BB Lecture 15: Carrier Proteins Flashcards
What is primary active transport?
when a solute that is moved against its gradient has a binding site on a pump which directly carries it through the membrane
What is secondary active transport?
where a pump establishes a gradient for another solute (often Na+) across the membrane that can be harnessed by transporters to move a solute
What kinds of pumps have ATPase activity?
all pumps
List the different classes of pumps.
P-class V/F class ABC (ATP binding cassett) class
What are examples of P-class pumps?
Na+/K+ ATPase
SERCA
Describe the mechanism of a Na+/K+ ATPase pump.
three NA+ ions bind the high affinity sites in the cytoplasm (two low-affinity sites for K+ are unoccupied)
ATP binds the pump and is hydrolyzed by its ATPase activity
aspartate residue on the cytoplasmic side is phosphorylated
pump undergoes conformational change
Na+ ions move to low affinity sites exposed to the extracellular space and release
3 Na+ ions diffuse away
two K+ ions bind to the now high affinity sites on the intracellular side
hydrolysis of the aspartyl-phosphate bond
conformational change back to original state
release of K+ ions into extracellular space
What are P-class pumps?
move only ions across the membrane
all operate similarly to the Na+/K+ pump
What is a SERCA pump?
sarcoplasmic/endoplasmic reticulum Ca2+/ATPase
removes Ca2+ from the cytoplasm by sequestering it within intracellular storage organelles (the ER for most cells- SR in muscles)
Describe the mechanism of action for a SERCA pump.
just like a K+/Na+ pump but with Ca2+ and H+
What are V/F class pumps?
pump only protons V-class pumps contribute to acidification of organelles (eg. lysosome) by pumping protons from the cytoplasm to the lumen of the organelle F-class pumps use the movement of protons down their gradients to synthesize ATP
What are ABC class pumps?
ATP binding cassette pumps
transport uncharged and some hydrophobic molecules
diverse structurally and functionally
bind ATP through conserved regions (ATP binding cassettes)
undergo conformational change to the active site which hydrolyzes ATP to ADP
Provide examples of ABC-class pumps.
Multi-drug resistance (MDR) proteins
cystic fibrosis transmembrane regulator (CFTR)
What are MDR proteins?
ABC class pumps
expressed highly in epithelial cells
transport small, polar molecules (including some products of normal metabolism)
also can pump a wide variety of drugs out of cells
What are CFTR proteins?
ABC class pumps expressed in lungs and other organs DOES NOT HAVE a known pumping function incorporates a channel permeable to Cl- ions and is regulated by protein kinase A operates in cycles to open and close the Cl- channels
What are unitransporters?
conduct a single species of molecule down its gradient
use facilitated diffusion
What is facilitated diffusion?
a thermodynamically favored process that circumvents the hydrophobic barrier of the lipid bilayer and transport molecules
What is a co-transporter?
couple thermodynamically favorable movement of one type of molecule (down its gradient) to the unfavorable movement of another (secondary active transport)
What are the kinds of co-transporters?
symporter (move different solutes in the same direction across the membrane)
exchanger/antiporter (move the solutes in opposite directions)
What is a GLUT?
glucose uniporter
binds single molecule of glucose at a time
conformational change exposes the glucose-binding site alternately to the extracellular and intracellular sides
rate of cycle determined by occupation of binding site in a given conformation
direction of cycle determined by concentration gradient of glucose
What are SGLTs?
Na+/glucose transporters
couple Na+ influx to glucose uptake
Describe the use of SGLTs in the kidney.
SGLT-2 is expressed in the tubule near the glomerulus (glucose concentration high) and exchanges glucose at a 1xNa+ : 1xglucose ratio
SGLT-1 is expressed at the distal end (the glucose concentration is significantly lower –> glucose gradient not able to be used effectively) and exchanges 2xNa+ : 1xglucose to establish a greater gradient
essentially no glucose should be excreted into the urine
What is the Na+/Ca2+ exchanger (NCX)?
antiporter that couples Na+ entry to Ca2+ efflux (ratio of 3:1 respectively)
complementary to SERCA pump
contributes to Ca2+ clearance in cardiac cells
Which ion is most commonly used as a gradient for co-transporters?
Na+
because it has a resting membrane potential driving force that is much greater than ions like K+ and Ca2+ is highly regulated because of its use as an important second messenger
