Proton
Protons are accelerated to 12 GeV in a synchrotron in which the bending magnets have a maximum field strength of 14.3 T. What is the radius of curvature of the proton orbit?
From: Radiochemistry and Nuclear Chemistry (Third Edition), 2002
Related terms:
Inorganic Ions
Magnetic Resonance Imaging
Enzyme
Protein
Hydrogen
Carbon 13
Nuclear Magnetic Resonance
Proton Nuclear Magnetic Resonance
Adenosine Triphosphate
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Digestion and absorption
Martin Kohlmeier, in Nutrient Metabolism, 2003
Molecular mechanisms of nutrient transport
Paracellular diffusion: Water, some inorganic ions, and a few other very small compounds can bypass the intestinal cells altogether by traveling (in either direction) through very narrow (4–8 Å) pores of the tight junctions sealing the spaces between enterocytes. The tight junctions of the proximal small intestine consist of fewer strands of sealing proteins with pore sizes of about 8 Å and are therefore more permeable than distal intestinal segments with tight junction pore sizes of only 4 Å.
Active ATP-driven transport: Several ATP-hydrolyzing complexes transport nutrients across luminal, intracellular, and basolateral membranes. Crossing intracellular membranes is often necessary to move molecules out of endosomes/lysosomes, across the inner mitochondrial membrane or into secretory compartments. There is a group of nearly fifty ATP-binding cassette transporters (ABC transporters) that use the energy from ATP hydrolysis to move medium-sized molecules across membranes or to adjust their shape for regulatory purposes. Several are critical for intestinal absorption, such as CFTR (ABCC7) for the regulation of chloride secretion, the ABC transporters Al and G5/G8 for the control of cholesterol absorption efficiency, and multidrug resistance protein 2 (MRP2; ABCC2) for folate export across the basolateral membrane.
Then there are highly specialized ATPases for the absorption of copper and calcium. Menkes protein (ATP7A; EC3.6.3.4) transports copper into secretory vesicles for export into blood. The calcium-transporting ATPase lb (plasma membrane calcium-pumping ATPase 1b, PMCA1b; EC3.6.3.8) moves calcium directly across the basolateral membrane.
The ATPases that pump sodium and potassium do the really heavy lifting in nutrient absorption. The sodium/potassium-exchanging ATPase (EC3.6.3.9) labors at the basolateral membrane of all enterocytes throughout the small and large intestines. Each ATP-hydrolyzing cycle pumps three sodium ions out of the cell into basolateral space and pulls in two potassium ions in exchange. This establishes the low intracellular sodium concentration (Zuidema et al., 1986) that is the main driving force for active nutrient transport.
Sodium cotransport: Specific transporters use the electrochemical potential by firmly coupling the movement of the nutrient ligand to that of sodium along the steep sodium gradient. Examples for sodium-driven bulk transporters are the sodium-glucose transporter 1 (SLC2A2) and the amino acid transport system Bo (ASCT2, SLC1A5), which every day move several hundred grams of nutrients plus several liters of water out of the small intestinal lumen. It should be noted that similar cotransporters at the basolateral membrane allow postprandial nutrient flux from the enterocytes towards the blood capillaries, and also in the opposite direction during fasting, to supply nutrients for the enterocyte's own considerable needs.
Proton cotransport: The sodium/hydrogen exchanger 3 (NHE3, SLC9A3) at the luminal side and the sodium/hydrogen exchanger 2 (NHE2, SLC9A2) at the basolateral side move protons out of the enterocytes and establish a significant proton gradient. Hydrogen ions (protons) can then drive nutrient cotransport just like sodium ions do. Examples of proton-driven transporters are the monocarboxylic acid transporter 1 (MCT1, SLC16A1) for lactate, pyruvate, acetate, propionate, benzoate, and nicotinate (Orsenigo et al., 1999) and the hydrogen ion/peptide cotransporter 1 (PepT1, SLC15A1).

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Figure 4.2. The sodium gradient established by sodium-potassium ATPase drives nutrient transport from the intestinal lumen into enterocytes
Chloride cotransport: The taurine transporter (TAUT, SLC6A6) uses the chloride gradient in the ileum for the uptake of taurine from bile acids.
Exchangers: Some transporters function in such a way that a mass gradient pushes another type of molecule in the opposite direction. The above-mentioned sodium-hydrogen exchangers, for instance, use the gradient-driven inward movement of sodium to push protons out of the cell. Another example is the putative anion transporter 1 (PAT1, SLC26A6) in the proximal small intestine, which very effectively couples the recovery of chloride with the countertransport of bicarbonate for neutralizing gastric (hydrochloric) acid. A group of membrane-anchored glycoproteins at both sides of the enterocytes uses neutral amino acids to move other amino acids in the opposite direction. This means that alanine (or another neutral amino acid consumed in bulk), whose intracellular concentration increases after a meal due to uptake via the sodium-driven transport system Bo, moves back into the intestinal lumen to drive cystine (oxidized cysteine) into the cell. The alanine is then, of course, taken up again via system B∘.
Facilitated diffusion: Several transporters mediate the selective transfer of nutrients along their concentration gradient. Important examples are the transporter for fructose (GLUT5, SLC2A5) on the luminal side of the proximal small intestine, and the glucose transporter 2 (GLUT2, SLC2A2) at the basolateral side. GLUT2 also serves nutritive functions for enterocytes as mentioned above for the sodium-driven amino acid transporters.
Intracellular transformation: Phosphorylation or other chemical changes commonly take place after the uptake of nutrients to prevent them from returning into the intestinal lumen by the way they entered. The absorption of vitamin B6 provides an example for such 'trapping.' The pyridoxin carrier accepts only free pyridoxin, and conversion to pyridoxin phosphate keeps the equilibrium always in favor of the influx direction.
Nutrients also are metabolized to provide energy and material for the needs of the rapidly proliferating intestinal cells. Glutamine, for example, is a major energy fuel as well as nitrogen source for the intestines. Some glutamine in enterocytes is also used for the synthesis of ornithine and citrulline, which is exported for use in the urea cycle of liver and kidneys and for the arginine synthesis. Thus, only some of the absorbed glutamine reaches blood circulation.
Unmediated transcellular diffusion: Very few compounds can directly cross the formidable barrier of the bilayer membranes on the apical and basolateral sides of the cells lining the intestinal lumen. These are mainly small lipophilic compounds, urea and gases (hydrogen, methane, hydrogen sulfide).
Transcytosis: The brush border membrane folds in and connects to vesicular structures of the endosomal compartment that also provides a secretory pathway on the basolateral side. This endosomal mechanism can transport intestinal peptide hormones as well as small amounts of ingested proteins and peptides (Ziv and Bendayan, 2000). Transcytosis explains how cow milk protein or gluten can evade intracellular catabolism.
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Channels
K.B. Hansen, ... S.F. Traynelis, in Comprehensive Biophysics, 2012
6.2.2.8 Protons Acting as Negative Allosteric Modulators
Proton sensitivity is a feature shared across the entire glutamate receptor family that could have important effects during normal synaptic activity, glutamate release, glutamate uptake, stroke, and seizure – processes all known to alter the extracellular pH.49 Protonation of glutamate receptors in some way prevents opening of the receptor gate.49 The proton IC50 varies with the glutamate receptor subunit, with IC50 values near physiological pH for the NMDA receptor, leading to the idea of tonic proton inhibition.230 Proton inhibition depends on splicing of RNA encoding the GluN1 N-terminal domain.230 At the single channel level, protons reduce open probability of GluN2B subunit-containing NMDA receptors, with modest effects on open duration and single channel conductance; proton inhibition is independent of agonist binding and voltage.231,232 Mutagenesis data have revealed that the residues that mediate pH sensitivity are clustered close to the gate and the ligand binding domain dimer interface.12,124,233 Interestingly, the trapping channel blocker MK801, which facilitates channel closing, can sense the protonation state of the receptor, supporting the idea of a tight coupling between protons and gating.
AMPA receptors are also sensitive to the extracellular proton concentration in a voltage-independent manner. Protons inhibit AMPA receptor function by enhancing receptor desensitization and reducing the open probability.227,228 Extracellular protons also inhibit recombinant and native kainate receptors in a voltage-independent manner without effects on desensitization.234 The IC50 values for proton inhibition of recombinant GluK1 and GluK2 correspond to pH 6.9, suggesting that kainate receptors are also under some degree of tonic inhibition at physiological pH. Heteromeric receptors containing GluK5 show reduced proton sensitivity, whereas GluK2/GluK4 receptors are potentiated by extracellular protons.234 Mutant Lurcher GluD2 receptors are also inhibited by protons in a voltage-independent manner.235
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Antigen Binding Molecules: Antibodies and T-cell Receptors
Harden M. McConnell, Maria Martinez-Yamout, in Advances in Protein Chemistry, 1996
IV. Selective Deuteration
Proton difference spectra for antibody combining sites contain so many resonance signals that it is difficult to resolve the resonance line of individual protons in amino acids. Difference spectra can be significantly simplified by amino acid deuteration (Anglister, 1990). Antibody-secreting hybridomas can be grown on selectively deuterated amino acids, and these amino acids can be incorporated to a level of over 95% in the secreted antibody (see Anglister et al., 1984a,b; see also Gettings and Dwek, 1981). In a number of studies, partially deuterated tyrosine residues, illustrated in Fig. 4, have been employed. Partial deuteration of antibody proteins sometimes provides a second advantage, significantly decreasing the NMR line widths of the remaining proton signals. The proton signals in Fig. 3 arise from the protons in tyrosine that are next to the hydroxyl group. When there is rapid flipping of the tyrosine aromatic side chain, the two protons on a given residue are equivalent on the NMR time scale and give resonance signals at the same position. Flipping of the tyrosine aromatic ring at a rate of ≥10 sec−1 produces this equivalence. As a rule, solvent-exposed tyrosine residues undergo this rapid flipping.

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Fig. 4. Partially deuterated tyrosine. Spectra reported here arise from H-3,5-tyrosine.
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Proton Therapy
Radhe Mohan PhD, ... Andrew K. Lee MD, MPH, in Leibel and Phillips Textbook of Radiation Oncology (Third Edition), 2010
Treatment Safety
Proton treatment delivery systems should, at a minimum, meet the same quality and safety standards as photon systems. Daily pretreatment quality assurance tests should include standard output checks; functional safety features, including the treatment room door interlock; and alignment between the proton beam and the x-ray systems. One interesting difference between proton and photon treatment rooms is that the proton room may consist of three separate spaces, namely the treatment room, the space behind the treatment room (which contains the gantry and electronics), and the space dedicated to x-ray imaging. Thus, proton facilities generally have a room-sweeping alarm, which must be activated before the treatment door is closed, to alert anyone in any space inside the room that radiation will commence soon. This alarm system should be tested every treatment day.
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Voltage-Gated Proton Channels☆
Y. Okamura, in Reference Module in Life Sciences, 2017
Abstract
Protons play fundamental roles in biological functions such as in bioenergetics, motility, secretion, and host defense. Voltage-gated proton channels (Hv channels) exhibit strict ion selectivity and voltage dependence similar to other voltage gated ion channels, including voltage gated sodium, potassium and calcium channels. However, Hv channels show several distinct features; their permeant ions are protons which at physiological pH exist at a concentration lower by several orders of magnitude than sodium or potassium and their voltage-dependent gating is regulated by pH gradient. A protein, called Hv1 or VSOP (voltage sensor domain only protein), contains a voltage sensor domain (VSD) but lacks a separate pore domain. It exhibits activities of voltage-dependent proton current. Thus, in the Hv channel, the VSD has dual roles: voltage sensing and proton permeation.
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Basics of Radiation Therapy
Elaine M. Zeman, ... Joel E. Tepper, in Abeloff's Clinical Oncology (Sixth Edition), 2020
Protons
Protons are charged particles that can be accelerated and directed into tissue where they deposit their energy. Proton therapy is the most common type of heavy particle radiation therapy. The advantage that protons have over conventional x-rays is that they deliver a low dose to superficial (normal) tissues, a high radiation dose at depth where the tumor is, and then virtually no exit dose to normal tissues beyond the tumor. This is the opposite of what happens with x-rays, where the highest dose (from a single beam) is delivered to more superficial tissues. The RBE for protons is approximately 1.1, so they are only slightly more biologically effective than x-rays or electrons; this means that the principal advantage of proton therapy is improved dose distributions.
Proton beams are produced by accelerating ionized hydrogen in a cyclotron or synchrotron to energies in excess of 160 MeV. These machines are considerably larger and more expensive than conventional linear accelerators, so they tend to be incorporated into stand-alone facilities (although research into smaller-scale proton irradiators is ongoing). Unlike electrons, which lose energy roughly evenly across the range of therapeutic energies, protons lose their energy at an increasing rate as the beam loses energy with depth. This effect culminates in a region of rapid dose deposition near the depth of maximum penetration, called the Bragg peak (see Fig. 27.25). The depth of the Bragg peak increases with beam energy, allowing careful energy selection to ensure that the highest dose is delivered to the tumor volume, with lower doses upstream of the target, and negligible doses downstream of the target. The width of the Bragg peak is virtually always narrower than the region to be targeted, requiring a range of proton energies to "paint" high, uniform doses across the target. This widened dose distribution, known as a spread-out Bragg peak (SOBP), can be created either by varying the proton beam energy in a synchrotron or by using a spinning modulator of varying thickness to selectively vary the beam energy, shown in Fig. 27.26.
The largest clinical experience with the use of proton radiation therapy has been for the treatment of prostate cancer. However, although there is a theoretical advantage of proton therapy at this site, that advantage has never been demonstrated through clinical trials.164 Protons are very appealing for the treatment of certain pediatric tumors because the effects of unwanted irradiation of normal tissues can be severe. In this context, protons have been used extensively in the treatment of pediatric central nervous system tumors.165 Studies exploring the use of protons for therapy of lung cancer and tumors at other anatomic sites are ongoing. The cost of a proton irradiator (and its specialized facility) is far greater than for traditional x-ray and electron linear accelerators, so it is incumbent on those who use protons for radiation therapy to demonstrate that the extra expense translates into better tumor control rates and/or fewer normal tissue complications. The lack of such Level I evidence to date has made many concerned about the rapid proliferation of proton facilities.
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Macromolecule–Ligand Interactions Studied by NMR
J. Feeney, in Encyclopedia of Spectroscopy and Spectrometry (Third Edition), 2017
Dissociation Rate Constants from Transfer of Saturation Studies
If protons are present in two magnetically distinct environments, for example one corresponding to the ligand free in solution and the other to the ligand bound to the protein, then under conditions of slow exchange separate signals are seen for the protons in the two forms. When the resonance of the bound proton is selectively irradiated (saturated), its saturation will be transferred to the signal of the free proton via the exchange process and the intensity of the free proton signal will decrease. The rate of decrease of the magnetization in the free state as a function of the irradiation time of the bound proton can be analysed to provide the dissociation rate constant. This method has been used to measure the dissociation rate constant for the complexes of NADP+. DHFR (20 s−1 at 284 K) and trimethoprim. DHFR (6 s−1 at 298 K). 2D-NOESY/EXCHANGE type experiments can also be used for such measurements.
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Magnetic Resonance Imaging in Osteoarthritis
Timothy Mosher, in Osteoarthritis, 2007
Proton Density
Although all protons generate an MRI signal, only those protons located on molecules with sufficient mobility contribute to the signal detected by the MRI receiver (which is converted into an image). Protons located on large macromolecules (such as proteins or nucleic acids) have limited motion and lose signal before they can be detected. However, these molecules can contribute significantly to image contrast through interactions with nearby mobile protons (discussed further later in the chapter). The density of mobile protons in a voxel is a primary source of contrast in the MR image. Tissues with a high concentration of mobile protons (such as synovial fluid) can generate a strong MRI signal, whereas tissues with a low mobile-proton concentration (such as cortical bone and fibrous tissue) generate a weak signal and appear dark on images obtained with standard clinical MRI techniques.