracellular fluid?

Answer 40

1) Glucose is pumped into the cell through the apical membrane by an Na+-powered glucose symporter.
2) Glucose passes out of the cell through a glucose uniporter located in the basal and lateral membrane domains, moving down its concentration gradient.

Question 41

• They are often referred to as transport ATPases because they hydrolyze ATP to ADP and phosphate to pump ions or other solutes across a membrane.
• They can work in either direction depending on the electrochemical gradients of their solutes and the ATP/ADP ratio; they hydrolyze ATP when the ratio is high and can synthesize ATP when it is low.

Answer 41

ATP-driven pumps

Question 42

What are the three principal classes of ATP-driven pumps?

Answer 42

1) P-type pumps
2) ABC transporters (ATP-binding cassette transporters)
3) F-type (and V-type) pumps

Question 43

• A multipass transmembrane proteins that phosphorylate themselves during the pumping cycle and are responsible for maintaining gradients of Na+, K+, H+, and Ca2+ across cell membranes.
• They primarily transport ions (such as Na⁺, K⁺, Ca²⁺) across membranes by hydrolyzing ATP. The most well-known example is the Na⁺/K⁺ ATPase, which actively maintains ion gradients across the plasma membrane.

Answer 43

P-type pumps

Question 44

Differ structurally from P-type ATPases and primarily pump small organic molecules across cell membranes.

Answer 44

ABC transporters (ATP-binding cassette transporters)

Question 45

• Turbine-like protein machines that transfer H+ into organelles (like lysosomes and vacuoles) to acidify their interiors.
• pump protons (H⁺) into organelles to acidify them

Answer 45

V-type pumps

Question 46

• Structurally related to V-type pumps and typically work in reverse, using the H+ gradient to synthesize ATP from ADP and phosphate instead of hydrolyzing ATP.
• They are found in the plasma membrane of bacteria, the inner membrane of mitochondria, and the thylakoid membrane of chloroplasts.

Answer 46

ATP synthases

Question 47

Where are ATP synthases found? (3)

Answer 47

1) plasma membrane of bacteria
2) inner membrane of mitochondria
3) thylakoid membrane of chloroplasts

Question 48

How is the H+ gradient that drives ATP synthesis generated? (3)

Answer 48

1) Electron-transport steps of oxidative phosphorylation in aerobic bacteria and mitochondria.
2) Photosynthesis in chloroplasts.
3) Light-driven H+ pump (bacteriorhodopsin) in Halobacterium.

Question 49

1) What is the typical concentration of free Ca²⁺ in the cytosol of eukaryotic cells?
2) How does the concentration of free Ca²⁺ in the cytosol compare to that outside the cell?

Answer 49

1) Approximately 10⁻⁷ M.
2) Approximately 10⁻³ M. (outside is higher)

Question 50

The influx of __ into the cytosol stimulates muscle contraction.

what ion

Answer 50

Ca²⁺

Question 51

It pumps Ca²⁺ from the cytosol back into the sarcoplasmic reticulum (SR) to maintain a steep concentration gradient.

Answer 51

P-type Ca²⁺ ATPase in skeletal muscle cells

Question 52

It accounts for about 90% of the membrane protein of the SR, facilitating the reuptake of Ca²⁺ after muscle contraction.

Answer 52

• Ca²⁺ pump
• Sarcoplasmic Reticulum Ca²⁺-ATPase (SERCA), a P-type ATPase

Question 53

What structural features do P-type ATPases share?

Answer 53

contain 10 transmembrane α helices and three cytosolic domains.

Question 54

What happens when Ca²⁺ binds to the Ca²⁺ ATPase?

Answer 54

• Ca²⁺ binding triggers conformational changes, closing the passageway to the cytosol and activating a phosphotransfer reaction.
• the binding of Ca²⁺ to the SERCA pump initiates a sequence of ATP hydrolysis, conformational changes, and ion translocation, ultimately facilitating the reuptake of calcium into the SR and allowing muscle relaxation.

Question 55

What is the significance of the transient self-phosphorylation of the pump during its cycle?

Answer 55

It is an essential characteristic of all P-type pumps, allowing the transport cycle to continue.

Question 56

What replaces the two Ca²⁺ ions after they exit the pump into the SR lumen?

Answer 56

Two H⁺ ions and water molecules stabilize the empty Ca²⁺-binding sites.

Question 57

It actively pumps Na⁺ out of the cell and K⁺ into the cell against their electrochemical gradients.

Answer 57

Na⁺-K⁺ pump (Na⁺-K⁺ ATPase)

Question 58

What type of ATPase is the Na⁺-K⁺ pump classified as?

Answer 58

It belongs to the family of P-type ATPases.

Question 59

1) How many Na⁺ ions are pumped out of the cell for every ATP molecule hydrolyzed by the Na⁺-K⁺ pump?
2) How many K⁺ ions are pumped into the cell for every ATP molecule hydrolyzed by the Na⁺-K⁺ pump?

Answer 59

1) 3 Na+
2) 2 K+

Question 60

How much of an animal cell’s energy is typically devoted to fueling the Na⁺-K⁺ pump?

Answer 60

almost 1/3 of the cell’s energy

Question 61

In which types of cells does the Na⁺-K⁺ pump consume even more energy?

Answer 61

Nerve cells and cells dedicated to transport processes, such as those forming kidney tubules.

Question 62

What happens to aspartate during the pumping cycle of the Na⁺-K⁺ pump?

Answer 62

Aspartate is phosphorylated and dephosphorylated.
1) Aspartate undergoes phosphorylation during the binding of Na⁺, driving the conformational change that leads to Na⁺ release.
2) Dephosphorylation of aspartate occurs after K⁺ binding, triggering the return to the original state and K⁺ release into the cell.

Question 63

Na⁺-K⁺ pump drives three positively charged Na⁺ ions out of the cell for every two K⁺ ions pumped in, creating a net electric current. What do you call this process or mechanism?

Answer 63

electrogenic
definition: refers to a process or mechanism that generates an electrical charge imbalance across a biological membrane, leading to a net movement of positive or negative charges.

Question 64

How much (in percentage) of the membrane potential does the electrogenic effect of the Na⁺-K⁺ pump typically contribute? What accounts for the remaining __% of the membrane potential?

Answer 64

• more than 10% to the membrane potential
• remaining 90% of the membrane potential depends only indirectly on the Na⁺-K⁺ pump.

Question 65

What are F-type ATPases typically called and what is their primary function?

Answer 65

They are called ATP synthases and their primary function is to synthesize ATP from ADP and phosphate using the H⁺ gradient.

Question 66

• The largest family of membrane transport proteins and is especially important clinically.
• They undergo conformational changes driven by ATP binding and hydrolysis, alternating the exposure of solute-binding sites on either side of the membrane.

Answer 66

ABC transporters

Question 67

What does “ABC” in ABC transporters stand for?

Answer 67

ATP-binding cassettes, referring to the two conserved ATPase domains in each transporter.

Question 68

What was the first type of ABC transporter to be characterized?

Answer 68

ABC transporters in bacteria, which use the H⁺ gradient to import small molecules across the membrane.

Question 69

In gram-negative bacteria, like Escherichia coli, that have double membranes, the ABC transporters located in the __, and __ in the __ typically capture the nutrients and deliver them to the transporters.

Answer 69

• inner membrane
• auxiliary proteins
• periplasm

Question 70

(1)__ brings the ATPase domains together, and (2)__ drives conformational changes that alternate the exposure of solute-binding sites on either side of the membrane.

Answer 70

1) ATP binding (phosphorylation)
2) ATP hydrolysis

Question 71

Where are ABC transporters commonly found?

Answer 71

They are found in both bacteria (importing molecules) and eukaryotes (often exporting molecules like drugs).

Question 72

What role do ABC transporters play in drug resistance?

Answer 72

multidrug resistance (MDR) protein or (P-glycoprotein) transporter - pump hydrophobic drugs out of the cytosol, contributing to multidrug resistance in cancer cells.
- elevated levels in many human cancer cells and makes the cells simultaneously resistant to a variety of chemically unrelated cytotoxic drugs that are widely used in cancer chemotherapy.

Question 73

• An ABC transporter that pumps hydrophobic drugs out of the cytosol, contributing to multidrug resistance in cancer cells.
• elevated levels in many human cancer cells and makes the cells simultaneously resistant to a variety of chemically unrelated cytotoxic drugs that are widely used in cancer chemotherapy.

Answer 73

Multidrug resistance (MDR) protein or P-glycoprotein

Question 74

An ABC transporter in most vertebrate cells that pumps peptides from the cytosol into the ER lumen, where they are later presented on the cell surface to cytotoxic T lymphocytes for immune surveillance.

Answer 74

Transporter associated with antigen processing or TAP transporter

Question 75

What disease is associated with a malfunctioning ABC transporter, and which transporter is involved? Explain.

Answer 75

• Cystic fibrosis is caused by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) protein, an ABC transporter that regulates Cl⁻ transport in epithelial cells.
• This disease is caused by a mutation in the gene encoding CFTR, a Cl- transport protein in the plasma membrane of epithelial cells. CFTR regulates ion concentrations in the extracellular fluid, especially in the lung.

Question 76

An ABC transporter that regulates Cl⁻ transport in epithelial cells.

Answer 76

transmembrane conductance regulator (CFTR) protein

Question 77

How is CFTR different from most other ABC transporters?

Answer 77

Unlike other ABC transporters that use ATP hydrolysis to drive transport, CFTR uses ATP binding and hydrolysis to control the opening and closing of a passive Cl⁻ channel.

Question 78

What gene is amplified in Plasmodium falciparum that contributes to antimalarial drug resistance?

Answer 78

An ABC transporter gene that pumps out chloroquine, a drug used to treat malaria.