Primary Pumps Flashcards
What do P-type ATPases pump?
Give examples
Cations
K+ Na+ Ca2+ H+ Mg+
What are P-type ATPases inhibited by?
Micromolar amounts of orthovanadate
How does orthovanadate affect P-type ATPases?
Inhibits them by working in the same way, preventing phosphorylation
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Where do you find Na+/K+ ATPase in animal cells?
In most plasma membranes of animal cells
How many isoforms does the Na+/K+ ATPase pump have?
3 isoforms
What are the general functions of Na+/K+ ATPase?
Maintaining high K+ and low Na+ in the cytosol
Maintains Na+ electrochemical potential via Na+ coupled transport
What happens if Na+ builds up inside a cell?
It is toxic to the cell
What is the stoichemetry of Na+/K+ ATPase pumps?
3 Na+ and 2 K+ per ATP hydrolysed
What is the general structure of a Na+/K+ ATPase?
2 alpha (112kDa) and 2 beta (34 kDa) subunits
Where do we find H+ ATPases?
All plasma membranes of plant and fungal cells
Stoichiometry of H+ ATPases?
1H+ for every ATP hydrolysed
Functions of H+ ATPase pumps:
Expel excess H+ produced during metabolism
Generate H+ electrochemical gradient used to drive H+ coupled transport
Maintain negative transmembrane voltage (> - 200 mV)
Regulate cytosolic pH
Acidification of extracellular medium (loosen cell walls to allow cell to expand using vacuoles)
What is the structure of a H+ ATPase pump?
1 alpha (112 kDa) subunit
What does SERCA stand for?
Sarcoplasmic endoreticulum Ca2+ ATPase
Where are SERCA found?
Sarcoplasmic reticulum network of tubules storing Ca2+ in the muscle cell cytoplasm
Stoichiometry of SERCA?
2Ca2+ per ATP hydrolysed
Function of SERCA?
Restore low cytosolic Ca2+ after muscle contraction
Structure of SERCA
1 alpha subunit (3 isoforms)
Inhibitor of SERCA?
Thapsigargin
What does PMCA stand for?
Plasma membrane Ca2+ ATPase
Where are PMCA found?
Fungal, plant and animal plasma membranes
Function of PMCA?
Maintain low cytosolic Ca2+ (high cytosolic Ca2+ is cytotoxic)
Central role in cell signalling
Structure of PMCA?
1 alpha subunit
Stoichiometry of PMCA?
Swaps 1 - 2 Ca2+ for a H+ per ATP
Where do you find H+/K+ ATPase?
Plasma membrane of gastric epithelium cells (stomach wall)
Function of H+/K+ ATPase
H+ secretion in to the lumen of the stomach to maintain acidic environment (=0.16 M HCl)
Structure of H+/K+ pump
2 alpha and 2 beta subunits
Stiochiometry of gastric muscosal H+/K+ ATPase?
2K+ for 2H+ per ATP
What is the function of CPx pumps?
Work similarly to P-type pumps, but target toxic transition metals that disrupt normal physiological functions
What kind of toxic transition metals do CPx pumps target?
Cu, Pb, Cd, Zn
(Copper, lead, cadmium, zinc)
What disease is associated with systemic copper deficiency?
Menkes disease (neurological disease, neurones don’t have enough copper)
What disease is associated with excessive copper accumulation in the liver?
Wilsons disease
If someone is suffering from Wilsons or Menkes disease, what do they likely have a problem with?
CPx pumps, which target transition metals such, as in this case, copper
What does the COPA pump do?
Pumps out excess copper (copper can be toxic to cells)
What does the COPB pump do?
Pumps in copper when the cell is deficient in it
Why is the pump named CPx ?
Amino acid motif of cysteine, proline and either cysteine, histidine or serine
Why are the cysteine repeats important in a CPx pump?
To stabilise the binding of the transition metal the pump is trying to transport
What is the purpose of region B in CPx pumps and P-type ATPases?
Induces conformational changes in ion binding site
What is the purpose of region C in CPx pumps and P-type ATPases?
Phosphorylation site and nucleotide binding site
What is the purpose of region J in CPx pumps and P-type ATPases?
Hinge to allow cytosolic regions to move and interact
Allows protein to flex to expose binding sites to ions, one side to the other
What is the main function of V-type pumps?
To generate the H+ electrochemical gradient required across intracellular membranes for associated carriers to fulfil their function
(eg; for an antiporter requiring H+ to transport a neurotransmitter across a vesicle membrane to store it in that vesicle)
Give an example for what might be powered by a V-type pump in animal cells
An antiporter requiring H+ to transport a neurotransmitter across a vesicle membrane to store it in that vesicle
What is the main purpose of the ABC transporters?
Use energy from ATP hydrolysis to transport a wide variety of solutes in or out of the cell, allowing it to acquire nutrients or get rid of toxins or drugs
What are MDR transporters?
“Multiple drug resistance” allow cell to pump toxins or drugs out of them, problematic in pathogenic or cancerous cells as it makes them resistant to these drugs/treatments (so some drugs target these transporters)
What causes cystic fibrosis?
An ABC transporter wrongly acts as an ATP-gated ion channel / transporter for chloride ions
