Membranes part 3

What are transporters/permeases?

Membrane proteins that provide an alternative diffusion path for polar molecules, lowering the activation barrier for transmembrane transport

Why do polar molecules have a high activation barrier for passive diffusion?

Passive diffusion of polar molecules requires desolvation (removal of water molecules), which requires a large input of energy

What types of molecules can passively diffuse through a membrane?

Small nonpolar molecules (no transporter needed)

What is simple diffusion?

Movement of nonpolar compounds down a concentration gradient without a protein transporter

What is facilitated diffusion?

Protein-assisted movement of a substance down its electrochemical gradient (no ATP required)

What is an ionophore?

A molecule that mediates ion transport down the electrochemical gradient by carrying ions through the membrane

What is an ion channel?

A protein pore that allows ions to move down their electrochemical gradient; may be gated by a ligand or voltage

What is primary active transport?

Transport of a substance against its electrochemical gradient, directly powered by ATP hydrolysis

What is secondary active transport?

Transport of a substance against its electrochemical gradient, driven by the favorable movement of a co-transported ion down its gradient (not directly by ATP)

How does a transporter lower the activation barrier for polar solute transport?

It provides a hydrophilic pathway through the membrane, eliminating the need for the solute to be desolvated while crossing the hydrophobic core

What is a uniport transporter?

A transporter that moves a single solute in one direction across the membrane

What is a symport transporter?

A cotransporter that moves two different solutes in the same direction simultaneously

What is an antiport transporter?

A cotransporter that moves two different solutes in opposite directions simultaneously

What is cotransport?

Transport involving movement of two solutes together; includes symport (same direction) and antiport (opposite directions)

Describe the 4-step model for GLUT glucose transport

1) Glucose binds stereospecific site on T1 conformation; 2) conformational change to T2 moves glucose across membrane; 3) glucose released into cytoplasm; 4) transporter resets to T1 conformation

What type of transporter is GLUT (e.g., GLUT2)?

A glucose uniporter that facilitates downhill (passive) efflux of glucose

How does glucose move from the intestinal lumen into an epithelial cell?

Via a Na⁺-glucose symporter on the apical surface, driven by the high extracellular [Na⁺]

How does glucose exit an epithelial cell into the blood?

Via GLUT2 (a glucose uniporter) on the basal surface, moving down the concentration gradient

What maintains the Na⁺ gradient that drives the Na⁺-glucose symporter?

The Na⁺/K⁺-ATPase on the basal surface, which pumps 3 Na⁺ out and 2 K⁺ in using ATP

What is the bicarbonate (chloride-bicarbonate) transporter?

An antiporter in red blood cells that exchanges HCO₃⁻ for Cl⁻, maintaining electrochemical balance across the membrane

How does CO₂ produced by tissues get transported in the blood?

CO₂ enters erythrocytes and is converted to HCO₃⁻ (+ H⁺) by carbonic anhydrase; HCO₃⁻ exits via the antiporter into plasma

How is CO₂ released at the lungs?

HCO₃⁻ re-enters the erythrocyte via the antiporter, is converted back to CO₂ by carbonic anhydrase, and CO₂ is exhaled

What is primary vs. secondary active transport?

Primary: directly uses ATP; Secondary: uses an ion gradient (itself maintained by primary active transport) to power uphill transport

What are ABC transporters?

ATP-Binding Cassette transporters; primary active transporters that use ATP hydrolysis (via nucleotide-binding domains) to pump substrates across the membrane

What do ABC transporters transport?

Amino acids, peptides, proteins, metal ions, lipids, and hydrophobic compounds across membranes

What are the two structural domains of ABC transporters?

Transmembrane domains (TMDs) — form the transport channel; Nucleotide-binding domains (NBDs) — hydrolyze ATP to power transport

What is the F-type ATPase?

A proton-driven ATPase that can use ATP hydrolysis to pump H⁺ across the membrane (acidifying a compartment) or use the proton gradient to synthesize ATP

What is ATP synthase (in context of F-type ATPases)?

An F-type ATPase in chloroplast and mitochondrial membranes that uses the proton gradient to synthesize ATP

What is the V-type ATPase?

A vacuolar ATPase that uses ATP to pump H⁺ into vacuoles or lysosomes, acidifying their lumen

How does F-type ATPase differ from V-type ATPase?

Both are proton pumps; F-type (in mitochondria/chloroplasts) can run in reverse to make ATP from a proton gradient; V-type (in vacuoles) only pumps protons using ATP

What are aquaporins?

Channel proteins that allow rapid, selective passage of water molecules across membranes

How do aquaporins allow water but exclude ions/protons?

Size restriction at the channel constriction, electrostatic repulsion from positively charged residues (His¹⁸⁰, Arg¹⁹⁵), and water dipole reorientation that breaks the proton-relay chain

What is the electrochemical gradient?

The combined gradient of concentration difference and electrical charge difference across a membrane that determines the direction of ion/solute movement

What is the K⁺ channel selectivity filter?

Backbone carbonyl oxygens that precisely cage K⁺, replacing its hydration shell — allowing rapid K⁺ passage while excluding Na⁺ (too small to be coordinated properly)

What is CFTR?

Cystic Fibrosis Transmembrane Conductance Regulator; a Cl⁻ ion channel in epithelial cells that opens when its R domain is phosphorylated AND ATP is bound to its NBDs

When is the CFTR channel open?

When the R domain is phosphorylated (by PKA) AND ATP is bound to both nucleotide-binding domains (NBDs)

When is CFTR closed?

When the R domain is unphosphorylated (regardless of ATP status), or when R domain is phosphorylated but no ATP is bound to NBDs

What disease results from a mutation in CFTR?

Cystic fibrosis — defective Cl⁻ channel leads to thick, dehydrated mucus in the lungs and other epithelia

What is the most common CFTR mutation in cystic fibrosis?

Deletion of Phe⁵⁰⁸ (ΔF508), which causes misfolding and premature degradation of the CFTR protein

Name a disease caused by a defect in a Na⁺ voltage-gated channel in skeletal muscle

Hyperkalemic periodic paralysis (gene: SCN4A)

Name a disease caused by a defect in a neuronal Na⁺ channel

Generalized epilepsy with febrile seizures (gene: SCN1A)

Name a disease caused by a defect in a cardiac Na⁺ channel

Long QT syndrome 3 (gene: SCN5A)

Name a disease caused by a defect in a neuronal Ca²⁺ channel

Familial hemiplegic migraine (gene: CACNA1A)

Name a disease caused by a defect in a K⁺ neuronal channel

Dominant deafness (gene: KCNQ4)

Name a disease caused by a defect in the Cl⁻ channel CFTR

Cystic fibrosis

Why do membrane lipid compositions vary across tissues/organelles?

To tune membrane fluidity, permeability, and protein function for the specific needs of each cell type or compartment

Summarize the key functions of membrane proteins

Structural support, active and passive transport of solutes, signal transduction, and cell-cell recognition