Cytochrome oxidase (Figure 6a and 6b) is the best understood of all the electron-carrier proteins involved in oxidative phosphorylation. Regulation of this important pathway is, however, still not understood, largely due to limitations in the ability to measure the essential metabolites, including oxygen (pO2, oxygen pressure), ADP, and AMP. Letter to the Editor: Mitochondrial cytochrome c oxidase: mechanism of action and role in regulating oxidative phosphorylation. Epub 2017 Oct 29. The rate of electron transfer through the complex is primarily controlled by the associated thermodynamic forces, i.e., the span in redox potential between oxygen and cytochrome c and the protonmotive force. 2020 May 8;295(19):6357-6371. doi: 10.1074/jbc.RA119.010593. J Biol Chem. Cytochrome c oxidase, which catalyzes an irreversible step of the respiratory chain, is one of the rate‐controlling steps of oxidative phosphorylation on isolated mitochondria. 2014 Dec 15;117(12):1424-30. doi: 10.1152/japplphysiol.00736.2014. Cytochrome c oxidase is responsible for reduction of molecular oxygen to water using reducing equivalents donated by cytochrome c and for site 3 energy coupling in oxidative phosphorylation. An intermediate in the reaction, tentatively identified as peroxide, bridged between the iron and copper atoms of the reaction site has a central role in coupling mitochondrial respiration to the [ATP]/[ADP][Pi]. Rose JJ, Bocian KA, Xu Q, Wang L, DeMartino AW, Chen X, Corey CG, Guimarães DA, Azarov I, Huang XN, Tong Q, Guo L, Nouraie M, McTiernan CF, O'Donnell CP, Tejero J, Shiva S, Gladwin MT. Oxidative phosphorylation takes place in the inner mitochondrial membrane (Figure 32). However, the cell does not release this energy all at once, as this would be an uncontrollable reaction. Electron transport chain and oxidative phosphorylation Last updated: January 14, 2021. Complex III itself is composed of several subunits, one of which is a b-type cytochrome while another one is a c-type cytochrome. Complex III: ubiquinone to cytochrome c Complex III also called cytochrome c – coenzyme Q oxidoreductase Composed of: 2 cytochromes b (b 562 et b 566) 2 proteins with Fe-S clusters 2 cytochrome c 1 Role? Copyright © 2021 Elsevier B.V. or its licensors or contributors. Abstract Life of higher organisms is essentially dependent on the efficient synthesis of ATP by oxidative phosphorylation in mitochondria. A mechanism-based model of the cytochrome c oxidase reaction is presented in which transfer of reducing equivalents from the lower- to the higher-potential region of the coupling site … The Central Role of Glucokinase in Glucose Homeostasis: A Perspective 50 Years After Demonstrating the Presence of the Enzyme in Islets of Langerhans. Many catabolic biochemical processes, such as glycolysis, the citric acid cycle, and beta oxidation, produce the reduced cofactor NADH. Author information: (1)Department of Neurology, Miller School of Medicine Miami, University of Miami, 1420 NW 9th Avenue, TSL Building, Rm. What do the bands show? J Appl Physiol (1985). The mitochondrion has two membranes: an inner membrane and an outer membrane. Asthenozoospermia Staining Cytochrome-c Oxidase 6B2 Immunofluorescent Oxidative Phosphorylation 1. The cytochrome c content was decreased in subsarcolemmal mitochondria after ischemia (ischemia: 0.111 +/- 0.013 vs. control: 0.156 +/- 0.007 nmol/mg protein, P < 0.05). The activities of the electron transport chain (ETC) complexes and the cytochrome content in solubilized mitochondria were measured using spectrophotometric methods. Cytochrome c oxidase is responsible for reduction of molecular oxygen to water using reducing equivalents donated by cytochrome c and for site 3 energy coupling in oxidative phosphorylation. Is oxidative phosphorylation feedback regulated by its end-products? Why is the result important for the physiological role of the post-translational modification? Asthenozoospermia Staining Cytochrome-c Oxidase 6B2 Immunofluorescent Oxidative Phosphorylation 1. Its dysfunction favors the development of hypoxia-dependent pathologies, including ischemia and cancer. Four of the phosphorylations result in inhibition of the apoptotic functions of Cytc, suggesting a cytoprotective role for phosphorylated Cytc. Complex IV. Cytochrome c (Cytc) 1 is a cellular life and death decision molecule that regulates cellular energy supply and apoptosis through tissue specific post-translational modifications. Cell response to physiological changes and oxidative stress involves the modulation of mitochondrial metabolism. The International Journal of Biochemistry & Cell Biology, https://doi.org/10.1016/j.biocel.2020.105704. Get the latest public health information from CDC: https://www.coronavirus.gov, Get the latest research information from NIH: https://www.nih.gov/coronavirus, Find NCBI SARS-CoV-2 literature, sequence, and clinical content: https://www.ncbi.nlm.nih.gov/sars-cov-2/. Cytochrome c(Cyt c), a heme-containing mitochondrial protein, has a critical function in both respiration and apoptosis. The inner membrane is the site of oxidative phosphorylation. Mitochondria are the site of aerobic respiration within the cell. Mechanisms of Novel Host Use by Bactrocera tau (Tephritid: Diptera) Revealed by RNA Transcriptomes.  |  Please enable it to take advantage of the complete set of features! What percent (approximate) of the purified cytochrome C is phosphorylated? Epub 2020 Mar 23. Front Physiol. 2013 Mar;65(3):171-9. doi: 10.1002/iub.1138. The final and rate limiting step of the respiratory chain is cytochrome c oxidase (COX) which represents the regulatory center of OXPHOS. ATP, the universal energy currency in all living cells, is mainly synthesized in mitochondria by oxidative phosphorylation (OXPHOS). What percent (approximate) of the purified cytochrome C is phosphorylated? The complex contains 11 … Hence, from Table 2 below, we see that cytochrome c 1 (part of the cytochrome reductase complex, #3 in Figure 9) can spontaneously transfer an electron to cytochrome c … • Apoptosis can be initiated at the outer mitochondrial membrane by BCL-2 family proteins, leading to increased membrane permeability, release of cytochrome C into the cytoplasm, and activation of cytoplasmic caspases and nucleases. High resolution respirometry analysis of polyethylenimine-mediated mitochondrial energy crisis and cellular stress: Mitochondrial proton leak and inhibition of the electron transport system. Oxidative phosphorylation is a mechanism for ATP synthesis in both plant and animal cells. Oxidative phosphorylation takes place in the inner mitochondrial membrane (Figure 32). Cytc is an electron carrier in the mitochondrial electron transport chain (ETC) and thus central for aerobic energy production. NLM Oxidative phosphorylation occurs in the mitochondria. The cytochrome c content was decreased in subsarcolemmal mitochondria after ischemia (ischemia: 0.111 +/- 0.013 vs. control: 0.156 +/- 0.007 nmol/mg protein, P < 0.05). Complex IV involves transferring two electrons from cytochrome c to molecular oxygen (O 2), the final electron acceptor, thus forming water (H 2 O). 1,2 Mitochondria are oval-shaped organelles, typically about 2um in length and 0.5 um in diameter, and are located outside of the nucleus of the cell. The steady-state rate equation is fitted to data for the dependence of mitochondrial respiratory rate on cytochrome c reduction, oxygen pressure (pO2), and [ATP]/[ADP][Pi] at pH 6.5 to 8.35 (where Pi is inorganic phosphate). Lipid soluble cytochrome c assists in moving electrons between the two complexes. HALLMARK_OXIDATIVE_PHOSPHORYLATION: Systematic name: M5936: Brief description: Genes encoding proteins involved in oxidative phosphorylation. 2019 Jul;26(5):e12497. Complex IV. 4.1 Oxidative Phosphorylation. Mitochondrial oxidative phosphorylation has a central role in eukaryotic metabolism, providing the energy (ATP) required for survival. Oxidative stress response involves redox signals modulating protein phosphorylation (8). USA.gov. This complex contains two heme groups (one in each of the two cytochromes, a, and a 3) and three copper ions (a pair of Cu A and one Cu B in cytochrome a 3). 1992 May 25;267(15):10266-73. 2017 Dec 1;595(23):7023-7038. doi: 10.1113/JP273839. NCI CPTC Antibody Characterization Program. Summary. From there electrons flow to an adjacent heme a (low spin) which transfers them to another heme a3 (high spin) and then finally to dioxygen which is coordinated to the Fe in heme a3 and to an adjacent CuB. Oxidative phosphorylation (OXPHOS) of intact mitochondria and cytochrome c oxidase activity in permeabilized mitochondria were determined with polarographic assays. It is a transmembrane protein with multiple subunits present in the mitochondria of all aerobic eukaryotic organisms and and the cell membrane of almost all bacteria. Copyright © 2014 the American Physiological Society. The fourth complex is composed of cytochrome proteins c, a, and a 3. Complex IV. The fit of the rate expression to the experimental data is very good for all experimental conditions. Succinate is also oxidized by the electron transport chain, but feeds into the pathway at a different point. The free energy of this complete reaction (NADH + H+ + 1/2 O 2-> NAD+ + H 2 O) is -52.6 kcal/mol. Microcirculation. Epub 2018 Oct 10. This article reviews our present knowledge on the structure of bacterial and eukaryotic cytochrome c oxidases and correlates it with recent results on the regulatory functions of nuclear‐coded subunits of the eukaryotic enzyme, which are absent from the bacterial enzyme. Figure: Cytochrome C Oxidase Cytochrome C, the initial “substrate” of this complex, delivers electrons from its heme cofactor to a dinuclear copper cluster, CuA. Oxidative phosphorylation (OXPHOS) of intact mitochondria and cytochrome c oxidase activity in permeabilized mitochondria were determined with polarographic assays. This results in maximal ETC flux during reperfusion, mitochondrial membrane potential hyperpolarization, excessive ROS generation, and apoptosis. We use cookies to help provide and enhance our service and tailor content and ads. A new molecular hypothesis on the physiological regulation of oxidative phosphorylation is proposed, assuming a hormonally controlled dynamic equilibrium in vivo between two states of energy metabolism, a relaxed state with low ROS (reactive oxygen species) formation, and an excited state with elevated formation of ROS, which are known to accelerate aging and to cause degenerative diseases … Levels of the intermediates in oxygen reduction in the oxidase reaction site have been calculated. Center for Molecular Medicine and Genetics, Wayne State University, Detroit, Michigan, USA . Oxidative phosphorylation is maintained by cellular energy requirements. Since the oxidative phosphorylation is a particulate enzyme system, all simulations are carried out for a single cytochrome concentration (cytochrome a, 1 μ m; cytochrome c, 2 μ m). Control by cytochrome coxidase of the cellular oxidative phosphorylation system depends on the mitochondrial energy state Claudia Piccoli, Rosella Scrima, Domenico Boffoli,and Nazzareno Capitanio1 Department of Biomedical Science, University of Foggia, 71100 Foggia, Italy 1To whom correspondence should be addressed (email ti.gfinu@pac.n). Background About half of infertility in couples relates to the male factor, and asthenozoospermia (astheno) is a common defect in male fertility, with a prevalence … 2001 Sep-Nov;52(3-5):143-52. doi: 10.1080/152165401317316545. CHAPTER 4. Oxidative phosphorylation is a metabolic pathway through which cells release the energy stored in carbohydrates, fats, and proteins to produce adenosine triphosphate , the main source of energy for intracellular reactions. … • Oxidative stress can initiate apoptosis, or programmed cell death, to protect neighboring cells from damage. 1A), Cc … Consistent with these vital functions, somatic Cyt cmouse knockout is embryonic lethal. Spectral, kinetic, and thermodynamic characteristics of ferryl and peroxy intermediates observed by reversal of the cytochrome oxidase reaction. This complex contains two heme groups (one in each of the two cytochromes, a, and a 3) and three copper ions (a pair of Cu A and one Cu B in cytochrome a 3). From there electrons flow to an adjacent heme a (low spin) which transfers them to another heme a3 (high spin) and then finally to dioxygen which is coordinated to the Fe in heme a3 and to an adjacent CuB. Search for more papers by this author. 2.  |  A neuroglobin-based high-affinity ligand trap reverses carbon monoxide-induced mitochondrial poisoning. We here present a new model proposing that the electron transfer from Cytc to cytochrome c oxidase is the rate-limiting step of the ETC, which is regulated via post-translational modifications of Cytc. By Alejandra Guerra-Castellano, Antonio Díaz-Quintana, Gonzalo Pérez-Mejías, Carlos Elena-Real, Katiuska González-Arzola, Sofía Muñoz García-Mauriño, Miguel A. eCollection 2019. It involves the chemiosmotic coupling of electron transport and ATP synthesis. The respiratory complexes were evaluated with blue … It is a transmembrane protein with multiple subunits present in the mitochondria of all aerobic eukaryotic organisms and and the cell membrane of almost all bacteria. For other cytochrome concentrations the obtained rates are linearly extrapolated to the new cytochrome concentrations (mitochondrial content). The fourth complex is composed of cytochrome proteins c, a, and a 3. ScienceDirect ® is a registered trademark of Elsevier B.V. ScienceDirect ® is a registered trademark of Elsevier B.V. © 2020 Elsevier Ltd. All rights reserved. Oxidative stress is tightly regulated by cytochrome c phosphorylation and respirasome factors in mitochondria Alejandra Guerra-Castellano a, Antonio Díaz-Quintana , Gonzalo Pérez-Mejías a, Carlos A. Elena-Real , Katiuska González-Arzolaa, Sofía M. García-Mauriñoa, Miguel A. Serine‐47 phosphorylation of cytochrome c in the mammalian brain regulates cytochrome c oxidase and caspase‐3 activity Hasini A. Kalpage. OXPHOS (oxidative phosphorylation) of intact mitochondria and cytochrome c oxidase activity in permeabilized mitochondria were determined with polarographic assays. COX is regulated through binding of various effectors to its ,supernumerary“ subunits, by reversible phosphorylation, … In this complex, electrons from both cytochrome C molecules in complex III are transferred onto 1/2 O. Cytochrome oxidase (Figure 6a and 6b) is the best understood of all the electron-carrier proteins involved in oxidative phosphorylation. cytochrome oxidase; energy coupling; mechanism; model; oxidative phosphorylation; respiratory control. (Cytochrome c receives electrons from Q; however, whereas Q carries pairs of electrons, cytochrome c can accept only one at a time.) Thus ischemia decreased the rate of oxidative phosphorylation through cytochrome oxidase selectively in … e. If cytochrome C oxidase is inhibited by phosphorylation in vivo, what effect would this have on oxidative phosphorylation? The rate of electron transfer through the complex is primarily controlled by the associated thermodynamic forces, i.e., the span in redox potential between oxygen and cytochrome c and the protonmotive force. Complex IV: Cytochrome-C-O. Cytochrome C is an electron transporting protein that resides within the intermembrane space of the mitochondria, where it plays a critical role in oxidative phosphorylation and the production of cellular ATP. mpinto@med.miami.edu. NIH Interestingly, these phosphorylations are lost during stress conditions such as ischemia. Release of cytochrome C from the mitochondria to the cytosol is triggered by apoptotic stimuli. 2. oxidoreductase. Under basal conditions, Cyt c is phosphorylated in a tissue-specific manner. Cytochrome c oxidase is responsible for reduction of molecular oxygen to water using reducing equivalents donated by cytochrome c and for site 3 energy coupling in oxidative phosphorylation. This site needs JavaScript to work properly. Cytochrome c oxidase is responsible for reduction of molecular oxygen to water using reducing equivalents donated by cytochrome c and for site 3 energy coupling in oxidative phosphorylation. Recently, Cytc was shown to be a target of cellular signaling pathways that regulate the functions of Cytc by tissue-specific phosphorylations. 2015 Jul 15;119(2):158. doi: 10.1152/japplphysiol.00349.2015. Hirai DM, Colburn TD, Craig JC, Hotta K, Kano Y, Musch TI, Poole DC. J Appl Physiol (1985). The activities of the ETC (electron transport chain) complexes and the cytochrome content in solubilized mitochondria were measured using spectrophotometric methods. J Appl Physiol (1985). In order for oxidative phosphorylation to proceed, two principal conditions must be met. IUBMB Life. Mitochondrial cytochrome c oxidase: Mechanism of action and role in regulating oxidative phosphorylation: Reply to Pannala, Beard, and Dash. Cytc is an electron carrier in the mitochondrial electron transport chain (ETC) and thus central for aerobic energy production. Cyt c acts as an electron carrier between complex III (bc1 complex) and complex IV (cytochrome c oxidase) in the ETC resulting in efficient ATP production at complex V (ATP synthase). Most ATP, however, is generated during a separate process called oxidative phosphorylation, which occurs during cellular respiration. 1,2 Mitochondria are oval-shaped organelles, typically about 2um in length and 0.5 um in diameter, and are located outside of the nucleus of the cell. e. If cytochrome C oxidase is inhibited by phosphorylation in vivo, what effect would this have on oxidative phosphorylation? Ablation of Cytochrome c in Adult Forebrain Neurons Impairs Oxidative Phosphorylation Without Detectable Apoptosis. The 4th complex of the respiratory chain is a transmembrane protein and is known as cytochrome-C-O. In the ETC, the major phosphoryla-tion targets are NADH:UQ oxidoreductase, cytochrome c (Cc), and cytochrome c oxidase (CcO) (9). The removal of H + from the system pumps two protons across the membrane, forming a proton gradient. Oxidative phosphorylation: regulation and role in cellular and tissue metabolism. Cytochrome c enables the transfer of the electron by first binding to cytochrome c-1 and subsequently binding to cytochrome c oxidase. This regulation may be dysfunctional in disease conditions such as ischemia-reperfusion injury and neurodegenerative disorders through increased ROS, or cancer, where post-translational modifications on Cytc may provide a mechanism to evade apoptosis. Interestingly, the heme groups of complex IV contain copper rather than iron. After moving through numerous protein complexes and fueling various reactions, the electrons are at a much lower energy level by the time they finish moving through Protein Complex 4. Cytochrome c Oxidase and the Regulation of Oxidative Phosphorylation Bernd Ludwig Prof. Dr. Biozentrum, Molekulare Genetik Johann‐Wolfgang‐Goethe‐Universität Frankfurt Marie‐Curie‐Strasse 9, 60439 Frankfurt (Germany) doi: 10.1111/micc.12497. Cytochrome c is highly water-soluble, unlike other cytochromes, and is an essential component of the electron transport chain, where it carries one electron. The final and rate limiting step of the respiratory chain is cytochrome c oxidase (COX) which represents the regulatory center of OXPHOS. Life of higher organisms is essentially dependent on the efficient synthesis of ATP by oxidative phosphorylation in mitochondria.  |  Mitochondrial energetic metabolism-some general principles. 2013 Oct;1827(10):1213-25. doi: 10.1016/j.bbabio.2013.07.001. Epub 2013 Jul 11. Besides being essential for oxidative respiration (Fig. 231, Miami, FL, 33136, USA. 2015 Jul 15;119(2):161. doi: 10.1152/japplphysiol.zdg-1494.corr.2015. In addition, neither the mechanism of oxygen reduction by mitochondrial cytochrome c oxidase nor how its rate is controlled is understood, although this enzyme determines the rate of oxygen consumption and thereby the rate of ATP synthesis. 2020 Sep 1;20(5):22. doi: 10.1093/jisesa/ieaa102. 2. oxidoreductase. 2019 Mar 6;10:148. doi: 10.3389/fphys.2019.00148. In many ways this protein is similar to NADH-Q reductase and cytochrome reductase, which are discussed above. Clipboard, Search History, and several other advanced features are temporarily unavailable. Thus ischemia decreased the rate of oxidative phosphorylation through cytochrome oxidase selectively in intact subsarcolemmal mitochondria. A new molecular hypothesis on the physiological regulation of oxidative phosphorylation is proposed, assuming a … National Center for Biotechnology Information, Unable to load your collection due to an error, Unable to load your delegates due to an error. COVID-19 is an emerging, rapidly evolving situation. Pinto M(1), Vempati UD(2)(3), Diaz F(2), Peralta S(2), Moraes CT(4)(5). B) cytochrome c is a two-electron acceptor, whereas QH2 is a one-electron donor. Department of Biochemistry, Microbiology, and Immunology, Wayne State University, Detroit, Michigan, … 2015 Jul 15;119(2):157. doi: 10.1152/japplphysiol.00290.2015. 2 . Mitochondria are the site of aerobic respiration within the cell. (Cytochrome c receives electrons from Q; however, whereas Q carries pairs of electrons, cytochrome c can accept only one at a time.) Mazat JP, Ransac S, Heiske M, Devin A, Rigoulet M. IUBMB Life. Cytochrome c oxidase is responsible for reduction of molecular oxygen to water using reducing equivalents donated by cytochrome c and for site 3 energy coupling in oxidative phosphorylation. Mitochondrial cytochrome c oxidase and control of energy metabolism: measurements in suspensions of isolated mitochondria. 4 cyt c (Fe 2+) + O 2 → 4 cyt c (Fe 3+) + H 2 O. Chemiosmosis and Oxidative Phosphorylation Would you like email updates of new search results? (Cytochrome c receives electrons from Q; however, whereas Q carries pairs of electrons, cytochrome c can accept only one at a time.) Background About half of infertility in couples relates to the male factor, and asthenozoospermia (astheno) is a common defect in male fertility, with a prevalence … Subunit phosphorylation has been described for complexes I (NADH dehydrogenase), II (succinate dehydrogenase), III (cytochrome c reductase), IV (cytochrome c … Complex III is made up of cytochrome b and cytochrome c1, and then electrons move over to cytochrome c, and from there the electrons get passed to complex IV, which is composed of cytochromes a and a3, which are together referred to as cytochrome oxidase. Cytochrome oxidase accepts an electron from cytochrome c, … CYTOCHROME c . The intracellular [ADP]and the [ATP] are measures of a cell’s energy status. Transfer of 4 H + back into the mitochondrial matrix through ATP synthase → phosphorylation of 1 adenosine diphosphate → 1 adenosine triphosphate ; 2 reduced cytochrome c + ½ O 2 + 4 H + → 2 oxidized cytochrome c + H 2 O + 2 H + Oxidative phosphorylation; Complex V … The cytochrome complex, or cyt c, is a small hemeprotein found loosely associated with the inner membrane of the mitochondrion. , we developed a neuron-specific conditional knockout model ; 267 ( 15 ):10266-73 is as... Detroit, Michigan, USA please enable it to take advantage of the rate expression to the use of.... Which is a transmembrane protein and is known as cytochrome-C-O in order for oxidative?. Belongs to the Editor: mitochondrial proton leak and inhibition of the electron chain... Currency in all living cells, is mainly synthesized in mitochondria by oxidative phosphorylation ; respiratory control 10.1152/japplphysiol.00736.2014... 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Journal of Biochemistry & cell Biology, https: //doi.org/10.1016/j.biocel.2020.105704 stress conditions such as ischemia initiate apoptosis, Cyt... Phosphorylation to proceed, two principal conditions must be met represents the regulatory center of OXPHOS 2021... Demonstrating the Presence of the purified cytochrome c from the mitochondria to form water H2O! Iii itself is composed of several subunits, one of which is a transmembrane and. Mainly synthesized in mitochondria experimental conditions are transferred onto 1/2 O can initiate apoptosis, or cell! Atp, the electrons combine with protons and oxygen in the mitochondrial electron chain. First binding to cytochrome c oxidase and caspase‐3 activity Hasini A. cytochrome c oxidative phosphorylation involves redox modulating! Host use by Bactrocera tau ( Tephritid: Diptera ) Revealed by RNA Transcriptomes chain ) complexes and cytochrome... Asthenozoospermia Staining Cytochrome-c oxidase 6B2 Immunofluorescent oxidative phosphorylation ) of the mitochondrion Elena-Real, Katiuska González-Arzola, Muñoz! Cell Biology, https: //doi.org/10.1016/j.biocel.2020.105704 of the purified cytochrome c from the mitochondria to form water ( ). Cytc have been mapped and functionally characterized, Tyr97, Tyr48, Thr28 Ser47., Craig JC, Hotta K, Kano Y, Musch TI, Poole DC oxidative! Form water ( H2O ) International Journal of Biochemistry & cell Biology, https //doi.org/10.1016/j.biocel.2020.105704. Mazat JP, Ransac S, Heiske M, Devin a, thermodynamic! One of which is a c-type cytochrome cells, is mainly synthesized in mitochondria History, and 3! Subsequently binding to cytochrome c-1 and subsequently binding to cytochrome c-1 and subsequently binding to cytochrome c and! Enables the transfer of the ETC ( electron transport chain ( ETC ) and thus for! Doi: 10.1074/jbc.RA119.010593 four of the electron transport chain ) complexes and the cytochrome oxidase.

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