Membrane Transport and Body Fluid Compartments
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Questions and Answers

What are the two main types of gradients that play a role in the transport of solutes across membranes?

Electrical and concentration gradients.

Describe the primary difference between passive diffusion and active transport.

Passive diffusion occurs without energy input, while active transport requires energy to move solutes against their gradient.

What physiological example illustrates primary active transport?

The sodium-potassium pump (Na+/K+ ATPase) is a classic example of primary active transport.

What is the osmolality of intracellular water in a typical human adult?

<p>290 mOsm.</p> Signup and view all the answers

What role do aquaporins play in membrane transport?

<p>Aquaporins facilitate the passive diffusion of water molecules across the lipid bilayer.</p> Signup and view all the answers

How does secondary active transport differ from primary active transport?

<p>Secondary active transport utilizes the energy from primary active transport to move other substances against their gradient.</p> Signup and view all the answers

What is the main requirement for aqueous diffusion across the plasma membrane?

<p>It requires a concentration gradient.</p> Signup and view all the answers

How does facilitated diffusion differ from simple diffusion?

<p>Facilitated diffusion uses specialized carrier proteins for transport.</p> Signup and view all the answers

What is the role of energy in active transport?

<p>Active transport requires energy to move molecules against their concentration gradient.</p> Signup and view all the answers

Define endocytosis and explain how it occurs.

<p>Endocytosis is the invagination of the membrane to encase a molecule in a vesicle.</p> Signup and view all the answers

What happens to a solute during passive diffusion?

<p>A solute moves down its electrical and/or chemical gradient.</p> Signup and view all the answers

What does it mean for transport mechanisms to be non-coupled?

<p>Non-coupled transport means solute movement is independent of other solutes or chemical reactions.</p> Signup and view all the answers

What determines the permeability of the cell membrane to lipophilic solutes?

<p>The solute's lipophilicity determines its ability to cross the membrane.</p> Signup and view all the answers

How does a concentration gradient influence the transport mechanisms discussed?

<p>A concentration gradient drives the movement of solutes during passive and facilitated diffusion.</p> Signup and view all the answers

What is the primary mechanism by which drugs such as Ganaxolone diffuse across membranes?

<p>Simple passive diffusion due to its high lipid solubility.</p> Signup and view all the answers

How does the pKa of a drug affect its ionization and permeability through a membrane?

<p>The pKa determines the proportion of ionised versus un-ionised forms, influencing the drug's ability to permeate the membrane.</p> Signup and view all the answers

What happens to aspirin (pKa = 3.5) when it passes from the stomach to the plasma?

<p>It diffuses as a high percentage of un-ionised in the stomach but becomes mostly ionised in the plasma.</p> Signup and view all the answers

Why are weak acids and weak bases significant in the context of drug ionization?

<p>They exist in both ionised and un-ionised forms, affecting their absorption and distribution.</p> Signup and view all the answers

What is the effect of pH on drug ionization and how does it relate to pharmacology?

<p>pH influences the ionisation state, thereby affecting drug permeability and absorption in different compartments.</p> Signup and view all the answers

In what way does the blood-brain barrier impact drug transport?

<p>It restricts the passage of many drugs, requiring specific characteristics for effective transport.</p> Signup and view all the answers

What role do intestinal solute carrier proteins play in pharmacology?

<p>They facilitate the active transport and diffusion of nutrients and drugs across intestinal membranes.</p> Signup and view all the answers

Describe the concept of 'pH trapping' and its significance for drug absorption.

<p>It refers to the phenomenon where drugs become trapped in different compartments due to changes in their ionisation based on pH.</p> Signup and view all the answers

What is the role of ATP hydrolysis in primary active transport?

<p>ATP hydrolysis provides the energy necessary to move a solute against its electrochemical gradient.</p> Signup and view all the answers

Describe the initial affinity characteristics of the transporter in primary active transport.

<p>Initially, the transporter has a high affinity for Na+ and a low affinity for K+.</p> Signup and view all the answers

What is the significance of phosphorylation of the enzyme in the transport cycle?

<p>Phosphorylation transforms the enzyme, altering its affinity for sodium and potassium ions, which is crucial for the transport cycle.</p> Signup and view all the answers

Explain how secondary active transport depends on the Na+ gradient.

<p>Secondary active transport utilizes the energy from the Na+ gradient to facilitate the movement of sugars and amino acids against their gradients.</p> Signup and view all the answers

What happens during the transformation of the phosphoenzyme in the transport mechanism?

<p>The phosphoenzyme undergoes a transition that reduces its affinity for ADP and alters its affinities for Na+ and K+.</p> Signup and view all the answers

What does ouabain sensitivity indicate about the phosphoenzyme hydrolysis?

<p>Ouabain sensitivity suggests that hydrolysis of the aspartyl-phosphate bond is critical for enzyme activity and ion transport.</p> Signup and view all the answers

Identify the final step of the transport cycle.

<p>The final step is the return of the pump to its native enzyme form, completing the transport cycle.</p> Signup and view all the answers

How many modes can the Na+/K+ pump operate in, and why is this significant?

<p>The Na+/K+ pump can operate in at least five modes due to the reversibility of several steps in the reaction cycle.</p> Signup and view all the answers

What transport method is responsible for the absorption of glucose and galactose in the gut?

<p>Secondary active transport mediated by SGLT1.</p> Signup and view all the answers

How is fructose absorbed in the gut?

<p>Fructose is absorbed by facilitated diffusion mediated by GLUT5.</p> Signup and view all the answers

What is the role of GLUT2 in the absorption of monosaccharides?

<p>GLUT2 mediates the exit of all monosaccharides from the intestinal cells into the bloodstream via facilitated diffusion.</p> Signup and view all the answers

What characteristic must a substrate have to be transported via SGLT1?

<p>A substrate must be a hexose in the D-conformation or one that can form a pyranose ring.</p> Signup and view all the answers

What type of transport utilizes energy and can move molecules against a concentration gradient?

<p>Primary active transport.</p> Signup and view all the answers

Describe the function of the Na+/K+ ATPase pump.

<p>The Na+/K+ ATPase pump maintains the electrochemical gradients of Na+ and K+ across the membrane.</p> Signup and view all the answers

What molecules can enter cells through specialized carrier proteins?

<p>Hydrophilic, polar molecules can enter through specialized carrier proteins.</p> Signup and view all the answers

Identify the importance of primary active transport in relation to secondary active transport.

<p>Primary active transport, like the Na+/K+ ATPase, establishes concentration gradients necessary for secondary active transport.</p> Signup and view all the answers

What role does P-glycoprotein play in drug transport?

<p>P-glycoprotein acts as a multidrug transmembrane transporter responsible for drug resistance by actively transporting drugs out of cells.</p> Signup and view all the answers

How does the liver utilize P-glycoprotein for drug elimination?

<p>The liver uses P-glycoprotein to transport drugs into bile, facilitating their elimination from the body.</p> Signup and view all the answers

Describe the mechanism by which the kidneys excrete drugs.

<p>The kidneys utilize P-glycoprotein to pump drugs into the urine for excretion.</p> Signup and view all the answers

What mechanism governs Na+/glucose absorption in the jejunum?

<p>Na+/glucose absorption is primarily facilitated through secondary active transport mechanisms known as cotransport.</p> Signup and view all the answers

What is the significance of the negative transepithelial potential generated by Na+/K+ ATPase?

<p>The negative transepithelial potential drives the parallel absorption of chloride ions in the intestines.</p> Signup and view all the answers

How does the Na+/H+ exchange mechanism function in the jejunum?

<p>Na+/H+ exchange in the jejunum occurs at the apical and basolateral membranes, contributing to Na+ movement and intracellular pH regulation.</p> Signup and view all the answers

What is the role of NHE1 in Na+/H+ exchange?

<p>NHE1 acts as a 'cellular pH housekeeper' and regulates intracellular pH but does not contribute to transepithelial Na+ movement.</p> Signup and view all the answers

Explain the function of P-glycoprotein in the placenta.

<p>In the placenta, P-glycoprotein transports drugs back into maternal blood, reducing fetal exposure to potentially harmful substances.</p> Signup and view all the answers

Flashcards

Membrane Transport

The movement of substances across cell membranes.

Passive Diffusion

Movement of molecules across a membrane from high to low concentration without energy.

Concentration Gradient

Difference in concentration of a substance across a membrane.

Aquaporins

Water channels that facilitate water movement across membranes.

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Extracellular Fluid

Fluid outside cells, including interstitial and plasma water.

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Intracellular Fluid

Fluid inside cells.

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Primary Active Transport

Transport that moves molecules against their gradient and requires direct energy expenditure.

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Secondary Active Transport

Transport that uses the energy stored in an ion gradient to move another molecule against its gradient.

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Lipid-soluble molecule transport

Lipid-soluble molecules cross cell membranes directly, without needing help.

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Aqueous diffusion

Movement of a substance through a channel in the cell membrane (no energy needed).

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Facilitated diffusion

Use of carrier proteins to move substances across the cell membrane (no energy needed).

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Active transport

Movement of substances against their concentration gradient (requires energy).

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Endocytosis (Pinocytosis)

Cell membrane invaginates to engulf a substance, creating a vesicle.

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Passive transport

Movement of substances down their concentration gradient (no energy needed).

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Membrane permeability

Ability of the cell membrane to allow substances to pass through.

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Facilitated diffusion of glucose and fructose

Glucose and fructose enter cells through transport proteins (GLUTs) down their concentration gradient, requiring no energy.

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Secondary active transport of glucose/galactose

Glucose and galactose are absorbed using a transport protein (SGLT1) that uses the energy from sodium ions moving down their concentration gradient.

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GLUT2

A transporter protein that facilitates the exit of monosaccharides from the gut lining to the bloodstream.

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GLUT5

Facilitates fructose absorption in the gut.

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SGLT1

A transport protein that absorbs glucose and galactose using the energy from sodium ions.

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Na+/K+ ATPase pump

A primary active transport pump that moves sodium out and potassium into the cell, establishing concentration gradients.

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Drug Lipid Solubility (logP)

Measures how readily a drug dissolves in lipids (fats). High logP means the drug dissolves easily in lipids.

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pH and drug ionization

The pH of the environment affects how much of a drug is in its charged (ionized) form. This influences drug absorption.

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pKa

The pH value at which half of a drug molecule exists in its ionized form and half in its non-ionized form.

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pH trapping

A drug's ability to be trapped in an area with a different pH than its region of origin because of ionization differences.

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Blood-Brain Barrier

Specialized membranes that control the passage of substances into the brain, protecting it from harmful substances.

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Carrier-mediated transport

The movement of drugs across membranes via specific protein transporters. This can be facilitated or active.

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Intestinal solute carriers

Proteins that transport substances in and out of intestinal cells.

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Sodium-Potassium Pump

A protein that pumps sodium ions out of the cell and potassium ions into the cell, maintaining the cell's electrochemical gradient.

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Electrochemical Gradient

The combined effect of concentration gradient (difference in concentration) and electrical gradient (difference in charge) across a membrane.

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What is the role of ATP in the Sodium-Potassium Pump?

ATP provides the energy for the pump to move sodium ions out of the cell and potassium ions into the cell, against their concentration gradients.

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What is the role of the Sodium-Potassium Pump in maintaining cell volume?

The pump helps maintain cell volume by regulating the concentration of ions, which influences water movement.

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What is the significance of the Sodium-Potassium Pump in nerve impulse transmission?

The pump creates a concentration gradient that is essential for generating and conducting nerve impulses.

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What are the different modes of operation for the Sodium-Potassium Pump?

The pump can operate in at least five modes, depending on the concentration of sodium, potassium, ATP, and other factors.

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P-glycoprotein

A transmembrane protein that pumps drugs out of cells, contributing to multidrug resistance.

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Multidrug Resistance (MDR)

A phenomenon where cancer cells become resistant to multiple chemotherapy drugs due to overexpression of efflux pumps like P-glycoprotein.

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P-glycoprotein in Liver

Pumps drugs into bile for elimination from the body.

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P-glycoprotein in Kidneys

Pumps drugs into urine for excretion.

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P-glycoprotein in Placenta

Transports drugs back into maternal blood, protecting the fetus.

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P-glycoprotein in Intestines

Pumps drugs into the intestinal lumen, reducing absorption into the blood.

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P-glycoprotein in Brain Capillaries

Pumps drugs back into the blood, limiting drug distribution in the brain.

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Na+/K+ Pump (Primary Active Transport)

A membrane protein that uses ATP to pump sodium ions out of the cell and potassium ions into the cell, creating ion gradients.

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Study Notes

Membrane Transport

  • Membrane transport encompasses the movement of substances across cell membranes.
  • Learning outcomes include understanding normal membrane function regulation and physiological principles.
  • Students should grasp the roles of electrical and concentration gradients in solute transport across membranes.
  • Knowledge of passive diffusion, aqueous diffusion, facilitated diffusion, and active transport (including primary and secondary active transport) is crucial.
  • Students should be able to demonstrate physiological examples of these transport mechanisms.

Body Fluid Compartments

  • A 70kg adult has a total body water of approximately 42 Liters.
  • Extracellular fluid comprises plasma water (3L) and interstitial water (13L).
  • Intracellular fluid accounts for roughly 25L of total body water.
  • Key electrolyte concentrations differ significantly between these compartments.

Mechanisms of Membrane Transport

  • Passive diffusion: Small, lipid-soluble molecules move directly through the lipid bilayer or via aqueous pores (aquaporins) down their concentration gradient.
  • Aqueous diffusion: Molecules move down a concentration gradient through channels that span the membrane.
  • Facilitated diffusion: Specific carrier proteins assist movement of molecules down a concentration gradient without requiring energy.
  • Active transport: Carrier proteins transport molecules against their concentration gradient, requiring energy (e.g., ATP hydrolysis). This allows movement uphill.

Electrochemical Potential

  • Electrochemical potential is the sum of chemical and electrical potential energy differences.
  • Critical in understanding the driving forces for passive diffusion and aqueous diffusion.
  • At equilibrium, potential differences are equal but opposite.
  • The Nernst equation helps calculate the equilibrium potential for an ion.

Fick's Law

  • Fick's Law describes the flux of electrically neutral solutes across membranes.
  • The flux depends on the permeability coefficient of the solute, which relates to lipid-water partition coefficient, diffusion coefficient, and membrane thickness.
  • Higher lipid-water partition coefficients indicate easier transport across the membrane.

Lipid-Water Partition Coefficient (logP)

  • logP measures the relative solubility of a molecule in lipid versus water.
  • Hydrophobic molecules (logP >1) are more soluble in lipids and thus cross membranes easily.
  • Hydrophilic molecules (logP <1) are less soluble in lipids and thus cross membranes less easily.

Simple Passive Diffusion

  • The direction of movement is always down the concentration gradient from high to low concentration.
  • Drug molecules with higher logP values (more lipid soluble) diffuse across membranes more easily.
  • The transmembrane concentration gradient dictates the direction of simple passive diffusion.

Application to Pharmacology: pH and Ionization

  • Most drugs are weak acids or bases and exist in ionized and unionized forms.
  • Ionization depends on the drug's pKa and the local pH.
  • The non-ionized form of a drug typically crosses membranes more readily.
  • pH trapping can affect drug absorption and distribution.

Application to Pharmacology: P-glycoprotein

  • P-glycoprotein is a transmembrane transporter that pumps various substances out of cells.
  • It's vital in excreting drugs and contributes to resistance to multiple drugs.
  • P-glycoprotein impacts drug absorption, distribution, and elimination in organs like the liver, kidneys, intestines, and blood-brain barrier.

Primary and Secondary Active Transport

  • Primary active transport uses ATP to directly drive the movement of a molecule against its concentration gradient. Critical example is the Na+/K+ ATPase pump.
  • Secondary active transport couples the movement of one substance against its gradient to the movement of another down its gradient. Uses electrochemical gradients created by primary active transport.

Role of Na+ in Absorption

  • Na+-based mechanisms (e.g. Na+/glucose, and Na+/amino acid cotransport) are primary drivers of postprandial nutrient absorption.

  • Na+-H+ exchange is also important.

  • These processes are critically involved in maintaining homeostasis.

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BS31013 Lecture 1 2024-25 Membranes Transport PDF

Description

This quiz covers the concepts of membrane transport, including mechanisms such as passive diffusion and active transport. It also explores the composition of body fluid compartments and the role of electrolytes. Students will demonstrate their understanding of physiological principles related to these topics.

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