ATP Synthase

The ATPase Family

ATPases are membrane-bound ion channels (actually transporters, as they are not true ion channels) that couple ion movement through a membrane with the synthesis or hydrolysis of a nucleotide, usually ATP. Different forms of membrane-associated ATPases have evolved over time to meet specific demands of cells. These ATPases have been classified as F-, V-, A-, P- and E-ATPases based on functional differences. They all catalyse the reaction of ATP synthesis and/or hydrolysis. The driving force for the synthesis of ATP is the H⁺ gradient, while during ATP hydrolysis the energy from breaking the ATP phosphodiester bond is the driving force for creating an ion gradient. Structurally these ATPases can differ: F-, V- and A-ATPases are multi-subunit complexes with a similar architecture and possibly catalytic mechanism, transporting ions using rotary motors. The P-ATPases are quite distinct in their subunit composition and in the ions they transport, and do not appear to use a rotary motor. The different types of ATPases are discussed below:

F-ATPases

The F-ATPases (for ‘phosphorylation Factor’, and also known as H⁺-transporting ATPases or F(0)F(1)-ATPases) are the prime enzymes used for ATP synthesis, and are remarkably conserved throughout evolution. They are found in the plasma membranes of bacteria, in the thylakoid membranes of chloroplasts, and in the inner membranes of mitochondria. These membrane proteins can synthesize ATP using a H⁺ gradient, and work in the reverse to create a H⁺ gradient using the energy gained from the hydrolysis of ATP. In certain bacteria, Na⁺-transporting F-ATPases have also been found.

V-ATPases

V-ATPases (for ‘Vacuole’) are found in the eukaryotic endomembrane system (vacuoles, Golgi apparatus, endosomes, lysosomes, clathrin-coated vesicles {transport external substances inside the cell}, and plant tonolplasts), and in the plasma membrane of prokaryotes and certain specialised eukaryotic cells. V-ATPases hydrolyse ATP to drive a proton pump, but cannot work in reverse to synthesize ATP. V-ATPases are involved in a variety of vital intra- and inter-cellular processes such as receptor mediated endocytosis, protein trafficking, active transport of metabolites, homeostasis and neurotransmitter release

A-ATPases

A-ATPases (for ‘Archaea’) are found exclusively in Archaea and have a similar function to F-ATPases (reversible ATPases), even though structurally they are closer to V-ATPases. A-ATPases may have arisen as an adaptation to the different cellular needs and the more extreme environmental conditions faced by Archaeal species.

P-ATPases

P-ATPases (also known as E1-E2 ATPases) are found in bacteria and in a number of eukaryotic plasma membranes and organelles. P-ATPases function to transport a variety of different compounds, including ions and phospholipids, across a membrane using ATP hydrolysis for energy. There are many different classes of P-ATPases, each of which transports a specific type of ion: H⁺, Na⁺, K⁺, Mg²⁺, Ca²⁺, Ag⁺ and Ag²⁺, Zn²⁺, Co²⁺, Pb²⁺, Ni²⁺, Cd²⁺, Cu⁺ and Cu²⁺. For example, gastric P-ATPase is a H⁺/K⁺ pump responsible for acid secretion in the stomach, transporting H⁺ from the cytoplasm of stomach parietal cells to create a large pH gradient in exchange for getting K⁺ ions inside the cell, using ATP hydrolysis as the energy source. P-ATPases can be composed of one or two polypeptides (fewer than the other ATPases), and can assume two conformations called E1 and E2.

E-ATPases

E-ATPases (for ‘Extracellular’) are membrane-bound cell surface enzymes that have broad substrate specificity, hydrolysing other NTPs besides ATP, as well as NDPs – although their most likely substrates are ATP, ADP and UTP, as well as extracellular ATP. There are at least three classes of E-ATPases: ecto-ATPases, CD39s, and ecto-ATP/Dases. An example is ecto-ATPase from the smooth muscle membranes of chickens, which is thought to exhibit a range of activities determined by the oligomerisation of the enzyme, which in turn is affected by different membrane events.