Plasma membrane proton transport release

Although plasma membrane monoamine transporters are responsible for the reuptake of neurotransmitters from the synapse, vesicular monoamine transporters (VMAT) sequester monoamines into synaptic vesicles in preparation for fusion with the plasma membrane and release into the synapse (Schuldiner et ah, 1995). Vesicular uptake is coupled to a proton gradient across the vesicle membrane rather than the sodium gradient used with the plasma membrane transporters (Schuldiner et ah, 1995). These vesicular transporters are not neurotransmitter-speciflc rather, they transport the monoamines nonselectively (Johnson, Jr., 1988 Henry et ah, 1998). 

Figure 6. Scheme to represent known aspects of the plasma membrane NADH oxidase and its association with proton release. The oxidase is activated when hormones or ferric transferrin bind receptors. Oxidase may activate tyrosine kinase which can activate MAP kinases to result in phosphorylation of the exchanger leading to Na+/H+ exchange. Oxidation of quinol in the membrane can also release protons to the outside equal to the number of electrons transferred. External ferricyanide can activate electron flow by accepting electrons at the quinone. G proteins (GTP binding proteins) such as ras-activate electron transport and proton release in some way and may be a link to kinase activation (McCormick, 1993). Semiquinone formation in the membrane could lead to superoxide and peroxide formation by one electron reduction of oxygen. 

Electron transport through oxidases in the plasma membrane contributes to, or controls, part of the proton release from the cell. The details of oxidase function and the mechanism of control remain to be elucidated. The NADPH oxidase of neutrophils is a special case in which proton transport is coupled to the cytochrome >557 electron carrier. This type of proton transport has its precedents in the well-characterized proton pumping through electron carriers in mitochondrial and chloroplast membranes and prokaryotic plasma membranes. 

The bulk of transferrin iron is delivered to immature erythroid cells for utilization in heme synthesis. Iron in excess of this requirement is stored as ferritin and hemosiderin. Unloading of iron to immature erythroid cells is by receptor-mediated endocytosis. The process begins in the clathrin-coated pits with the binding of diferric transferrin to specific plasma membrane transferrin receptors that are associated with the HFE protein complex. The next step is the internalization of the transferrin-transferrin receptor-HFE protein complex with formation of endosomes. The iron transporter DMTl present in the cell membrane is also internalized into the endosomes. In the endosomes, a proton pump acidifies the complex to pH 5.4, and by altering conformation of proteins, iron is released from transferrin bound to transferrin receptor... 

In the 1960s, Mitchell showed how the energy released in electron transport is used to pump protons from the matrix side of the inner mitochondrial membrane to the cytoplasm side. The subsequent dissipation of the proton gradient, via gates in the stalks of the knoblike projections of the inner membrane, activate ATP synthetase. Recently ascorbic acid has been implicated in such membrane potentiation by the establishment of proton gradients in the plasma membrane vesicles extracted from the soybean (Glycine max). 

Plasma membranes of all cells investigated so far contain an electron transport system transferring electrons from NADH to an extracellular electron acceptor (for review, see Navas et al., 1994 and Chapter 4 of this volume). Electron transport across the plasma membrane is accompanied by release of protons from the cell, presumably due to an activation of the Na+/H+ antiport (Sun et a/., 1988). Since proton release and the concomitant increase in cytoplasmic pH have been connected to growth stimulation (Moolenar et al., 1983), it was proposed that the transplasma membrane redox system via proton release might also be involved in the regulation of proliferation. 

In the complete oxidation of fuel molecules relatively little ATP is produced directly by substrate-level phosphorylation (Section 12.5). Irrespective of the metabolic fuel (carbohydrates, fatty acids or amino acids), most of the ATP is derived from the electrons released on the reoxidation of coenzymes, NADH or FADHj. During dehydrogenase-catalysed reactions, electrons are removed from substrates and transferred to coenzymic acceptors which in turn deliver the electrons to an organization of numerous proteins, called an electron-transport assembly. These assemblies are located in the inner membrane of mitochondria, in chloroplast thylakoids (Section 9.5) or in the plasma membrane of bacteria. Electrons are passed along the assembly to molecular oxygen, the final acceptor, which is reduced in the presence of protons to water. During their transfer from component to component, a portion of their energy is released and may be conserved by utilization in the phos-... 

The Tf-TfR cycle. The plasma protein Tf binds to two ferric iron with high affinity. Once Tf-Fe is recognized by its receptor, TfR, it triggers endocytosis. The internalized vesicles become acidified by the proton pump. As the pH decreases in the endosomes, the structure of Tf-TfR complex changes and ferric iron releases. The newly identified endosomal reductase, STEAP3 converts ferric iron to the ferrous form, which is then transported out of endosomes. The fate of the iron after it leaves the endosomes is less well known. Eventually, iron will be used for metabolic processes, such as heme protein synthesis and iron-sulfur (Fe-S) assembly. The apo-Tf TfR will be recycled to the cell membrane. 

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