Chapter 4: Membranes and Transport

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What is diffusion?

Net movement of species across the biomembrane from high to low concentration.


What is simple diffusion?

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Movement of small, neutral molecules (e.g. O2, urea) through membranes without the aid of proteins.


What determines the rate of transport of small molecules by simple diffusion?

Their partition coefficient between oil and water; hydrophobicity is required for simple diffusion.


What is nephrogenic diabetes insipidus?

A disease characterized by mutation in a water-channel protein gene (aquaporin-2), which causes diuresis without hyperglycemia.


What are transporters?

Membrane proteins involved in the transport of larger, polar molecules, such as amino acids or sugars.


What are the two mechanisms of transporters?

  1. facilitated diffusion
  2. active transport

What is facilitated diffusion?

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When a transporter catalyzes movement of a substrate through a membrane down its concentration gradient and does not require energy.


What is active transport?

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When a transporter catalyzes movement of a substrate through a membrane up its concentration gradient; must be coupled with an energy-producing reaction.


What are ionophores?

Molecules that increase the permeability of membranes to specific ions.


How are ionophores used clinically?

As antibiotics that disturb of the ion-transport systems of bacterial membranes.


What are the two types of ionophores?

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  1. mobile ion carriers (e.g. valinomycin)
  2. channel formers (e.g. amphotericin)

Which is faster, facilitated diffusion or simple diffusion, and why?

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The rate of facilitated diffusion greater because it is catalyzed by transport proteins.


How are transporters similar to enzymes?

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They are saturable, having a maximum transport rate (Tmax), and specific; each can only transport a single species of molecule or structurally related compounds.


What is infantile cystinosis?

A disease caused by a defect in the lysosomal transport protein, cystinosine, resulting in accumulation of cystine in lysosomes and formation of crystalline precipitates in cells throughout the body.


What are GLUT transporters?

A family of glucose transporters that catalyze downhill transport of glucose into and out of cells.


What does GLUT-1 transport and where it is found?

It transports glucose, galactose, and mannose; it is found in erythrocytes and blood–tissue barriers.


What does GLUT-2 transport and where it is found?

It transports glucose and fructose; it is found in the liver, intestine, kidney, pancreas, and brain.


What does GLUT-3 transport and where it is found?

It transports glucose only; it is found everywhere throughout the body.


What does GLUT-4 transport and where it is found?

It transports glucose only; it is found in muscle and adipose tissue.


Where is GLUT-5 found?

It transports fructose only; it is found in the intestine.


What are membrane channels or pores?

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Open, less selective conduits for transport of ions, metabolites, and proteins across biomembranes.


What is voltage or ligand “gating”?

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Transmembrane voltage changes and ligand binding may induce conformational changes in channels that have the effect of opening or closing them.


What are gap junctions?

Clusters of pores between cell membranes joined by connexin that allow cell to cell interchange for physiologic communication or coupling (e.g. concerted contraction of uterine muscle during labor).


What is adenosine triphosphate (ATP)?

A high-energy product of metabolism and is often described as the “energy currency” of the cell.


How is ATP used for energy?

Its phosphoanhydride bond releases free energy when it is hydrolyzed to produce adenosine diphosphate (ADP) and inorganic phosphate.


What is primary active transport?

A transport system that uses ATP directly to drive transport of molecules up concentration gradients.


What is secondary active transport?

A transport system that uses an electrochemical gradient of Na+ or H+ ions or a membrane potential produced by primary active transport processes.


What are the four types of ATPases?

  1. F-ATPase (coupling factor)
  2. V-ATPase (vacuolar)
  3. P-ATPase (phosphorylation)
  4. ABC (ATP-binding cassette)

Where are F-ATPases found and what is their function?

It is found in mitochondrial, chloroplast, and bacterial membranes; it hydrolyzes ATP to transport H+.


What is unique about mitochondrial F-ATPase?

It works in the backward direction, synthesizing ATP from ADP and phosphate as protons move down the electrochemical gradient.


What is ATP–ADP translocase?

A transporter located in the inner mitochondrial membrane that transports newly synthesized ATP into the cytoplasm by antiport with ADP.


Where are V-ATPases found and what is their function?

It is found in cytoplasmic vesicles, such as lysosomes or secretory granules; it hydrolyzes ATP to transport H+ into these vesicles, acidifying their contents.


Where are P-ATPases found and what is their function?

They are found throughout the body; they form phosphorylated intermediates that drive ion translocation (e.g. Na+/K+-ATPase, Ca2+-ATPase).


What is Menkes disease?

An X-linked disease caused by a defect in a copper-transporting P-ATPase that results in an inability to transport copper out of intestinal cells, leading to copper deficiency and characteristic hypopigmented hair, cerebral degeneration, and death by age 3.


What is Wilson's disease?

A disease caused by a gene mutation encoding a copper-transporting P-ATPase failure to incorporate copper into ceruloplasmin in the live, leading to toxic accumulation of copper in the liver, kidney, brain, and cornea and characteristic neurologic damage.


Where are ABC transporters found and what is their function?

They are found in cellular, endoplasmic reticular, and peroxisomal membranes; they have roles in resistance to toxic metabolites (e.g. MRP) and in immune responses (e.g. TAP).


What is MRP?

It is multidrug resistance–associated protein, an ABC transporter associated with excretion of toxic metabolites and xenobiotics from cells, contributing to the resistance of cancer cells to chemotherapy.


What is TAP?

They are transporters associated with antigen presentation, a class of ABC transporters required for initiation of the immune response.


What is cystic fibrosis (CF)?

The most common autosomal recessive disease of Caucasian populations, caused by mutations in the CFTR gene that result in defects in a Cl channel, which leads to pancreatic insufficiency, an increased Cl in sweat, male infertility, and airway disease.


What are the three types of transport processes?

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  1. uniport
  2. symport
  3. antiport

What is an electrochemical gradient?

The combination of the concentration gradient (chemical potential) and the voltage gradient (electrical potential) across the membrane.


What is Na+/K+-ATPase?

It is an electrogenic transporter in the cell membrane that pumps out three Na+ ions for every two K+ ions pumped in, generating an inside-negative membrane potential.


What are voltage-dependent Ca2+ channels (VDCC)?

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They are channels in the T tubules of skeletal muscle that respond to membrane depolarization, activating release of Ca2+ through a channel in the sarcoplasmic reticulum membrane to initiating muscle contraction (depolarization-induced Ca2+ release).


What is Ca2+-ATPase?

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It is a transporter in the sarcoplasmic reticulum of skeletal muscle that hydrolyzes ATP to transport Ca2+ from the cytoplasm into the lumen of the sarcoplasmic reticulum, decreasing cytoplasmic Ca2+ and allowing the muscle to relax.


How do VDCCs in cardiac muscle differ from those in skeletal muscle?

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In cardiac muscle, VDCCs permit the entry of a small amount of Ca2+, which then stimulates Ca2+ release through the Ca2+ channel from the lumen of the sarcoplasmic reticulum (Ca2+-induced Ca2+ release).


What is SGLT1?

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An Na+-coupled glucose symporter that transports glucose uphill into the intestinal epithelial cell.


What is SGLT2?

An Na+-coupled glucose symporter that transports glucose uphill into renal proximal tubular epithelial cells.


What is KATP?

An ATP-sensitive K+ channel in pancreatic islet β-cells that closes in response to ATP produced by glucose metabolism, causing depolarization that activates VDCCs, which allow entry of Ca+ that stimulates exocytosis of vesicles that contain insulin.


What is persistent hyperinsulinemic hypoglycemia of infancy (PHHI)?

A disease caused by a defect in KATP that results an inability to transport K+, inducing low blood glucose concentration.


How do phenylalkylamine, benzothiazepine, and dihydropyridine work?

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They are Ca2+-channel blockers used to treat hypertension by inhibiting VDCCs, thus limiting the increase in cytoplasmic Ca2+ concentration required for forceful muscle contraction.


How do ouabain and digoxin work?

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They are Na+/K+-ATPase inhibitors used to treat congestive heart failure by lowering the Na+ concentration gradient used to drive export of Ca2+, thus keeping cytoplasmic Ca2+ concentration high.


How does lidocaine work?

It is a Na+-channel blocker used as a local anesthetic and antiarrhythmic drug by repressing transmission of the depolarization signal.


What is H+/K+-ATPase?

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A proton pump P-ATPase in gastric parietal cells that antiports two H+ ions protons and two extracellular K+ ions, to acidify the lumen of the stomach.


How does omeprazole work?

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It is a proton pump inhibitor that is activated in the acidic conditions of the gastric lumen (prodrug), used to treat gastric ulcers by inhibiting H+ transport into the gastric lumen.


How do cimetidine and ranitidine work?

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They are H2-blockers that indirectly inhibit acid secretion in the gastric lumen by competing with histamine for its receptor on gastric parietal cells.