Podcast
Questions and Answers
What structural feature is common among all GPCR families?
What structural feature is common among all GPCR families?
Which family of receptors is NOT part of the GPCR superfamily?
Which family of receptors is NOT part of the GPCR superfamily?
What is one of the primary roles of receptor tyrosine kinases (RTKs)?
What is one of the primary roles of receptor tyrosine kinases (RTKs)?
What occurs when a ligand dissociates from its receptor?
What occurs when a ligand dissociates from its receptor?
Signup and view all the answers
What kind of signaling pathways are GPCRs involved in?
What kind of signaling pathways are GPCRs involved in?
Signup and view all the answers
Retosiban is known for its role as which type of drug?
Retosiban is known for its role as which type of drug?
Signup and view all the answers
Why do different tissues respond uniquely to signal molecules?
Why do different tissues respond uniquely to signal molecules?
Signup and view all the answers
What percentage of proteins coded in the human genome are estimated to be plasma membrane receptors?
What percentage of proteins coded in the human genome are estimated to be plasma membrane receptors?
Signup and view all the answers
What occurs when a charged substance is translocated without moving an opposite charge?
What occurs when a charged substance is translocated without moving an opposite charge?
Signup and view all the answers
Which transport mechanism involves moving two or more species in the same direction?
Which transport mechanism involves moving two or more species in the same direction?
Signup and view all the answers
What is the role of the electrochemical-potential gradient in transport mechanisms?
What is the role of the electrochemical-potential gradient in transport mechanisms?
Signup and view all the answers
Which of the following describes transporters that cannot create a concentration gradient across membranes?
Which of the following describes transporters that cannot create a concentration gradient across membranes?
Signup and view all the answers
When does a transport mechanism become classified as electrically silent?
When does a transport mechanism become classified as electrically silent?
Signup and view all the answers
Which transport mechanism involves the transport of a single solute?
Which transport mechanism involves the transport of a single solute?
Signup and view all the answers
What defines the antiport mechanism in transport?
What defines the antiport mechanism in transport?
Signup and view all the answers
What is common to all electrochemical-potential-driven transporters?
What is common to all electrochemical-potential-driven transporters?
Signup and view all the answers
What occurs when acetylcholine binds to the nicotinic-acetylcholine receptor?
What occurs when acetylcholine binds to the nicotinic-acetylcholine receptor?
Signup and view all the answers
Which ion's permeability is reduced in patients with Cystic Fibrosis (CF)?
Which ion's permeability is reduced in patients with Cystic Fibrosis (CF)?
Signup and view all the answers
What is the role of phosphorylation in the regulation of CFTR?
What is the role of phosphorylation in the regulation of CFTR?
Signup and view all the answers
What effect do antagonists have on ligand-regulated channels?
What effect do antagonists have on ligand-regulated channels?
Signup and view all the answers
Which type of channel allows for the rapid passage of ion flow, essential for nerve conduction?
Which type of channel allows for the rapid passage of ion flow, essential for nerve conduction?
Signup and view all the answers
What kind of agents are used to enhance the activity of ligand-gated channels?
What kind of agents are used to enhance the activity of ligand-gated channels?
Signup and view all the answers
How do neurotoxins affect the nicotinic-acetylcholine receptor?
How do neurotoxins affect the nicotinic-acetylcholine receptor?
Signup and view all the answers
What primarily confirms the diagnosis of Cystic Fibrosis in a patient?
What primarily confirms the diagnosis of Cystic Fibrosis in a patient?
Signup and view all the answers
Which condition is NOT associated with increased AQP2 levels leading to extracellular fluid volume expansion?
Which condition is NOT associated with increased AQP2 levels leading to extracellular fluid volume expansion?
Signup and view all the answers
How does nephrogenic diabetes insipidus primarily affect urine output?
How does nephrogenic diabetes insipidus primarily affect urine output?
Signup and view all the answers
What is the transport rate comparison between channels and specific transporters?
What is the transport rate comparison between channels and specific transporters?
Signup and view all the answers
What defines the movement mechanism of transporter proteins?
What defines the movement mechanism of transporter proteins?
Signup and view all the answers
What deficiency is indicated by individuals lacking AQPl activity?
What deficiency is indicated by individuals lacking AQPl activity?
Signup and view all the answers
Which statement best describes pores and channels in membrane transport?
Which statement best describes pores and channels in membrane transport?
Signup and view all the answers
What is a common characteristic of transport proteins based on their classification?
What is a common characteristic of transport proteins based on their classification?
Signup and view all the answers
Which of the following ions is NOT mentioned as an influence in the context of aquaporin function?
Which of the following ions is NOT mentioned as an influence in the context of aquaporin function?
Signup and view all the answers
What mechanism is primarily responsible for the transport of glucose across the plasma membranes of mammalian cells?
What mechanism is primarily responsible for the transport of glucose across the plasma membranes of mammalian cells?
Signup and view all the answers
Which type of ATPase is responsible for transporting Ca2+ back into the endoplasmic reticulum?
Which type of ATPase is responsible for transporting Ca2+ back into the endoplasmic reticulum?
Signup and view all the answers
What is the role of the Na+ independent Cl- - HCO3- exchanger?
What is the role of the Na+ independent Cl- - HCO3- exchanger?
Signup and view all the answers
In which condition is there a defect in the sodium-coupled glucose-galactose transporter?
In which condition is there a defect in the sodium-coupled glucose-galactose transporter?
Signup and view all the answers
What type of transport mechanism do glucose and amino acids utilize together with Na+?
What type of transport mechanism do glucose and amino acids utilize together with Na+?
Signup and view all the answers
What condition results from a decrease in the transport of neutral amino acids?
What condition results from a decrease in the transport of neutral amino acids?
Signup and view all the answers
Which of the following is specifically responsible for the abnormal renal reabsorption of cystine and basic amino acids?
Which of the following is specifically responsible for the abnormal renal reabsorption of cystine and basic amino acids?
Signup and view all the answers
In hypophosphatemic, vitamin D – resistant rickets, which type of absorption is abnormal?
In hypophosphatemic, vitamin D – resistant rickets, which type of absorption is abnormal?
Signup and view all the answers
Study Notes
GPCRs
- Form a superfamily of membrane proteins with five distinct families
- All share common structural motifs: seven transmembrane (TM) helices connected to three extracellular loops and three intracellular loops.
- Have unique combinations of signal-transduction activities involving G protein-dependent and G protein-independent signaling pathways.
Receptor Tyrosine Kinases (RTKs)
- A subclass of tyrosine kinases involved in cell-to-cell communication and controlling various biological functions such as cell growth, motility, differentiation, and metabolism.
- 58 known RTKs in humans, all share a similar protein structure with an extracellular ligand binding domain, a single transmembrane helix, and an intracellular region containing a juxtamembrane regulatory region, a tyrosine kinase domain (TKD), and a carboxyl (C-) terminal tail.
Receptor Binding
- Binding of a signal molecule to its receptor is an equilibrium process, similar to substrate binding in enzymes, but most cases involve no chemical modification of the bound ligand.
- Receptors are excellent targets for pharmaceuticals.
Oxytocin Receptor Antagonist
- Retosiban (GSK-221,149-A) is an oral drug that acts as an oxytocin receptor antagonist.
- Blocks oxytocin-mediated uterine smooth muscle contraction during preterm labor, preventing preterm labor and premature birth.
Membrane Transport Proteins
- A functional classification system by the International Union of Biochemistry and Molecular Biology (IUBMB) categorizes them into classes, subclasses, families, and subfamilies based on transport mechanism and properties.
- Many are present in prokaryotes and both prokaryotes and eukaryotes, including mammals.
- Structural homology exists among proteins in many subfamilies.
Pores and Channels
- Contain an aqueous pore through which molecules diffuse; movement is controlled by a gating mechanism.
Transporter Proteins
- Similar to enzymes, they bind the solute on one side of the membrane, change conformation, and move the substrate to the opposite side.
Characteristics of Pores/Channels and Transporters
- Most have a high degree of solute specificity.
- Substrate translocation rate is higher in channels (about 10 7 ions/ s) than in specific transporters (about 10 2 - 10 3 molecules/s).
Ligand-Regulated Channels
- Respond to binding of specific extracellular or intracellular chemical ligands (agonists), leading to channel opening or closing.
- For example, acetylcholine binding to the nicotinic-acetylcholine receptor opens the channel, allowing Na+ flow into the cell, crucial for neuronal electrical signal transmission.
- Neurotransmitters, cAMP, inositol l,4,5-trisphosphate, diacylglycerol, and G proteins can control other channels.
- Fast channel opening allows rapid bursts of ion flow (10 7 ions per second), essential for nerve conduction and muscle contraction.
Nerve Terminal Surface
- Contains various channels, including voltage-dependent channels for Ca2+, K+, Ca2+-gated K+ channels, ligand-gated channels, and stretch-activated channels.
Neurotoxins and Channel Inhibition
- Neurotoxins such as d-tubocurarine (curare's active ingredient) and snake toxins like a-bungarotoxin, erabutoxin, and cobratoxin inhibit the nicotinic-acetylcholine receptor.
- Succinylcholine, a muscle relaxant, opens the channel leading to membrane depolarization, used in surgeries due to its reversible activity after administration.
Channel Regulation
- Ligand binding and phosphorylation-dephosphorylation can control some channels.
- Pharmacological agents can modulate channels, inhibitors are antagonists.
Cystic Fibrosis (CF)
- CF patients have decreased Cl- permeability, impairing fluid and electrolyte secretion causing dehydration.
- Diagnosis is confirmed by significantly increased Cl- content in sweat.
- CF gene product is the cystic fibrosis transmembrane conductance regulator (CFTR ), a cAMP-dependent Cl- channel expressed in epithelial tissues and may regulate other ion channels.
- Phosphorylation by protein kinase A activates the channel.
Membrane Transport Protein Systems
- Some systems move two substrates in one direction and two substrates in opposite directions.
- Translocation of a charged substance without movement of an opposite charge or translocation of two molecules with different charges creates charge separation across the membrane, termed S’1 S’2 electrogenic transport, leading to membrane potential development.
- Movement of an oppositely charged ion to neutralize or moving two molecules of the same charge in opposite directions is termed neutral or electrically silent transport.
Electrochemical-potential Driven Transporters
- Uniport mechanism: transports a single solute by mediated diffusion or in a membrane-potential-dependent manner for charged solutes.
- Antiport mechanism: transports two or more solutes in opposite directions in a tightly coupled process without using energy other than the electrochemical-potential gradient. The gradient of one solute can drive the movement of the other.
- Symport mechanism: transports two or more species together in the same direction in a coupled process without using energy other than the electrochemical-potential gradient of one substrate.
Uniport Mechanism
- Involves transporting molecules down their chemical gradient (for uncharged molecules) or down an electrochemical gradient (for charged molecules). This is often referred to as protein-mediated diffusion or facilitated diffusion.
- These transporters cannot create a concentration gradient across the membrane.
Symport and Antiport Mechanisms
- Movement down a concentration gradient of one solute can drive the translocation of the other molecule.
- These are referred to as secondary active transporters, distinguished from primary active transporters.
Ca2+ Active Transport
- Two distinct Ca2+ -transporting ATPases (Ca2+ -ATPases) reestablish low cytosolic Ca2+ levels: one transporting Ca2+ back into the endoplasmic or sarcoplasmic reticulum lumen and the other out of the cell across the plasma membrane.
- Ca2+ -ATPases are P-type transporters, phosphorylated by ATP on an aspartyl residue.
Glucose Translocation
- Facilitated by a family of glucose transporters (GLUT ) through a uniport mechanism across mammalian cell plasma membranes.
Symport Mechanism for Glucose and Amino Acids
- Na+ driven transport of d-glucose, with two Na+ moving into the cell down their electrochemical gradient by passive facilitated transport and glucose carried along against its concentration gradient.
Antiport Mechanism for Cl- and HCO 3-
- An anion transporter in erythrocytes and kidneys mediates the electroneutral antiport movement of Cl- and HCO 3-.
- This transporter is referred to as the Na+ independent Cl-- HCO3 - exchanger or anion exchange protein.
- Important in adjusting erythrocyte HCO 3- concentration in arterial and venous blood.
- The kidney transporter is a truncated form of the erythrocyte protein responsible for base (HCO 3-) efflux to balance ATP-driven H+ efflux.
Diseases due to Loss of Membrane Transport Systems
- Individuals with decreased intestinal glucose uptake lack the specific sodium-coupled glucose-galactose transporter.
- Fructose malabsorption syndromes are caused by altered fructose transport system activity.
- Harnup disease involves decreased transport of neutral amino acids in intestinal and renal epithelial cells.
- Cystinuria has abnormal renal reabsorption of cystine and basic amino acids lysine, arginine, and ornithine, leading to renal cystine stones.
- Hypophosphatemic, vitamin D – resistant rickets involves abnormal renal phosphate absorption.
- Genetic diseases involving substrate transporters for dopamine and creatine, and the mitochondrial aspartate glutamate transporter have also been reported.
Studying That Suits You
Use AI to generate personalized quizzes and flashcards to suit your learning preferences.
Related Documents
Description
Explore the fascinating world of G protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs). This quiz covers their structures, functions, and signaling mechanisms in detail. Test your knowledge on these crucial components of cell communication.