Basolateral: rest of the cell's surface, interacts with blood/ECF
Trans- vs. Paracellular
Transcellular is through cells, paracellular is between them (via tight junctions).
How do the kidneys reabsorb nutrients?
Nutrients begin in lumen
Na+/K+ pumps create Na+ concentration gradient (Na+ goes out of cells)
Na+ gradient powers active transport of nutrients into cells via apical side
Nutrients exit cells via passive carrier proteins on basal side
Symptoms of CF
Thick mucus secretions and salty sweat.
Three hypotheses of how CF causes lung infections
1: A large decrease in Cl- absorption (mutant CFTR) --> increase in NaCl concentration on airway surfaces --> impedes natural antibiotics, leading to more infections
2: A large increase in Na+ absorption (no CFTR, no ENaC inhibition) --> water follows solute --> low airway surfaces liquid volume --> more infections
3: No CFTR-mediated HCO3- transport --> without HCO3- being secreted into the airways, pH gets too acidic (?) or causes a lack of defensins (?) --> more infections
Anion (Cl-) channel. Mutated in CF. Inhibits ENaC channel when working properly.
Exocrine vs. endocrine secretion
Exocrine: secretion into lumen
Endocrine: secretion into bloodstream (long-range)
Secretory gland for saliva
How does secretion work?
Cl- enters cell via basolateral side and exits via apical side (into lumen); water follows solute.
Cellular path of proteins that are destined for secretion
These proteins are made on the rough ER, sent to the Golgi, then the plasma membrane.
Pulse-Chase experiments (and results)
Add labeled amino acids to pancreatic cells for only three minutes to see where proteins that were synthesized during those three minutes go.
3 min: rough ER
10 min: Golgi
30 min: ready for secretion @ membrane
Pores that trap growing polypeptides halfway across the lipid bilayer. Periodically open during the protein's growth to give it a chance to stay in cytosol or head to the membrane.
Cover vesicles and help with curvature AKA formation of the vesicles.
SNARES (2 types)
Proteins that assist with vesicle fusion.
v-SNARES: In the Vesicle, bind to t-SNARES
t-SNARES: Extend from vesicle's Target location
Endocrine vs. paracrine agents
Endocrine agents, AKA hormones, transmit signals over long distances
Paracrine agents affect nearby cells
Dissociation equation (a smaller Kd means. . ?)
Smaller Kd means more sensitive signal reception.
Agonist vs. antagonist
Agonists are ligands that are activators
Antagonists are ligands that are inhibitors
Na+ (and some Ca++) channel that requires two Ach molecules to bind for it to open. Nicotine can do the function of Ach.
GPCR: cAMP Pathway
Ligand binds GPCR --> activates G-protein --> β and γ subunits head off to open a K+ channel and inhibit some Ca++ channels --> α subunit activates/inhibits adenylyl cyclase --> adenylyl cyclase increases/decreases cAMP levels --> 4 cAMP molecules activate PKA complex
GPCR: Ca++ Pathway
Ligand binds GPCR --> activates G-protein --> β and γ subunits head off to open a K+ channel and inhibit some Ca++ channels --> α subunit activates PLC --> PLC hydrolyzes (splits) PIP2 into IP3 and DAG --> IP3 releases Ca++ from the ER, DAG activates PKC
Protein that requires 4 Ca++ molecules to bind. Once activated, calmodulin can binds to and activate other proteins.
Methods of GPCR regulation (@ receptor, G-protein, and second messengers)
Receptor: desensitization, down regulation
G-protein: GTPase, lipid modification
Second messengers: elimination of second messengers from cell
Norepinephrine binds β-receptor --> G-protein, adenylyl cyclase, cAMP, PKA --> PKA phosphorylates SNARES, causing them to fuse and secrete their proteins
How does salivation work?
IP3 releases Ca++ from the ER. This Ca++ activates Cl- channels and transporters, allowing Cl- to leave the cell. Water follows solute - voila! Salivation!
What causes Cholera?
Constant activation of G-proteins (and thus adenylyl cyclase --> cAMP --> PKA), and PKA keeps CFTR activated.
Nuclear Receptor Superfamily
Large class of intracellular receptors that control hormones and nutrients as signals. Each has three sections: activation, DNA binding, and ligand binding.
A simple (just has an α subunit) G-protein that activates MAP kinase.
*Some cancers are caused by a mutated Ras that results in continual activation.
Regulates the entire cell cycle.
Receptor Tyrosine kinases
Once activated (ligands bind) they dimerize, and then activate Ras with the classic GDP --> GTP.