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#proton pump

3 public questions tagged with this topic.

Membrane Transportation

Which of the following describes V-class ATPases?

V-class ATPases, vacuolar type H+-ATPases, are multi-protein rotary pumps distinct from glucose carriers SGLT or drug exporters ABCB1. They hydrolyze ATP in cytosolic V1 sector comprising A3B3 catalytic hexamer and use released energy to rotate central stalk and translocate protons through membrane-embedded Vo sector containing c-ring proteolipids and subunit a. Cellular localization includes lysosomes, endosomes, trans-Golgi network, synaptic vesicles, secretory granules, osteoclast ruffled border and kidney intercalated cell apical membrane. By acidifying compartments to pH 4.5-5.5 they create environment for acid hydrolase activation, protein processing, neurotransmitter loading via proton-coupled secondary transporters, and iron release from transferrin. In osteoclasts and kidney they pump H+ outward contributing to bone resorption and urine acidification. They do not transport glucose, which uses SGLT and GLUT families, nor export lipophilic drugs, which uses ABC transporters, and they are not restricted to bacteria but broadly expressed in eukaryotes for organellar pH regulation vital for autophagy and infection defense.

Ref: Forgac, Nat Rev Mol Cell Biol 2007, V-ATPase function; Nelson & Harvey, Annu Rev Cell Biol 1999.

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Membrane Transportation

Which pump is responsible for maintaining low pH in lysosomes?

Lysosomes function as degradative centers requiring low internal pH between 4.5 and 5 to activate more than fifty acid hydrolases such as cathepsins, sulfatases and lipases, while protecting cytosol from unwanted proteolysis. Acidic environment established primarily by vacuolar proton ATPase V-ATPase, large 900 kilodalton complex composed of peripheral V1 octamer A3B3CDE3FG3H hydrolyzing ATP at A-B interfaces and integral Vo domain a, c, c'', d, e, forming proton pore. Mechanism rotary: ATP hydrolysis in V1 drives rotation of central stalk D F and c-ring proteolipid assembling ten copies each with essential glutamate protonating deprotonating at half channels in subunit a, transporting protons from cytosol to lumen consuming roughly four protons per ATP. No phosphoenzyme intermediate forms. Specific inhibitors bafilomycin and concanamycin bind Vo. Na+/K+ ATPase maintains plasma gradients, F-type ATP synthase in mitochondria normally synthesizes ATP using proton gradient, ABC transporters move organic molecules. Thus proton pumping and organelle acidification for low pH depends on V-class proton pump.

Ref: Forgac, Nature Reviews Mol Cell Biol, V-ATPase Structure and Lysosomal Acidification Function.

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