Cells proton gradients

In 1961, Peter Mitchell, a British biochemist, proposed that the energy stored in a proton gradient across the inner mitochondrial membrane by electron transport drives the synthesis of ATP in cells. The proposal became known as... 

In resting muscle the high concentration of ADP does not decrease the proton gradient effectively and the high membrane potential slows electron transport. ADP, formed when ATP is hydrolyzed by myosin ATPase during contraction, may stimulate electron transport. However, the concentration of ATP (largely as its Mg salt) is buffered by its readily reversible formation from creatine phosphate catalyzed in the intermembrane space, and in other cell compartments, by the various isoenzymes of creatine kinase (reviewed by Walliman et al., 1992). 

Aerobic respiration. Many organisms carry out aerobic respiration in which enzymes remove electrons from organic compounds and pass them through a chain of carriers including flavoproteins and cytochromes located in intracellular membranes (Fig. 3-4) until finally they are used to reduce oxygen to produce water. ATP is produced by an enzyme called ATPase, that is located in the cell membrane, and the process is driven by a proton gradient across the membrane. 

Fig. 3-4 Electron transport process schematic, showing coupled series of oxidation-reduction reactions that terminate with the reduction of molecular oxygen to water. The three molecules of ATP shown are generated by an enzyme called ATPase which is located in the cell membrane and forms ATP from a proton gradient created across the membrane.

Spanning the membrane are ATP synthase complexes that use the potential energy of the proton gradient to synthesize ATP from ADP and P,. In this way, oxidation is closely coupled to phosphorylation to meet the energy needs of the cell. 

Reserpine irreversibly inhibits the triphosphatase that maintains the proton gradient and so it depletes neurons of their vesicular store of transmitter. This explains why restoration of normal neuronal function rests on delivery of new vesicles from the cell bodies. Some amphetamine derivatives, including methylenedioxymethamphetamine (MDMA), are also substrates for the transporter and, as a result, competitively inhibit noradrenaline uptake. Another way of inhibiting the transporter is by dissipation of the pH gradient across the vesicular membrane i-chloroamphetamine is thought to act in this way. 

Recent studies by Crompton et al. have shown that oxidant stress may open a Ca-sensitive, non-selective pore in the inner mitochondrial membrane that is blocked by cyclosporin A (Crompton, 1990 Crompton and Costi, 1990). This pore opening results in massive mitochondrial swelling, dissipation of the transmembrane proton gradient and disruption of mitochondrial energy production (Crompton et al., 1992). Since mitochondria may play a role as a slow, high-capacity cytosolic calcium buffer (Isenberg et al., 1993), disruption of mitochondrial function may also contribute to calcium overload and cell injury. 

The proton gradient like the gradients of any other ions, which are established across membranes, as well as the ATP can be used to drive exchange with other ions or to drive uptake of molecules. In cells, uptake driven by H+ and Na+ gradients and ATP are common throughout evolution. 

I. Freund, and B. Wolf, Non-invasive measurement of cell membrane associated proton gradients by ion-sensitive field effect transistor arrays for microphysiological and bioelectronical applications. Biosens. Bioelectron. 15, 117-124 (2000). 

FIGURE 13-6 The substituted amphetamine fenfluramine inhibits the transport of 5-HT by both (A) the vesicular transporter, and (B) the serotonin transporter (SERT). Substituted amphetamines such as fenfluramine and MDMA stimulate the release of 5-HT from serotonergic terminals. These drugs block the vesicular transporter and disrupt the proton gradient across the vesicle membrane. The increase in intracellular 5-HT favors the release of 5-HT by the reverse action of the SERT. These drugs also act as substrates for the SERT so as to inhibit the transport of 5-HT into cells. 

In bacteria and yeasts, Li+ has strain-dependent, inhibitory, and morphological effects upon growth. The driving force behind the transport of carbohydrates and amino acids in bacteria is the proton gradient, and in both E. coli [228] and Salmonella typhimurium cells [229], Li+ stimulates the movement of proline into cells via a Li+/proline symport and the transport of melibiose via a cotransport pathway [230]. In both cases, Li+ is replacing Na+ and results in the inhibition of growth. 

It shows a section through a bacterial cell (only one corner of the cell is shown). ATP synthase links the discharge of the transmembrane proton gradient to the formation of ATP, A simple mechanism (hydrogen cycling) B. a mechanism in which the membrane-bound electron-transfer proteins are proton pumps. 

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