Chemiosmosis

Overview
Chemiosmosis is the diffusion of ions across a selectively-permeable membrane. More specifically, it relates to the generation of ATP by the movement of hydrogen ions across a membrane during cellular respiration.



Hydrogen ions (protons) will diffuse from an area of high proton concentration to an area of lower proton concentration. Peter Mitchell proposed that an electrochemical concentration gradient of protons across a membrane could be harnessed to make ATP. He likened this process to osmosis, the diffusion of water across a membrane, which is why it is called chemiosmosis.

ATP synthase is the enzyme that makes ATP by chemiosmosis. It allows protons to pass through the membrane using the kinetic energy to phosphorylate ADP making ATP. The generation of ATP by chemiosmosis occurs in chloroplasts and mitochondria as well as in some bacteria.

The Chemiosmotic Theory
Peter D. Mitchell proposed the chemiosmotic hypothesis in 1961. The theory suggests essentially that most ATP synthesis in respiring cells comes from the electrochemical gradient across the inner membranes of mitochondria by using the energy of NADH and FADH2 formed from the breaking down of energy rich molecules such as glucose. Molecules such as glucose are metabolized to produce acetyl CoA as an energy-rich intermediate. The oxidation of acetyl CoA in the mitochondrial matrix is coupled to the reduction of a carrier molecule such as NAD and FAD. The carriers pass electrons to the electron transport chain (ETC) in the inner mitochondrial membrane, which in turn pass them to other proteins in the ETC. The energy available in the electrons is used to pump protons from the matrix across the inner mitochondrial membrane, storing energy in the form of a transmembrane electrochemical gradient. The protons move back across the inner membrane through the enzyme ATP synthase. The flow of protons back into the matrix of the mitochondrion via ATP synthase provides enough energy for ADP to combine with inorganic phosphate to form ATP. The electrons and protons at the last pump in the ETC are taken up by oxygen to form water.

This was a radical proposal at the time, and was not well accepted. The prevailing view was that the energy of electron transfer was stored as a stable high potential intermediate, a chemically more conservative concept.

The problem with the older paradigm is that no high energy intermediate was ever found, and the evidence for proton pumping by the complexes of the electron transfer chain grew too great to be ignored. Eventually the weight of evidence began to favor the chemiosmotic hypothesis, and in 1978, Peter Mitchell was awarded the Nobel Prize in Chemistry.

Chemiosmotic coupling is important for ATP production in chloroplasts and many bacteria.

The proton-motive force
In all cells, chemiosmosis involves the proton-motive force (PMF) in some step. This can be described as the storing of energy as a combination of a proton and voltage gradient across a membrane. The chemical potential energy refers to the difference in concentration of the protons and the electrical potential energy as a consequence of the charge separation (when the protons move without a counter-ion).

In most cases the proton motive force is generated by an electron transport chain which acts as both an electron and proton pump, pumping electrons in opposite directions, creating a separation of charge. In mitochondria free energy released from the electron transport chain is used to move protons from the mitochondrial matrix to the intermembrane space of the mitochondrion. Moving the protons to the outer parts of the mitochondrion creates a higher concentration of positively charged particles, resulting in a slightly positive, and slightly negative side (then electrical potential gradient is about -200 mV (inside negative). This charge difference results in an electrochemical gradient. This gradient is composed of both the pH gradient and the electrical gradient. The pH gradient is a result of the H+ ion concentration difference. Together the electrochemical gradient of protons is both a concentration and charge difference and is often called the proton motive force (PMF). In mitochondria the PMF is almost entirely made up of the electrical component but in chloroplasts the PMF is made up mostly of the pH gradient.  In either case the PMF needs to be about 50 kJ/mol for the ATP synthase to be able to make ATP.

In mitochondria
The complete breakdown of glucose in the presence of oxygen is called cellular respiration. The last steps of this process occur in the mitochondria. High energy molecules NADH and FADH2 are generated by the Krebs cycle and glycolysis. These molecules dump electrons onto an electron transport chain to create a proton gradient across the inner mitochondrial membrane. ATP synthase is then used to generate ATP by chemiosmosis. This process is called oxidative phosphorylation because oxygen is the final electron acceptor in the mitochondrial electron transport chain.

Chemiosmotic phosphorylation is the third, and final, biological pathway responsible for the production of ATP from an inorganic phosphate and an ADP molecule via oxidative phosphorylation.

Occurring in the mitochondria of cells, the chemical energy of NADH, produced in the Krebs Cycle is used to build up a gradient of hydrogen ions (protons), with a higher concentration present in the mitochondrial cristae and a lower concentration in the mitochondrial matrix. This is the only step of oxidative phosphorylation for which oxygen is required: oxygen is used as an electron acceptor, combining with free electrons and hydrogen ions to form water.

In plants
The Light reactions of photosynthesis generate energy by chemiosmosis. Chlorophyll loses an electron when energized by light. This electron travels down a photosynthetic electron transport chain ending on the high energy molecule NADPH. The electrochemical gradient generated across the thylakoid membrane drives the production of ATP by ATP Synthase. This process is known as photophosphorylation.

In prokaryotes
Bacteria and archaea also can use chemiosmosis to generate ATP. Cyanobacteria, green sulfur bacteria, and purple bacteria create energy by a process called photophosphorylation. These bacteria use the energy of light to create a proton gradient using a photosynthetic electron transport chain. Non-photosynthetic bacteria such as E. coli also contain ATP synthase.

In fact, mitochondria and chloroplasts are believed to have been formed when early eukaryotic cells ingested bacteria that could create energy using chemiosmosis. This is called the endosymbiotic theory.

Other references

 * biochemistry textbook reference, from the NCBI bookshelf &mdash;
 * technical reference relating one set of experiments aiming to test some tenets of the chemiosmotic theory &mdash;

Chemiosmotische Kopplung Chemiosmoza Quimiosmosis