Editing Cytosol (section)

==Properties and composition==
[[File:Cellular Fluid Content.jpg|thumb|Intracellular fluid content in humans]]
The proportion of cell volume that is cytosol varies: for example while this compartment forms the bulk of cell structure in [[bacteria]],<ref name="Hoppert-1999"/> in plant cells the main compartment is the large central [[vacuole]].<ref>{{cite journal |vauthors=Bowsher CG, Tobin AK |title=Compartmentation of metabolism within mitochondria and plastids |journal=J. Exp. Bot. |volume=52 |issue=356 |pages=513–27 |date=April 2001 |pmid=11373301 |doi=10.1093/jexbot/52.356.513 |doi-access=free }}</ref> The cytosol consists mostly of water, dissolved ions, small molecules, and large water-soluble molecules (such as proteins). The majority of these non-protein molecules have a [[molecular mass]] of less than 300&nbsp;[[Atomic mass unit|Da]].<ref>{{cite journal |vauthors=Goodacre R, Vaidyanathan S, Dunn WB, Harrigan GG, Kell DB |title=Metabolomics by numbers: acquiring and understanding global metabolite data |journal=Trends Biotechnol. |volume=22 |issue=5 |pages=245–52 |date=May 2004 |pmid=15109811 |doi=10.1016/j.tibtech.2004.03.007 |url=http://personalpages.manchester.ac.uk/staff/roy.goodacre/learning/metabprof/Goodacre-TibTech2004.pdf |url-status=dead |archive-url=https://web.archive.org/web/20081217001301/http://personalpages.manchester.ac.uk/staff/roy.goodacre/learning/metabprof/Goodacre-TibTech2004.pdf |archive-date=2008-12-17 }}</ref> This mixture of small molecules is extraordinarily complex, as the variety of molecules that are involved in metabolism (the [[metabolite]]s) is immense. For example, up to 200,000 different small molecules might be made in plants, although not all these will be present in the same species, or in a single cell.<ref>{{cite journal |author=Weckwerth W |s2cid=1197884 |title=Metabolomics in systems biology |journal=[[Annu Rev Plant Biol]] |volume=54 |pages=669–89 |year=2003 |pmid=14503007 |doi=10.1146/annurev.arplant.54.031902.135014}}</ref> Estimates of the number of metabolites in single cells such as ''[[Escherichia coli|E. coli]]'' and [[Saccharomyces cerevisiae|baker's yeast]] predict that under 1,000 are made.<ref>{{cite journal |vauthors=Reed JL, Vo TD, Schilling CH, Palsson BO |title=An expanded genome-scale model of Escherichia coli K-12 (iJR904 GSM/GPR) |journal=Genome Biol. |volume=4 |issue=9 |pages=R54 |year=2003 |pmid=12952533 |pmc=193654 |doi=10.1186/gb-2003-4-9-r54 |doi-access=free }}</ref><ref>{{cite journal |vauthors=Förster J, Famili I, Fu P, Palsson BØ, Nielsen J |title=Genome-Scale Reconstruction of the Saccharomyces cerevisiae Metabolic Network |journal=Genome Res. |volume=13 |issue=2 |pages=244–53 |date=February 2003 |pmid=12566402 |pmc=420374 |doi=10.1101/gr.234503 }}</ref>

===Water===
Most of the cytosol is  [[water]], which makes up about 70% of the total volume of a typical cell.<ref name="Luby-Phelps-2000">{{cite journal |author=Luby-Phelps K |title=Cytoarchitecture and physical properties of cytoplasm: volume, viscosity, diffusion, intracellular surface area |journal=Int. Rev. Cytol. |volume=192 |pages=189–221 |year=2000 |pmid=10553280 |doi=10.1016/S0074-7696(08)60527-6 |url=http://webusers.physics.illinois.edu/~alek/598PNM/hw/IntRevCytol.pdf |series=International Review of Cytology |isbn=978-0-12-364596-8 |url-status=dead |archive-url=https://web.archive.org/web/20110719211202/http://webusers.physics.illinois.edu/~alek/598PNM/hw/IntRevCytol.pdf |archive-date=2011-07-19 }}</ref> The [[intracellular pH|pH]] of the intracellular fluid is 7.4.<ref>{{cite journal |vauthors=Roos A, Boron WF |title=Intracellular pH |journal=Physiol. Rev. |volume=61 |issue=2 |pages=296–434 |date=April 1981 |pmid=7012859 |doi=10.1152/physrev.1981.61.2.296 }}</ref> while mouse cell cytosolic [[pH]] ranges between 7.0 and 7.4, and is usually higher if a cell is growing.<ref>{{Cite journal| pmid = 3558476| volume = 104| issue = 4| pages = 1019–1033| last1 = Bright| first1 = G R| title = Fluorescence ratio imaging microscopy: temporal and spatial measurements of cytoplasmic pH| journal = The Journal of Cell Biology| year = 1987| doi = 10.1083/jcb.104.4.1019| last2 = Fisher| first2 = GW| last3 = Rogowska| first3 = J| last4 = Taylor| first4 = DL| pmc = 2114443}}</ref> The [[viscosity]] of cytoplasm is roughly the same as pure water, although [[diffusion]] of small molecules through this liquid is about fourfold slower than in pure water, due mostly to collisions with the large numbers of [[macromolecule]]s in the cytosol.<ref name="Verkman-2002">{{cite journal |author=Verkman AS |title=Solute and macromolecule diffusion in cellular aqueous compartments |journal=Trends Biochem. Sci. |volume=27 |issue=1 |pages=27–33 |date=January 2002 |pmid=11796221 |doi=10.1016/S0968-0004(01)02003-5}}</ref> Studies in the [[brine shrimp]] have examined how water affects cell functions; these saw that a 20% reduction in the amount of water in a cell inhibits metabolism, with metabolism decreasing progressively as the cell dries out and all metabolic activity halting when the water level reaches 70% below normal.<ref name="James-1984">{{cite journal |author=Clegg James S. |author-link = James S. Clegg|title=Properties and metabolism of the aqueous cytoplasm and its boundaries |journal=Am. J. Physiol. |volume=246 |issue=2 Pt 2 |pages=R133–51 |date=1984 |pmid=6364846 |doi=10.1152/ajpregu.1984.246.2.R133 | s2cid=30351411 |doi-access=}}</ref>

Although water is vital for life, the structure of this water in the cytosol is not well understood, mostly because methods such as [[nuclear magnetic resonance spectroscopy]] only give information on the average structure of water, and cannot measure local variations at the microscopic scale. Even the structure of pure water is poorly understood, due to the ability of water to form structures such as [[water cluster]]s through [[hydrogen bond]]s.<ref name="Wiggins-1990"/>

The classic view of water in cells is that about 5% of this water is strongly bound in by solutes or macromolecules as water of [[solvation]], while the majority has the same structure as pure water.<ref name="James-1984"/> This water of solvation is not active in [[osmosis]] and may have different solvent properties, so that some dissolved molecules are excluded, while others become concentrated.<ref>{{cite journal |author=Fulton AB |title=How crowded is the cytoplasm? |journal=Cell |volume=30 |issue=2 |pages=345–7 |date=September 1982 |pmid=6754085 |doi=10.1016/0092-8674(82)90231-8|s2cid=6370250 }}</ref><ref>{{cite journal |author=Garlid KD |title=The state of water in biological systems |journal=Int. Rev. Cytol. |volume=192 |pages=281–302 |year=2000 |pmid=10553283 |doi=10.1016/S0074-7696(08)60530-6 |series=International Review of Cytology |isbn=978-0-12-364596-8}}</ref> However, others argue that the effects of the high concentrations of macromolecules in cells extend throughout the cytosol and that water in cells behaves very differently from the water in dilute solutions.<ref>{{cite journal |author=Chaplin M |title=Do we underestimate the importance of water in cell biology? |journal=Nat. Rev. Mol. Cell Biol. |volume=7 |issue=11 |pages=861–6 |date=November 2006 |pmid=16955076 |doi=10.1038/nrm2021|s2cid=42919563 }}</ref> These ideas include the proposal that cells contain zones of low and high-density water, which could have widespread effects on the structures and functions of the other parts of the cell.<ref name="Wiggins-1990">{{cite journal|author=Wiggins PM|author-link=Philippa Wiggins|date=1 December 1990|title=Role of water in some biological processes|journal=Microbiol. Rev.|volume=54|issue=4|pages=432–49|doi=10.1128/MMBR.54.4.432-449.1990|pmc=372788|pmid=2087221}}</ref><ref>{{cite journal|author=Wiggins PM|author-link=Philippa Wiggins|date=June 1996|title=High and low density water and resting, active and transformed cells|journal=Cell Biol. Int.|volume=20|issue=6|pages=429–35|doi=10.1006/cbir.1996.0054|pmid=8963257|s2cid=42866068}}</ref> However, the use of advanced nuclear magnetic resonance methods to directly measure the mobility of water in living cells contradicts this idea, as it suggests that 85% of cell water acts like that pure water, while the remainder is less mobile and probably bound to macromolecules.<ref>{{cite journal |vauthors=Persson E, Halle B |title=Cell water dynamics on multiple time scales |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=105 |issue=17 |pages=6266–71 |date=April 2008 |pmid=18436650 |pmc=2359779 |doi=10.1073/pnas.0709585105|bibcode=2008PNAS..105.6266P |doi-access=free }}</ref>

===Ions===
The concentrations of the other [[ion]]s in cytosol are quite different from those in [[extracellular fluid]] and the cytosol also contains much higher amounts of charged macromolecules such as proteins and nucleic acids than the outside of the cell structure.

{| class="wikitable" style="margin:auto; text-align:center;"
|+ Typical ion concentrations in mammalian cytosol and plasma.<ref name="Lodish-1999">{{cite book |author=Lodish, Harvey F. |title=Molecular cell biology |publisher=Scientific American Books |location=New York |year=1999 |isbn=0-7167-3136-3 |oclc=174431482 |url-access=registration |url=https://archive.org/details/molecularcellbio00lodi }}</ref>
|-
! rowspan=2 | Ion
! colspan=2 | [[Molar concentration|Concentration]] (millimolar)
|-
! In cytosol 
! In plasma
|-
| [[Potassium]]
| 139–150<ref>{{Cite journal|title=Potassium physiology|first=S. O.|last=Thier|date=April 25, 1986|journal=The American Journal of Medicine|volume=80|issue=4A|pages=3–7|doi=10.1016/0002-9343(86)90334-7|pmid=3706350}}</ref><ref name="Lote-2012">{{cite book |last=Lote |first=Christopher J. |title= Principles of Renal Physiology, 5th edition|page=12|year=2012|publisher=Springer}}</ref>
| 4
|-
| [[Sodium]]
| 12
| 145
|-
| [[Chloride]]
| 4
| 116
|-
| [[Bicarbonate]]
| 12
| 29
|-
| [[Amino acid]]s in proteins
| 138
| 9
|-
| [[Magnesium]]
| 0.8
| 1.5
|-
| [[Calcium]]
| <0.0002
| 1.8
|}

In contrast to extracellular fluid, cytosol has a high concentration of [[potassium]] ions and a low concentration of [[sodium]] ions.<ref name="Lang-2007">{{cite journal |author=Lang F |title=Mechanisms and significance of cell volume regulation |journal=J Am Coll Nutr |volume=26 |issue=5 Suppl |pages=613S–623S |date=October 2007 |pmid=17921474 |doi=10.1080/07315724.2007.10719667 |s2cid=1798009 }}</ref> This difference in ion concentrations is critical for [[osmoregulation]], since if the ion levels were the same inside a cell as outside, water would enter constantly by [[osmosis]] - since the levels of [[macromolecule]]s inside cells are higher than their levels outside. Instead, sodium ions are expelled and potassium ions taken up by the [[Na⁺/K⁺-ATPase]], potassium ions then flow down their concentration gradient through potassium-selection ion channels, this loss of positive charge creates a negative [[membrane potential]]. To balance this [[potential difference]], negative chloride ions also exit the cell, through selective chloride channels. The loss of sodium and chloride ions compensates for the osmotic effect of the higher concentration of organic molecules inside the cell.<ref name="Lang-2007"/>

Cells can deal with even larger osmotic changes by accumulating [[osmoprotectant]]s such as [[betaines]] or [[trehalose]] in their cytosol.<ref name="Lang-2007"/> Some of these molecules can allow cells to survive being completely dried out and allow an organism to enter a state of suspended animation called [[cryptobiosis]].<ref>{{cite journal |vauthors=Sussich F, Skopec C, Brady J, Cesàro A |title=Reversible dehydration of trehalose and anhydrobiosis: from solution state to an exotic crystal? |journal=Carbohydr. Res. |volume=334 |issue=3 |pages=165–76 |date=August 2001 |pmid=11513823 |doi=10.1016/S0008-6215(01)00189-6}}</ref> In this state the cytosol and osmoprotectants become a glass-like solid that helps stabilize proteins and cell membranes from the damaging effects of desiccation.<ref>{{cite journal |vauthors=Crowe JH, Carpenter JF, Crowe LM |title=The role of vitrification in anhydrobiosis |journal=[[Annu. Rev. Physiol.]] |volume=60 |pages=73–103 |year=1998 |pmid=9558455 |doi=10.1146/annurev.physiol.60.1.73}}</ref>

The low concentration of [[calcium]] in the cytosol allows calcium ions to function as a [[second messenger]] in [[calcium signaling]]. Here, a signal such as a [[hormone]] or an [[action potential]] opens [[calcium channel]] so that calcium floods into the cytosol.<ref>{{cite journal |author=Berridge MJ |title=Elementary and global aspects of calcium signalling |journal=J. Physiol. |volume=499 |issue= Pt 2|pages=291–306 |date=1 March 1997|pmid=9080360 |pmc=1159305 |doi=10.1113/jphysiol.1997.sp021927 |url=http://www.jphysiol.org/cgi/pmidlookup?view=long&pmid=9080360 }}</ref> This sudden increase in cytosolic calcium activates other signalling molecules, such as [[calmodulin]] and [[protein kinase C]].<ref>{{cite journal |vauthors=Kikkawa U, Kishimoto A, Nishizuka Y |title=The protein kinase C family: heterogeneity and its implications |journal=[[Annu. Rev. Biochem.]] |volume=58 |pages=31–44 |year=1989 |pmid=2549852 |doi=10.1146/annurev.bi.58.070189.000335}}</ref> Other ions such as chloride and potassium may also have signaling functions in the cytosol, but these are not well understood.<ref>{{cite journal |vauthors=Orlov SN, Hamet P |title=Intracellular monovalent ions as second messengers |journal=J. Membr. Biol. |volume=210 |issue=3 |pages=161–72 |date=April 2006 |pmid=16909338 |doi=10.1007/s00232-006-0857-9|s2cid=26068558 }}</ref>

===Macromolecules===
Protein molecules that do not bind to [[cell membrane]]s or the [[cytoskeleton]] are dissolved in the cytosol. The amount of protein in cells is extremely high, and approaches 200&nbsp;mg/ml, occupying about 20–30% of the volume of the cytosol.<ref name="Ellis-2001">{{cite journal |author=Ellis RJ |title=Macromolecular crowding: obvious but underappreciated |journal=Trends Biochem. Sci. |volume=26 |issue=10 |pages=597–604 |date=October 2001 |pmid=11590012 |doi=10.1016/S0968-0004(01)01938-7}}</ref> However, measuring precisely how much protein is dissolved in cytosol in intact cells is difficult, since some proteins appear to be weakly associated with membranes or organelles in whole cells and are released into solution upon [[cell lysis]].<ref name="James-1984"/> Indeed, in experiments where the plasma membrane of cells were carefully disrupted using [[saponin]], without damaging the other cell membranes, only about one quarter of cell protein was released. These cells were also able to synthesize proteins if given ATP and amino acids, implying that many of the enzymes in cytosol are bound to the cytoskeleton.<ref>{{cite journal |vauthors=Hudder A, Nathanson L, Deutscher MP |title=Organization of Mammalian Cytoplasm |journal=Mol. Cell. Biol. |volume=23 |issue=24 |pages=9318–26 |date=December 2003 |pmid=14645541 |pmc=309675 |doi=10.1128/MCB.23.24.9318-9326.2003}}</ref> However, the idea that the majority of the proteins in cells are tightly bound in a network called the [[microtrabecular lattice]] is now seen as unlikely.<ref>{{cite journal |author=Heuser J |title=Whatever happened to the 'microtrabecular concept'? |journal=Biol Cell |year=2002 |volume=94 |issue=9| pages=561–96  |doi=10.1016/S0248-4900(02)00013-8 |pmid=12732437|s2cid=45792524 }}</ref>

In prokaryotes the cytosol contains the cell's [[genome]], within a structure known as a [[nucleoid]].<ref>{{cite journal |vauthors=Thanbichler M, Wang S, Shapiro L |title=The bacterial nucleoid: a highly organized and dynamic structure |journal=J Cell Biochem |volume=96 |issue=3 |pages=506–21 |year=2005 |pmid=15988757 |doi=10.1002/jcb.20519|s2cid=25355087 |doi-access=free }}</ref> This is an irregular mass of [[DNA]] and associated proteins that control the [[transcription (genetics)|transcription]] and [[DNA replication|replication]] of the bacterial [[chromosome]] and [[plasmid]]s. In eukaryotes the genome is held within the [[cell nucleus]], which is separated from the cytosol by [[nuclear pore]]s that block the free diffusion of any molecule larger than about 10&nbsp;[[nanometre]]s in diameter.<ref>{{cite book |author=Peters R |chapter=Introduction to Nucleocytoplasmic Transport |title=Xenopus Protocols |volume=322 |pages=235–58 |year=2006 |pmid=16739728 |doi=10.1007/978-1-59745-000-3_17 |series=Methods in Molecular Biology |isbn=978-1-58829-362-6}}</ref>

This high concentration of macromolecules in cytosol causes an effect called [[macromolecular crowding]], which is when the [[activity (chemistry)|effective concentration]] of other macromolecules is increased, since they have less volume to move in. This crowding effect can produce large changes in both the [[reaction rate|rates]] and the position of [[chemical equilibrium]] of reactions in the cytosol.<ref name="Ellis-2001"/> It is particularly important in its ability to alter [[dissociation constant]]s by favoring the association of macromolecules, such as when multiple proteins come together to form [[protein complex]]es, or when [[DNA-binding protein]]s bind to their targets in the [[genome]].<ref>{{cite journal |vauthors=Zhou HX, Rivas G, Minton AP |title=Macromolecular crowding and confinement: biochemical, biophysical, and potential physiological consequences |journal=[[Annu Rev Biophys]] |volume=37 |pages=375–97 |year=2008 |pmid=18573087 |doi=10.1146/annurev.biophys.37.032807.125817 |pmc=2826134}}</ref>