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Membrane Carriers And Forms Of Transport Notes

Pharmacology Notes > BIOL21141 Cell Membrane Structure & Function Notes

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Topic 5 - Membrane Carriers and Forms of Transport

Active Transport

The hydrolysis of ATP provides energy to move ions against energetically unfavourable gradients. The protein binds to the molecule to be transported on one side of the membrane, undergoes a conformational change and then releases it on the other side.

Primary Active Transporters - In Primary Active Transporters the energy is derived directly from the breakdown of ATP. 80% of all energy goes on Active Transport.

Secondary Active Transporters - In Secondary Active Transporters thee energy is derived secondarily from the energy that was stored in the form of an ionic concentration differences between the two sides of the membrane.

Primary Active Transporter Types 1) P-Type ATPases (E1-E2 ATPases) - This is a large group of evolutionarily related ion and liquid pumps.

Na/K ATPase - This is a solute pump which pumps 3x Na+ out and 2x K+ in, so there is a new export of a single positive charge per pump cycle.

2) V-type H+ ATPase - This is a highly conserved ancient enzyme with extremely diverse functions in eukaryotes. They acidify a wide range of intracellular organelles by pumping protons across the membrane of many cell types. It is regarded as the opposite of ATP Synthase, as it uses ATP hydrolysis for the movement of H+.
3) F-Type ATPase (ATP Synthase) - This uses a proton gradient to drive ATP synthesis by allowing the passive flux of protons across the membrane down their electrochemical gradient. This uses the energy released by the transport reaction to form new ATP molecules.

Na+/K+ ATPase

Na+/K+ ATPase is the sodium pump and the hydrolysis of ATP provides the energy for active transport.
It is the most important pump in animal cells and is responsible for the inward Na+ gradient that drives many secondary active processes.

The Na+/K+ ATPase is a heterodimeric protein with both α and β subunits, with multiple isoforms of each.

1) The cycle begins in the E1 conformation, with ATP bound and sites facing inward.
2) 3x Na+ ions bind, and ATP hydrolysis occurs, phosphorylating the α subunit, and resulting in a conformational change to the E2 state, allowing the Na+ to leave.
3) Once the Sodium (Na+) has left, the site is empty and 2x K+ are able to bind. (The drug Ouabin can lock conformation here to inhibit it.)
4) The K+ binding causes dephosphorylation to occur and ATP binding can allow it to revert to the E1 conformation and the K+ can leave. P-Type in SERCA and Stomach
SERCA (Sarco/endoplasmic Reticulum) Ca2+- ATPase

When muscle contraction occurs, it causes Ca2+ to be released, and this must reuptaken after.
The P-type ATPase sequests Ca2+ back into the Sarcoplasmic Reticulum, and so P-Type ATPases are heavily involved in muscular movement.

Stomach H+/K+ ATPase

The P-Type ATPases in the stomach are proton pumps to lower the pH of the stomach.
This can act as an important site of drug action to inhibit the P-type ATPases in multiple diseases.

V-Type ATPases

V-Type ATPases acidify a wide array of intracellular organelles and pump protons across the plasma membrane of numerous cell types.
V-type ATPases are crucial in renal proton secretion, and this is highlighted by the disease distal renal tubular acidosis that can occur if this process doesn't occur properly.

F-Type ATPases (ATP Synthase)

The hydrogen gradient generated previously is used to synthesise ATP, and all our energy is derived through proton gradients.
The F-type ATPases are located in the mitochondria and have their own DNA.

Bacteriorhodopsin and Photosynthesis

Other means of energy generation include the use of Bacteriorhodopsin and Photosynthesis.

Bacteriorhodopsin - This is a light driven proton-pump which generates a hydrogen gradient to generate energy. This occurs through chemiotactic coupling between the sun energy, bacteriorhodopsin and phosphorylation by ATP synthase during photosynthesis in halophilic bacteria.

Photosynthesis - ATP synthase is central to photosynthesis and once again light can be converted into energy alongside water.

Facilitated Diffusion

Facilitated Transport is the process of binding to a molecule, and once bound a conformational change occurs, allowing the molecule to switch to the other side.
The binding is dependent upon the concentration of the molecule, and this process is passive and down the concentration gradient.

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