Magnesium in biology 378938 222534897 2008-06-29T21:29:55Z DOI bot 6652755 Citation maintenance. Formatted: pages, doi, pmid, title. You can [[WP:DOI|use this bot]] yourself! Please [[User:DOI_bot/bugs|report any bugs]]. '''Magnesium''' is an essential element '''in biological systems'''. [[Magnesium]] occurs typically as the Mg<sup>2+</sup> ion. It is an essential mineral [[nutrient]] for life<ref name="Leroy 1926">{{cite journal| last=Leroy| first=J.| year=1926| title=Necessite du magnesium pour la croissance de la souris| journal=Comptes Rendus de Seances de la Societe de Biologie| volume=94| pages= 431–433}}</ref><ref name="Lusk 1968">{{cite journal| last=Lusk| first=J.E.| coauthors=Williams, R.J.P., and Kennedy, E.P.| year=1968| title=Magnesium and the growth of Escherichia coli| journal=Journal of Biological Chemistry| volume=243| pages=2618–2624}}</ref><ref name="Marschner 1995">{{cite book| last=Marschner| first= H.| year=1995| title=Mineral Nutrition in Higher Plants| location=San Diego| publisher= Academic Press}}</ref> and is present in every [[cell (biology)|cell]] type in every organism. ==Function== A balance of magnesium is vital to the well being of all organisms. Magnesium is a relatively abundant ion in the [[lithosphere]] and is highly bioavailable in the [[hydrosphere]]. This ready availability, in combination with a useful and very unusual chemistry, may have led to its usefulness in evolution as an ion for signalling, enzyme activation and [[catalysis]]. However, the unusual nature of ionic magnesium has also led to a major challenge in the use of the ion in biological systems. Biological membranes are impermeable to Mg<sup>2+</sup> (and other ions) so transport proteins must facilitate the flow of Mg<sup>2+</sup>, both into and out of cells and intracellular compartments. ==Biological range, distribution, and regulation== In [[animal]]s it has been shown that different cell types maintain different concentrations of magnesium.<ref name="Valberg 1965">{{cite journal| last=Valberg| first= L.S.| coauthors=Holt, J.M., Paulson, E., and Szivek, J.| year=1965| title=Spectrochemical analysis of sodium, potassium, calcium, magnesium, copper, and zinc in normal human erythrocytes| journal=Journal of Clinical Investigation| volume=44| pages= 379–389| doi=10.1172/JCI105151}}</ref><ref name="Seiler 1966">{{cite journal| last=Seiler| first=R.H.| coauthors=Ramirez, O., Brest, A.N., and Moyer, J.H.| year=1966| title=Serum and erythrocytic magnesium levels in congestive heart failure: effect of hydrochlorothiazide| journal=American Journal of Cardiology| volume= 17| pages= 786–791| doi=10.1016/0002-9149(66)90372-9}}</ref><ref name="Walser 1967">{{cite journal| last=Walser| first=M.| year=1967| title=Magnesium metabolism| journal=Ergebnisse der Physiologie Biologischen Chemie und Experimentellen Pharmakologie| volume=59| pages=185–296| doi=10.1007/BF02269144}}</ref><ref name="Iyengar 1978">{{cite book| last=Iyengar| first=G.V.| coauthors= Kollmer, W.E., and Bowen, H.J.M.| year=1978| title=The Elemental Composition of Human Tissues and Body Fluids| location=Weinheim, New York| publisher=Verlag Chemie}}</ref> It seems likely that the same is true for [[plants]].<ref name="Stelzer 1990">{{cite journal| last=Stelzer| first=R.| coauthors=Lehmann, H., Krammer, D., and Luttge, U.| year=1990| title=X-Ray microprobe analysis of vacuoles of spruce needle mesophyll, endodermis and transfusion parenchyma cells at different seasons of the year| journal=Botanica Acta| volume=103| pages=415–423}}</ref><ref name="Shaul 1999">{{cite journal| last=Shaul| first=O.| coauthors=Hilgemann, D.W., de-Almeida-Engler, J., Van, M.M., Inze, D., and Galili, G.| year=1999| title=Cloning and characterization of a novel Mg<sup>2+</sup>/H<sup>+</sup> exchanger| journal=EMBO Journal| volume=18| pages=3973–3980| doi=10.1093/emboj/18.14.3973}}</ref> This suggests that different cell types may regulate influx and efflux of magnesium in different ways based on their unique metabolic needs. Interstitial and systemic concentrations of free magnesium must be delicately maintained by the combined processes of buffering (binding of ions to proteins and other molecules) and muffling (the transport of ions to storage or extracellular spaces<ref name="Thomas 1991">{{cite journal| last=Thomas| first= R.C.| coauthors= Coles, J.A., and Deitmer, J.W. | year=1991| title= Homeostatic muffling| journal= Nature| volume= 350| pages= 564| doi=10.1038/350564b0}}</ref>). In plants, and more recently in animals, magnesium has been recognized as an important signaling ion, both activating and mediating many biochemical reactions. The best example of this is perhaps the regulation of [[carbon]] fixation in [[chloroplast]]s in the [[Calvin cycle]].<ref name="Berkowitz 1993">{{cite journal| last=Berkowitz| first= G.A.| coauthors= Wu, W.| year= 1993| title= Magnesium, potassium flux and photosynthesis| journal=Magnesium Research| volume= 6| pages= 257–265}}</ref><ref name="Shaul 2002">{{cite journal| last=Shaul| first= O. | year=2002| title= Magnesium transport and function in plants: the tip of the iceberg| journal=BioMetals| volume= 15| pages= 309–323| doi=10.1023/A:1016091118585}}</ref> The importance of magnesium to proper cellular function cannot be understated. Deficiency of the [[nutrient]] results in disease in the affected organism. In single-celled organisms such as [[bacteria]] and [[yeast]], low levels of magnesium manifests in greatly reduced growth rates. In magnesium transport [[knockout]] strains of bacteria, healthy rates are maintained only with exposure to very high external concentrations of the ion.<ref name="Hmiel 1989">{{cite journal| last=Hmiel| first= S.P.| coauthors= Snavely, M.D., Florer, J.B., Maguire, M.E., and Miller, C.G. | year=1989| title= Magnesium transport in Salmonella typhimurium: genetic characterization and cloning of three magnesium transport loci| journal= Journal of Bacteriology| volume= 171| pages= 4742–4751}}</ref><ref name="MacDiarmid 1998">{{cite journal| last=MacDiarmid| first= C.W.| coauthors= Gardner, R.C. | year=1998| title= Overexpression of the Saccharomyces cerevisiae magnesium transport system confers resistance to aluminum ion| journal= J. Biol. Chem.| volume= 273| pages= 1727–1732| doi=10.1074/jbc.273.3.1727| pmid=9430719}}</ref> In yeast, [[mitochondria]]l magnesium deficiency is also leads to disease.<ref name="Wiesenberger 1992">{{cite journal| last=Wiesenberger| first= G.| coauthors= Waldherr, M., and Schweyen, R.J. | year=1992| title= The nuclear gene MRS2 is essential for the excision of group II introns from yeast mitochondrial transcripts ''in vivo''| journal= J. Biol. Chem.| volume= 267| pages= 6963–6969}}</ref> Plants deficient in Magnesium show stress responses. The first observable signs of both magnesium starvation and overexposure in plants is a decrease in the rate of [[photosynthesis]]. This is due to the central position of the Mg<sup>++</sup> ion in the [[chlorophyll]] molecule. The later effects of magnesium deficiency on plants are a significant reduction in growth and reproductive viability.<ref name="Marschner 1995"/> Magnesium can also be toxic to plants, although this is typically seen only in [[drought]] conditions.<ref name="Kaiser 1987">{{cite journal| last=Kaiser| first= W.M. | year=1987| title= Effects of water deficit on photosynthetic capacity| journal= Physiologia Plantarum| volume= 71| pages= 142–149| doi=10.1111/j.1399-3054.1987.tb04631.x}}</ref><ref name="Rao 1987">{{cite journal| last=Rao| first= I.M.| coauthors= Sharp, R.E., and Boyer, J.S. | year=1987| title= Leaf magnesium alters photosynthetic response to low water potentials in sunflower| journal= Plant Physiology| volume= 92| pages= 29–36}}</ref> [[Image:Chlorophyll-a-3D-vdW.png|thumb|Space-filling model of the chlorophyll a molecule, with the Magnesium ion (bright green) visible at the center of the [[porphyrin]] group]] In animals, magnesium deficiency ([[hypomagnesemia]]) is seen when the environmental availability of magnesium is low. In ruminant animals, particularly vulnerable to magnesium availability in pasture grasses, the condition is known as ‘grass tetany’. Hypomagnesemia is identified by a loss of balance due to muscle weakness.<ref name="Grunes 1970">{{cite journal| last=Grunes| first= D.L.| coauthors= Stout, P.R., and Brownwell, J.R. | year= 1970| title= Grass tetany of ruminants| journal= Advances in Agronomy| volume= 22| pages= 332–374}}</ref> A number of genetically attributable hypomagnesemia disorders have also been identified in humans.<ref name="Paunier 1968">{{cite journal| last=Paunier| first= L.| coauthors= Radde, I.C., Kooh, S.W., Conen, P.E., and Fraser, D. | year=1968| title= Primary hypomagnesemia with secondary hypocalcemia in an infant| journal= Pediatrics| volume= 41| pages= 385–402}}</ref><ref name="Weber 2000">{{cite journal| last=Weber| first= S.| coauthors= Hoffmann, K., Jeck, N., Saar, K., Boeswald, M., Kuwertz-Broeking, E., Meij, I.I.C., Knoers, N.V.A.M., Cochat, P., Sulakova, T., Bonzel, K.E., Soergel, M., Manz, F., Schaerer, K., Seyberth, H.W., Reis, A., and Konrad, M. | year=2000| title= Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis maps to chromosome 3q27 and is associated with mutations in the PCLN-1 gene| journal= European Journal of Human Genetics| volume= 8| pages= 414–422| doi=10.1038/sj.ejhg.5200475}}</ref><ref name="Weber 2001">{{cite journal| last=Weber| first= S.| coauthors= Schneider, L., Peters, M., Misselwitz, J., Roennefarth, G., Boeswald, M., Bonzel, K.E., Seeman, T., Sulakova, T., Kuwertz-Broeking, E., Gregoric, A., Palcoux, J.-B., Tasic, V., Manz, F., Schaerer, K., Seyberth, H.W., and Konrad, M. | year=2001| title= Novel paracellin-1 mutations in 25 families with familial hypomagnesemia with hypercalciuria and nephrocalcinosis| journal= Journal of the American Society of Nephrology| volume= 12| pages= 1872–1881}}</ref><ref name="Chubanov 2004">{{cite journal| last=Chubanov| first= V.| coauthors= Waldegger, S., Mederos y Schnitzler, M., Vitzthum, H., Sassen, M.C., Seyberth, H.W., Konrad, M., and Gudermann, T. | year= 2004| title= Disruption of TRPM6/TRPM7 complex formation by a mutation in the TRPM6 gene causes hypomagnesemia with secondary hypocalcemia| journal= Proceedings of the National Academy of Sciences of the United States of America| volume= 101| pages= 2894–2899| doi=10.1073/pnas.0305252101| pmid=14976260}}</ref> Overexposure to magnesium, may be toxic to individual cells, though these effects have been difficult to show experimentally. In humans the condition is termed hypermagnesemia, and is well documented, though it is usually caused by loss of [[kidney]] function. In healthy individuals, excess magnesium is rapidly excreted in the urine (Harrison’s Principles of Internal Medicine, Online Edition). === Human health === {{main|Magnesium deficiency (medicine)}} Magnesium deficiency in humans was first described in the medical literature in 1934. The adult human daily nutritional requirement, which is affected by various factors including gender, weight and size, is 300-400 [[milligram|mg]]/day. Inadequate magnesium intake frequently causes muscle [[spasm]]s, and has been associated with [[cardiovascular disease]], [[diabetes]], [[high blood pressure]], [[anxiety]] disorders, [[migraine]]s, [[osteoporosis]] and [[cerebral infarction]]<ref name="pmid18332289">{{cite journal |author=Larsson SC, Virtanen MJ, Mars M, ''et al'' |title=Magnesium, calcium, potassium, and sodium intakes and risk of stroke in male smokers |journal=Arch. Intern. Med. |volume=168 |issue=5 |pages=459–65 |year=2008 |month=March |pmid=18332289 |doi=10.1001/archinte.168.5.459 |url=}}</ref>. Acute deficiency (see [[hypomagnesemia]]) is rare, and is more common as a drug side effect (such as chronic alcohol or diuretic use) than from low food intake per se, but it can also occur within people fed intravenously for extended periods of time. The incidence of chronic deficiency resulting in less than optimal health is debated. The [[Dietary Reference Intake|DRI]] upper tolerated limit for [[Dietary supplement|supplemental]] magnesium is 350 mg/day (calculated as mg of Mg elemental in the salt). (Supplements based on Amino Acid Chelates, Glycinate, Lysinate etc. are much better tolerated by the digestive system and do not have the side effects of the older compounds used.){{Fact|date=November 2007}} The most common symptom of excess oral magnesium intake is [[diarrhea]]. Since the kidneys of adult humans excrete excess magnesium efficiently, oral magnesium poisoning in adults with normal renal function is very rare. Infants, which have less ability to excrete excess magnesium even when healthy, should not be given magnesium supplements, except under a physician's care. Magnesium salts (usually in the form of magnesium sulfate or chloride when given [[parenterally]]) are used therapeutically for a number of medical conditions, see [[Epsom salts]] for a list of conditions which have been treated with supplemental magnesium ion. Magnesium is absorbed with reasonable efficiency (30% to 40%) by the body from any soluble magnesium salt, such as the chloride or citrate. Magnesium is similarly absorbed from [[Epsom salts]], although the sulfate in these salts adds to their laxative effect at higher doses. Magnesium absorption from the insoluble oxide and hydroxide salts ([[milk of magnesia]]) is erratic and of poorer efficiency, since it depends on the neutralization and solution of the salt by the acid of the stomach, which may not be (and usually is not) complete. [[Magnesium orotate]] may be used as adjuvant therapy in patients on optimal treatment for severe [[congestive heart failure]], increasing survival rate and improving clinical symptoms and patient's quality of life.<ref name="pmid18281113">{{cite journal |author=Stepura OB, Martynow AI |title=Magnesium orotate in severe congestive heart failure (MACH) |journal=Int. J. Cardiol. |volume= |issue= |pages= |year=2008 |month=February |pmid=18281113 |doi=10.1016/j.ijcard.2007.11.022 |url=}}</ref> ====Autism==== According to a recent online survey, approximately 30% of parents give their autistic children a supplement of magnesium and [[vitamin B6]] (Green 2006). There are conflicting studies as to whether or not this is an effective therapy for autism (Martineau 1985, Tolbert 1993, Findling 1997, Lelord 1981). There is no standardization of what dosages of magnesium and vitamin B6, nor are there standards as to which preparations of magnesium should be used. Varying doses used in popular practice may be confounding the results of scientific studies. Magnesium supplementation aims to normalize low levels in tissues, thus appropriate assays, such as erythrocyte magnesium measurements, should be used in dose ranging studies. Mousain-Bosc and colleagues (2006) showed that children with autism - pervasive developmental disorder (PDD) (''n'' = 33) had significantly lower red blood cell magnesium levels than controls (''n'' = 36). Intervention with magnesium and vitamin B6 (pyridoxine) reduced PDD symptoms in 23 children out of 33, stereotyped restricted behavior (18 children), and abnormal/delayed functioning (17 children); it improved social interactions in 23 children and communication in 24 children. ====Attention deficit hyperactivity disorder==== Mousain-Bosc and colleagues (2006) showed that children with [[attention deficit hyperactivity disorder]] (ADHD) (''n'' = 46) had significantly lower red blood cell magnesium levels than controls (''n'' = 30). Intervention with magnesium and vitamin B6 (pyridoxine) reduced hyperactivity, hyperemotivity/aggressiveness and improved school attention. ==== Nerve Conduction ==== Magnesium can effect muscle relaxation through direct action on the cell membrane. Mg<sup>++</sup> ions close certain types of calcium channels, which conduct a positive charge into the [[neuron]]. With an excess of magnesium, more channels will be blocked and the nerve will have less activity.{{Fact|date=April 2008}} ====Hypertension==== Magnesium-containing [[Epsom salts]] are especially used the hypertension of [[eclampsia]]. Even if the case is not eclampsia, there may be [[antihypertensive]] effects of having a substantial portion of the intake of [[sodium chloride]] (NaCl) exchanged for e.g. magnesium chloride; NaCl is an [[osmolite]] and increases [[arginine vasopressin]] (AVP) release, which increases [[extracellular volume]] and thus results in increased blood pressure. However, not all osmolites have this effect on AVP release<ref name=boron871> {{cite book |author=Walter F., PhD. Boron |title=Medical Physiology: A Cellular And Molecular Approaoch |publisher=Elsevier/Saunders |location= |year= |pages= |isbn=1-4160-2328-3 |oclc= |doi=}} Page 871</ref>, so with magnesium chloride, the increase in osmolarity may not cause such a hypertensive response. === Food sources === [[Image:FoodSourcesOfMagnesium.jpg|upright|thumb|Some good sources of magnesium.]] [[Green vegetable]]s such as [[spinach]] provide magnesium because of the abundance of [[chlorophyll]] molecules which contain the ion. [[nut (fruit)|Nut]]s (especially [[cashew]]s and [[almond]]s), [[seed]]s, and some [[whole grain]]s are also good sources of magnesium. Although many foods contain magnesium, it is usually found in low levels. As with most nutrients, daily needs for magnesium are unlikely to be met by one serving of any single food. Eating a wide variety of fruits, vegetables, and grains will help ensure adequate intake of magnesium. Because magnesium readily dissolves in water, refined foods, which are often processed or cooked in water and dried, are generally poor sources of the nutrient. For example, whole-wheat bread has twice as much magnesium as white bread because the magnesium-rich germ and bran are removed when white flour is processed. The table of food sources of magnesium suggests many dietary sources of magnesium. [[Hard water|"Hard" water]] can also provide magnesium, but [[Soft water|"soft" water]] does not contain the ion. Dietary surveys do not asses magnesium intake from water, which may lead to underestimating total magnesium intake and its variability. Too much magnesium may make it difficult for the body to absorb [[calcium]]. Not enough magnesium can lead to [[hypomagnesemia]] as described above, with irregular heartbeats, high blood pressure (a sign in humans but not some experimental animals such as rodents), insomnia and muscle spasms ([[fasciculation]]). However, as noted, symptoms of low magnesium from pure dietary deficiency are thought to be rarely encountered. Following are some foods and the amount of magnesium in them: * spinach (1/2 cup) = 80 milligrams (mg) * peanut butter (2 tablespoons) = 50 mg * black-eyed peas (1/2 cup) = 45 mg * milk: low fat (1 cup) = 40 mg The U.S. [[Recommended Dietary Allowance|RDA/RDV]] is 400 mg of magnesium. ==Biological chemistry== Mg<sup>2+</sup> is the fourth most abundant [[metal]] [[ion]] in cells (in moles) and the most abundant free divalent cation — as a result it is deeply and intrinsically woven into cellular [[metabolism]]. Indeed, Mg<sup>2+</sup>-dependent enzymes appear in virtually every metabolic pathway: specific binding of Mg<sup>2+</sup> to biological membranes is frequently observed, Mg<sup>2+</sup> is also used as a signalling molecule, and much of nucleic acid biochemistry requires Mg<sup>2+</sup>, including all reactions which require release of energy from ATP.<ref name="Cowan 1995">{{cite book| last=Cowan| first= J.A. | year= 1995| title= Introduction to the biological chemistry of magnesium| work=The Biological Chemistry of Magnesium| editor=J.A. Cowan | location=New York| publisher=VCH}}</ref><ref name="Romani 2002">{{cite journal| last=Romani| first= A.M.P.| coauthors= Maguire, M.E. | year=2002| title= Hormonal regulation of Mg<sup>2+</sup> transport and homeostasis in eukaryotic cells| journal=BioMetals| volume= 15| pages= 271–283| doi=10.1023/A:1016082900838}}</ref><ref name="Shaul 2002"/> In nucleotides, the triple phosphate moiety of the compound is invariably stabilized by association with Mg<sup>2+</sup> in all enzymic processes. ===Chlorophyll=== In photosynthetic organisms Mg<sup>2+</sup> has the additional vital role of being the coordinating ion in the chlorophyll molecule. This role was discovered by R. M. Willstätter, who received the Nobel Prize in Chemistry 1915 for the purification and structure of chlorophyll. ===Enzymes=== The chemistry of the Mg<sup>2+</sup> ion, as applied to enzymes, uses the full range of this ion’s unusual reaction chemistry to fulfill a range of functions.<ref name="Black 1995a">{{cite journal| last=Black| first= C.B.| coauthors=Cowan, J.A.| year= 1995| title= Magnesium-dependent enzymes in nucleic acid biochemistry| work=The Biological Chemistry of Magnesium| editor=J.A. Cowan | location=New York| publisher=VCH}}</ref><ref name="Black 1995b">{{cite journal| last=Black| first= C.B.| coauthors= Cowan, J.A. | year=1995| title= Magnesium-dependent enzymes in general metabolism| work=The Biological Chemistry of Magnesium| editor=J.A. Cowan | location=New York| publisher=VCH}}</ref><ref name="Cowan 1995"/><ref name="Cowan 2002">{{cite journal| last=Cowan| first= J.A. | year= 2002| title= Structural and catalytic chemistry of magnesium-dependent enzymes| journal=BioMetals| volume=15 | pages= 225–235| doi=10.1023/A:1016022730880}}</ref> Mg<sup>2+</sup> interacts with substrates, enzymes and occasionally both (Mg<sup>2+</sup> may form part of the active site). Mg<sup>2+</sup> generally interacts with substrates through inner sphere coordination, stabilising anions or reactive intermediates, also including binding to ATP and activating the molecule to nucleophilic attack. When interacting with enzymes and other proteins Mg<sup>2+</sup> may bind using inner or outer sphere coordination, to either alter the conformation of the enzyme or take part in the chemistry of the catalytic reaction. In either case, because Mg<sup>2+</sup> is only rarely fully dehydrated during ligand binding, it may be a water molecule associated with the Mg<sup>2+</sup> that is important rather than the ion itself. The Lewis acidity of Mg<sup>2+</sup> ([[Acid dissociation constant|p''K''<sub>a</sub>]] 11.4) is used to allow both hydrolysis and condensation reactions (most commonly phosphate ester hydrolysis and phosphoryl transfer) that would otherwise require pH values greatly removed from physiological values. === Essential role in the biological activity of ATP === [[Adenosine triphosphate|ATP]] (adenosine triphosphate), the main source of energy in cells, must be bound to a magnesium ion in order to be biologically active. What is called ATP is often actually Mg-ATP. <ref>"Magnesium" Centre for Cancer Education, University of Newcastle upon Tyne. http://cancerweb.ncl.ac.uk/cgi-bin/omd?magnesium</ref> === Nucleic acids=== [[Nucleic acid]]s have an important range of interactions with Mg<sup>2+</sup>. The binding of Mg<sup>2+</sup> to [[DNA]] and [[RNA]] stabilises structure; this can be observed in the increased melting temperature (''T''<sub>m</sub>) of double-stranded DNA in the presence of Mg<sup>2+</sup>.<ref name="Cowan 1995"/> Additionally, [[ribosome]]s contain large amounts of Mg<sup>2+</sup> and the stabilisation provided is essential to the complexation of this ribo-protein.<ref name="Sperazza 1983">{{cite journal| last=Sperazza| first= J.M.| coauthors= Spremulli, L.L. | year=1983| title= Quantitation of cation binding to wheat grem ribosomes: influences on subunit association equlibria and ribosome activity| journal= Nucleic Acids Research| volume= 11| pages= 2665–2679| doi=10.1093/nar/11.9.2665| pmid=6856472}}</ref> A large number of enzymes involved in the biochemistry of nucleic acids bind Mg<sup>2+</sup> for activity, using the ion for both activation and catalysis. Finally, the autocatalysis of many [[ribozymes]] (enzymes containing only RNA) is Mg<sup>2+</sup> dependent (e.g. the yeast mitochondrial group II self splicing introns<ref name="Smith 1995">{{cite journal| last=Smith| first= R.L.| coauthors= Thompson, L.J., and Maguire, M.E. | year=1995| title= Cloning and characterization of MgtE, a putative new class of Mg<sup>2+</sup> transporter from Bacillus firmus OF4| journal= Journal of Bacteriology| volume= 177| pages= 1233–1238}}</ref>). Magnesium ions can be critical in maintaining the positional integrity of closely clustered phosphate groups. These clusters appear in numerous and distinct parts of the [[cell nucleus]] and [[cytoplasm]]. For instance hexahydrated Mg<sup>2+</sup> ions bind in the deep [[DNA|major groove]] and at the outer mouth of A-form nucleic acid [[duplex]]es<ref name=ref1>[http://nar.oxfordjournals.org/cgi/content/abstract/28/8/1760 Hexahydrated magnesium ions bind in the deep major groove and at the outer mouth of A-form nucleic acid duplexes - Robinson et al. 28 (8): 1760 - Nucleic Acids Research<!-- Bot generated title -->]</ref>. ===Cell membranes and walls=== Biological [[cell membrane]]s and [[cell wall]]s are polyanionic surfaces. This has important implications for the transport of ions, particularly because it has been shown that different membranes preferentially bind different ions.<ref name="Cowan 1995"/> Both Mg<sup>2+</sup> and Ca<sup>2+</sup> regularly stabilise membranes by the cross-linking of carboxylated and phosphorylated head groups of lipids. However, the envelope membrane of ''[[E. coli]]'' has also been shown to bind Na<sup>+</sup>, K<sup>+</sup>, Mn<sup>2+</sup> and Fe<sup>3+</sup>. The transport of ions is dependent on both the concentration gradient of the ion and the electric potential (ΔΨ) across the membrane, which will be affected by the charge on the membrane surface. For example, the specific binding of Mg<sup>2+</sup> to the [[chloroplast]] envelope has been implicated in a loss of photosynthetic efficiency by the blockage of K<sup>+</sup> uptake and the subsequent acidification of the chloroplast stroma.<ref name="Berkowitz 1993"/> ===Proteins=== The Mg<sup>2+</sup> ion tends to bind only weakly to [[protein]]s ([[Acid dissociation constant|''K''<sub>a</sub>]] ≤ 10<sup>5</sup><ref name="Cowan 1995"/>) and this can be exploited by the cell to switch [[enzymatic]] activity on and off by changes in the local concentration of Mg<sup>2+</sup>. Although the concentration of free cytoplasmic Mg<sup>2+</sup> is on the order of 1 mmol/L, the total Mg<sup>2+</sup> content of animal cells is 30 mmol/L<ref name="Ebel 1980">{{cite journal| last=Ebel| first= H.| coauthors= Gunther, T. | year= 1980| title= Magnesium metabolism: a review| journal= Journal of Clinical Chemistry and Clinical Biochemistry| volume= 18| pages= 257–270}}</ref> and in plants the content of leaf endodermal cells has been measured at values as high as 100 mmol/L (Stelzer ''et al.'', 1990), much of which is buffered in storage compartments. The cytoplasmic concentration of free Mg<sup>2+</sup> is buffered by binding to chelators (e.g. ATP), but also more importantly by storage of Mg<sup>2+</sup> in intracellular compartments. The transport of Mg<sup>2+</sup> between intracellular compartments may be a major part of regulating enzyme activity. The interaction of Mg<sup>2+</sup> with proteins must also be considered for the transport of the ion across biological membranes. ===Manganese=== In biological systems, only [[manganese]] (Mn<sup>2+</sup>) is readily capable of replacing Mg<sup>2+</sup>, and only in a limited set of circumstances. Mn<sup>2+</sup> is very similar to Mg<sup>2+</sup> in terms of its chemical properties, including inner and outer shell complexation. Mn<sup>2+</sup> effectively binds ATP and allows hydrolysis of the energy molecule by most ATPases. Mn<sup>2+</sup> can also replace Mg<sup>2+</sup> as the activating ion for a number of Mg<sup>2+</sup>-dependent enzymes, although some enzyme activity is usually lost.<ref name="Cowan 1995"/> Sometimes such enzyme metal preferences vary among closely related species: for example is that the [[reverse transcriptase]] enzyme of [[lentivirus]]es like [[HIV]], [[SIV]] and [[FIV]] is typically dependent on Mg<sup>2+</sup>, whereas the analogous enzyme for other [[retrovirus]]es prefers Mn<sup>2+</sup>. === Importance in drug binding === An article<ref name=ref2>2. [http://www.nature.com/nature/journal/v413/n6858/abs/413814a0.html]</ref> investigating the structural basis of interactions between clinically reelevant antibiotics and the 50S ribosome appeared in Nature in October 2001. High resolution x-ray crystallography established that these antibiotics only associate with the 23S rRNA of a ribosomal subunit, and no interactions are formed with a subunit's protein portion. The article stresses that the results show "the importance of putative Mg<sup>2+</sup> ions for the binding of some drugs". ==Measuring magnesium in biological samples== ===By radioactive isotopes=== The use of radioactive tracer elements in ion uptake assays allows the calculation of km, Ki and Vmax and determines the initial change in the ion content of the cells. <sup>28</sup>Mg decays by the emission of a high energy beta or gamma particle, which can be measured using a scintillation counter. However, the radioactive half-life of <sup>28</sup>Mg, the most stable of the radioactive magnesium isotopes, is only 21 hours. This severely restricts the experiments involving the nuclide. Additionally, since 1990 no facility has routinely produced <sup>28</sup>Mg and the price per mCi is now predicted to be approximately US$30,000.<ref name="Maguire 2002">{{cite journal| last=Maguire| first= M.E.| coauthors= Cowan, J.A. | year=2002| title= Magnesium chemistry and biochemistry| journal=BioMetals| volume= 15| pages= 203–210| doi=10.1023/A:1016058229972}}</ref> The chemical nature of Mg<sup>2+</sup> is such that it is closely approximated by few other cations.<ref name="Tevelev 1995">{{cite book| last=Tevelev| first= A.| coauthors= Cowan, J.A. | year=1995| title= Metal substitution as a probe of the biological chemistry of magnesium ion| work=The Biological Chemistry of Magnesium| editor=J.A. Cowan | location=New York| publisher=VCH}}</ref> However, Co<sup>2+</sup>, Mn<sup>2+</sup> and Ni<sup>2+</sup> have been used successfully to mimic the properties of Mg<sup>2+</sup> in some enzyme reactions, and radioactive forms of these elements have been employed successfully in cation transport studies. The difficulty of using metal ion replacement in the study of enzyme function is that the relationship between the enzyme activities with the replacement ion compared to the original is very difficult to ascertain.<ref name="Tevelev 1995"/> ===By fluorescent indicators=== A number of chelators of divalent cations have different fluorescence spectra in the bound and unbound states.<ref name="Drakenberg 1995">{{cite book| last=Drakenberg| first= T. | year= 1995| title= Physical methods for studying the biological chemistry of magnesium| work= The Biological Chenistry of Magnesium| editor=J.A. Cowan| location=New York| publisher=VCH}}</ref> Chelators for Ca<sup>2+</sup> are well established, have high affinity for the cation, and low interference from other ions. Mg<sup>2+</sup> chelators lag behind and the major fluorescence dye for Mg<sup>2+</sup> (mag-fura 2<ref name="Raju 1989">{{cite journal| last=Raju| first= B.| coauthors= Murphy, E., Levy, L.A., Hall, R.D., and London, R.E. | year=1989| title= A fluorescent indicator for measuring cytosolic free magnesium| journal= Am J Physiol Cell Physiol| volume= 256| pages= C540–548}}</ref>) actually has a higher affinity for Ca<sup>2+</sup>.<ref name="Grubbs 2002">{{cite journal| last=Grubbs| first= R.D. | year= 2002| title= Intracellular magnesium and magnesium buffering| journal=BioMetals| volume= 15| pages= 251–259| doi=10.1023/A:1016026831789}}</ref> This limits the application of this dye to cell types where the resting level of Ca<sup>2+</sup> is < 1 μM and does not vary with the experimental conditions under which Mg<sup>2+</sup> is to be measured. Recently, Otten ''et al.'' (2001) have described work into a new class of compounds that may prove more useful, having significantly better binding affinities for Mg<sup>2+</sup>.<ref name="Otten 2001">{{cite journal| last=Otten| first= P.A.| coauthors= London, R.E., and Levy, L.A. | year=2001| title= 4-Oxo-4H-quinolizine-3-carboxylic acids as Mg<sup>2+</sup> selective, fluorescent indicators| journal= Bioconjugate Chemistry| volume= 12| pages= 203–212| doi=10.1021/bc000087d}}</ref> The use of the fluorescent dyes is limited to measuring the free Mg<sup>2+</sup>. If the ion concentration is buffered by the cell by chelation or removal to subcellular compartments, the measured rate of uptake will only give minimum values of km and Vmax. ===By electrophysiology=== First, ion-specific microelectrodes can be used to measure the internal free ion concentration of cells and organelles. The major advantages are that readings can be made from cells over relatively long periods of time, and that unlike dyes very little extra ion buffering capacity is added to the cells.<ref name="Gunzel 2002">{{cite journal| last=Gunzel| first= D.| coauthors= Schlue, W.-R. | year= 2002| title= Determination of [Mg<sup>2+</sup>]i - an update on the use of Mg<sup>2+</sup>-selective electrodes| journal=BioMetals| volume= 15| pages= 237–249| doi=10.1023/A:1016074714951}}</ref> Second, the technique of two-electrode voltage-clamp allows the direct measurement of the ion flux across the membrane of a cell.<ref name="Hille 1992 ch2">{{cite book| last=Hille| first= B. | year=1992| title= Ionic channels of excitable membranes| location=Sunderland| publisher= Sinauer Associates Inc.| chapter=2}}</ref> The membrane is held at an electric potential and the responding current is measured. All ions passing across the membrane contribute to the measured current. Third, the technique of patch-clamp which uses isolated sections of natural or artificial membrane in much the same manner as voltage-clamp but without the secondary effects of a cellular system. Under ideal conditions the conductance of individual channels can be quantified. This methodology gives the most direct measurement of the action of ion channels.<ref name="Hille 1992 ch2"/> ===By absorption spectrography=== Flame atomic absorption spectroscopy (AAS) determines the total magnesium content of a biological sample.<ref name="Drakenberg 1995"/> This method is destructive; biological samples must be broken down in concentrated acids to avoid clogging the fine nebulising apparatus. Beyond this the only limitation is that samples need to be in a volume of approximately 2 mL and at a concentration range of 0.1 – 0.4 µmol/L for optimum accuracy. As this technique cannot distinguish between Mg<sup>2+</sup> already present in the cell and that taken up during the experiment only content not uptake can be quantified. Inductively coupled plasma (ICP) using either the mass spectrometry (MS) or atomic emission spectroscopy (AES) modifications also allows the determination of the total ion content of biological samples.<ref name="Dean 1997">See Chapters 5 and 6 in {{cite book| last=Dean| first= J.R. | year= 1997| title= Atomic Absorption and Plasma Spectroscopy| location=Chichester| publisher= John Wiley & Sons}} for descriptions of the methodology as applied to analytical chemistry.</ref> These techniques are more sensitive than flame AAS and are capable of measuring the quantities of multiple ions simultaneously. However, they are also significantly more expensive. ==Magnesium transport== {{main|Magnesium transport}} The chemical and biochemical properties of Mg<sup>2+</sup> present the cellular system with a significant challenge when transporting the ion across biological membranes. The dogma of ion transport states that the transporter recognises the ion then progressively removes the water of hydration, removing most or all of the water at a selective pore before releasing the ion on the far side of the membrane.<ref name="Hille 1992 ch11">Hille, 1992. Chapter 11</ref> Due to the properties of Mg<sup>2+</sup>, large volume change from hydrated to bare ion, high energy of hydration and very low rate of ligand exchange in the inner [[coordination sphere]], these steps are probably more difficult than for most other ions. To date, only the ZntA protein of Paramecium has been shown to be a Mg<sup>2+</sup> channel.<ref name="Haynes 2002">{{cite journal| last=Haynes| first= W.J.| coauthors= Kung, C., Saimi, Y., and Preston, R.R. | year=2002| title= An exchanger-like protein underlies the large Mg<sup>2+</sup> current in Paramecium| journal= PNAS| volume= 99| pages= 15717–15722| doi=10.1073/pnas.242603999| pmid=12422021}}</ref> The mechanisms of Mg<sup>2+</sup> transport by the remaining proteins are beginning to be uncovered with the first three dimensional structure of a Mg<sup>2+</sup> transport complex being solved in 2004<ref name="Warren 2004">{{cite journal| last=Warren| first= M.A. | coauthors=Kucharski, L.M., Veenstra, A., Shi, L., Grulich, P.F., and Maguire, M.E.|year=2004| title= The CorA Mg<sup>2+</sup> transporter is a homotetramer| journal=Journal of Bacteriology | volume=186| pages=4605–4612| doi=10.1128/JB.186.14.4605-4612.2004| pmid=15231793}}</ref>. The hydration shell of the Mg<sup>2+</sup> ion has a very tightly bound inner shell of six water molecules and a relatively tightly bound second shell containing 12 – 14 water molecules (Markham ''et al.'', 2002). Thus recognition of the Mg<sup>2+</sup> ion probably requires some mechanism to interact initially with the hydration shell of Mg<sup>2+</sup>, followed by a direct recognition/binding of the ion to the protein.<ref name="Maguire 2002"/> Due to the strength of the inner sphere complexation between Mg<sup>2+</sup> and any ligand, multiple simultaneous interactions with the transport protein at this level might significantly retard the ion in the transport pore. Hence, it is possible that much of the hydration water is retained during transport, allowing the weaker (but still specific) outer sphere coordination. In spite of the mechanistic difficulty, Mg<sup>2+</sup> must be transported across membranes, and a large number of Mg<sup>2+</sup> fluxes across membranes from a variety of systems have been described.<ref name="Gardner 2003">{{cite journal| last=Gardner| first= R.C. | year= 2003| title= Genes for magnesium transport| journal= Current Opinion in Plant Biology| volume= 6| pages= 263–267| doi=10.1016/S1369-5266(03)00032-3}}</ref> However, only a small selection of Mg<sup>2+</sup> transporters have been characterised at the molecular level. === Ligand ion channel blockade === [[Magnesium]] [[ion]]s (Mg<sup>2+</sup>) in [[cellular biology]] are usually in almost all senses opposite to [[calcium in biology|Ca<sup>2+</sup>]] ions, because they are [[Bivalent (chemistry)|bivalent]] too, but have greater electronegativity and thus hold on to water molecules stronger, preventing passage through the channel (even though magnesium is smaller). Thus Mg<sup>2+</sup> ions block Ca<sup>2+</sup> channels ([[NMDA channel]]s) for example, etc. ==Plant physiology of magnesium== The previous sections have dealt in detail with the chemical and biochemical aspects of Mg<sup>2+</sup> and its transport across cellular membranes. This section will apply this knowledge to aspects of whole plant physiology, in an attempt to show how these processes interact with the larger and more complex environment of the multicellular organism. ===Nutritional requirements and interactions=== Mg<sup>2+</sup> is essential for plant growth and is present in higher plants in amounts on the order of 80 μmol g<sup>-1</sup> dry weight.<ref name="Marschner 1995"/> The amounts of Mg<sup>2+</sup> vary in different parts of the plant and are dependent upon nutritional status. In times of plenty, excess Mg<sup>2+</sup> may be stored in vascular cells (Stelzer ''et al.'', 1990;<ref name="Shaul 1999"/> and in times of starvation Mg<sup>2+</sup> is redistributed, in many plants, from older to newer leaves.<ref name="Marschner 1995"/><ref name="Laing 2000">{{cite journal| last=Laing| first= W.| coauthors= Greer, D., Sun, O., Beets, P., Lowe, A., and Payn, T. | year=2000| title= Physiological impacts of Mg deficiency in Pinus radiata: growth and photosynthesis| journal= New Phytol| volume= 146| pages= 47–57| doi=10.1046/j.1469-8137.2000.00616.x}}</ref> Mg<sup>2+</sup> is taken up into plants via the roots. Interactions with other cations in the [[Rhizosphere (ecology)|rhizosphere]] can have a significant effect on the uptake of the ion.(Kurvits and Kirkby, 1980;<ref name="Heenan 1981">{{cite journal| last=Heenan| first= D.P.| coauthors= Campbell, L.C. | year=1981| title= Influence of potassium and manganese on growth and uptake of magnesium by soybeans (Glycine max (L.) Merr. cv Bragg| journal=Plant Soil| volume= 61| pages= 447–456| doi=10.1007/BF02182025}}</ref> The structure of root cell walls is highly permeable to water and ions, and hence ion uptake into root cells, can occur anywhere from the root hairs to cells located almost in the centre of the root (limited only by the [[Casparian strip]]). Plant cell walls and membranes carry a great number of negative charges and the interactions of cations with these charges is key to the uptake of cations by root cells allowing a local concentrating effect.<ref name="Hope 1952">{{cite journal| last=Hope| first= A.B.| coauthors= Stevens, P.G. | year=1952| title= Electrical potential differences in bean roots on their relation to salt uptake| journal= Australian Journal of Scientific Research, Series B| volume= 5| pages= 335–343}}</ref> Mg<sup>2+</sup> binds relatively weakly to these charges, and can be displaced by other cations, impeding uptake and causing deficiency in the plant. Within individual plant cells the Mg<sup>2+</sup> requirements are largely the same as for all cellular life; Mg<sup>2+</sup> is used to stabilise membranes, is vital to the utilisation of ATP, is extensively involved in the nucleic acid biochemistry, and is a cofactor for many enzymes (including the ribosome). Also, Mg<sup>2+</sup> is the coordinating ion in the chlorophyll molecule. It is the intracellular compartmentalisation of Mg<sup>2+</sup> in plant cells that leads to additional complexity. Four compartments within the plant cell have reported interactions with Mg<sup>2+</sup>. Initially Mg<sup>2+</sup> will enter the cell into the cytoplasm (by an as yet unidentified system), but free Mg<sup>2+</sup> concentrations in this compartment are tightly regulated at relatively low levels (≈2 mmol/L) and so any excess Mg<sup>2+</sup> is either quickly exported or stored in the second intracellular compartment, the vacuole.<ref>Section 8.5.2 in Marschner, 1995</ref> The requirement for Mg<sup>2+</sup> in mitochondria has been demonstrated in yeast<ref name="Bui 1999">{{cite journal| last=Bui| first= D.M.| coauthors= Gregan, J., Jarosch, E., Ragnini, A., and Schweyen, R.J. | year=1999| title= The bacterial magnesium transporter CorA can functionally substitute for its putative homologue Mrs2p in the yeast inner mitochondrial membrane| journal= Journal of Biological Chemistry| volume= 274| pages= 20438–20443| doi=10.1074/jbc.274.29.20438| pmid=10400670}}</ref> and it seems highly likely that the same will apply in plants. The chloroplasts also require significant amounts of internal Mg<sup>2+</sup>, and low concentrations of cytoplasmic Mg<sup>2+</sup>.<ref name="Demmig 1979">{{cite journal| last=Demmig| first= B.| coauthors= Gimmler, H. | year= 1979| title= Effect of divalent cations on cation fluxes across the chloroplast envelope and on photosynthesis of intact chloroplasts| journal=Zeitschrift fur Naturforschung| volume= 24C| pages= 233–241}}</ref><ref name="Huber 1980">{{cite journal| last=Huber| first= S.C.| coauthors= Maury, W.J. | year=1980| title= Effects of magnesium on intact chloroplasts| journal= Plant Physiology| volume= 65| pages= 350–354}}</ref> In addition, it seems likely that the other subcellular organelles (e.g. Golgi, endoplasmic reticulum, etc) also require Mg<sup>2+</sup>. ===Distributing magnesium ions within the plant=== Once in the cytoplasmic space of root cells Mg<sup>2+</sup>, along with the other cations, is probably transported radially into the stele and the vascular tissue.<ref>Section 2.7 in Marschner, 1995</ref> From the cells surrounding the xylem the ions are released or pumped into the xylem and carried up through the plant. In the case of Mg<sup>2+</sup>, which is highly mobile in both the xylem and phloem,<ref>Section 3.3 in Marschner, 1995</ref> the ions will be transported to the top of the plant and back down again in a continuous cycle of replenishment. Hence, uptake and release from vascular cells is probably a key part of whole plant Mg<sup>2+</sup> homeostasis. Figure 1 shows how few processes have been connected to their molecular mechanisms (only vacuolar uptake has been associated with a transport protein, AtMHX). The diagram shows a schematic of a plant and the putative processes of Mg<sup>2+</sup> transport at the root and leaf where Mg<sup>2+</sup> is loaded and unloaded from the vascular tissues.<ref name="Marschner 1995"/> Mg<sup>2+</sup> is taken up into the root cell wall space (1) and interacts with the negative charges associated with the cell walls and membranes. Mg<sup>2+</sup> may be taken up into cells immediately (symplastic pathway) or may travel as far as the Casparian band (4) before being absorbed into cells (apoplastic pathway; 2). The concentration of Mg<sup>2+</sup> in the root cells is probably buffered by storage in root cell vacuoles (3). Note that cells in the root tip do not contain vacuoles. Once in the root cell cytoplasm Mg<sup>2+</sup> travels towards the centre of the root by [[plasmodesmata]], where it is loaded into the xylem (5) for transport to the upper parts of the plant. When the Mg<sup>2+</sup> reaches the leaves it is unloaded from the xylem into cells (6) and again is buffered in vacuoles (7). Whether cycling of Mg<sup>2+</sup> into the phloem occurs via general cells in the leaf (8) or directly from xylem to phloem via [[transfer cells]] (9) is unknown. Mg<sup>2+</sup> may return to the roots in the phloem sap. [[Image:whole plant mg transport.png|frame|center|Figure 1: Magnesium in the whole plant]] When a Mg<sup>2+</sup> ion has been absorbed by a cell requiring it for metabolic processes, it is generally assumed that the ion stays in that cell for as long as the cell is active.<ref name="Marschner 1995"/> In vascular cells this is not always the case; in times of plenty Mg<sup>2+</sup> is stored in the vacuole, takes no part in the day-to-day metabolic processes of the cell (Stelzer ''et al.'', 1990) , and is released at need. But for most cells it is death by senescence or injury that releases Mg<sup>2+</sup> and many of the other ionic constituents, recycling them into healthy parts of the plant. Additionally, when Mg<sup>2+</sup> in the environment is limiting some species are able to mobilise Mg<sup>2+</sup> from older tissues.<ref name="Laing 2000"/> These processes involve the release of Mg<sup>2+</sup> from its bound and stored states and its transport back into the vascular tissue, where it can be distributed to the rest of the plant. In times of growth and development Mg<sup>2+</sup> is also remobilised within the plant as source and sink relationships change.<ref name="Marschner 1995"/> The homeostasis of Mg<sup>2+</sup> within single plant cells is maintained by processes occurring at the plasma membrane and at the vacuole membrane (see Figure 2). The major driving force for the translocation of ions in plant cells is ΔpH.<ref>Section 2.4 in Marschner, 1995</ref> H<sup>+</sup>-ATPases pump H<sup>+</sup> ions against their concentration gradient to maintain the pH differential that can be used for the transport of other ions and molecules. H<sup>+</sup> ions are pumped out of the cytoplasm into the extracellular space or into the vacuole. The entry of Mg<sup>2+</sup> into cells may occur through one of two pathways, via channels using the ΔΨ (negative inside) across this membrane or by symport with H<sup>+</sup> ions. To transport the Mg<sup>2+</sup> ion into the vacuole requires a Mg<sup>2+</sup>/H<sup>+</sup> antiport transporter (such as AtMHX). It is interesting to note that the H<sup>+</sup>-ATPases are dependent on Mg<sup>2+</sup> (bound to ATP) for activity, so that Mg<sup>2+</sup> is required to maintain its own homeostasis. A schematic of a plant cell is shown including the four major compartments currently recognised as interacting with Mg<sup>2+</sup>. H<sup>+</sup>-ATPases maintain a constant ΔpH across the plasma membrane and the vacuole membrane. Mg<sup>2+</sup> is transported into the vacuole using the energy of ΔpH (in ''A. thaliana'' by AtMHX). Transport of Mg<sup>2+</sup> into cells may use either the negative ΔΨ or the ΔpH. The transport of Mg<sup>2+</sup> into mitochondria probably uses ΔΨ as in the mitochondria of yeast, and it is likely that chloroplasts take Mg<sup>2+</sup> by a similar system. The mechanism and the molecular basis for the release of Mg<sup>2+</sup> from vacuoles and from the cell is not known. Likewise the light-regulated Mg<sup>2+</sup> concentration changes in chloroplasts are not fully understood, but do require the transport of H<sup>+</sup> ions across the thylakoid membrane. [[Image:magnesium in plant cell.png|frame|center|Figure 2: Magnesium in the plant cell]] ===Magnesium, chloroplasts and photosynthesis=== Mg<sup>2+</sup> is the coordinating metal ion in the chlorophyll molecule, and in plants where the ion is in high supply about 6% of the total Mg<sup>2+</sup> is bound to chlorophyll.<ref name="Marschner 1995"/><ref name="Scott 1990a">{{cite journal| last=Scott| first= B.J.| coauthors= Robson, A.D. | year=1990| title= Distribution of magnesium in subterranean clover (''Trifolium subterranean'' L.) in relation to supply| journal= Australian Journal of Agricultural Research| volume= 41| pages= 499–510| doi=10.1071/AR9900499}}</ref><ref name="Scott 1990b">{{cite journal| last=Scott| first= B.J.| coauthors= Robson, A.D. | year=1990b| title= Changes in the content and form of magnesium in the first trifoliate leaf of subterranean clover under altered or constant root supply| journal= Australian Journal of Agricultural Research| volume= 41| pages= 511–519| doi=10.1071/AR9900511}}</ref> Thylakoid stacking is stabilised by Mg<sup>2+</sup> and is important for the efficiency of photosynthesis, allowing phase transitions to occur.<ref name="Fork 1986">{{cite journal| last=Fork| first= D.C. | year= 1986| title= The control by state transitions of the distribution of excitation energy in photosynthesis| journal= Annual Review of Plant Physiology and Plant Molecular Biology| volume= 37| pages= 335–361| doi=10.1146/annurev.arplant.37.1.335}}</ref> Mg<sup>2+</sup> is probably taken up into chloroplasts to the greatest extent during the light induced development from proplastid to chloroplast or etioplast to chloroplast. At these times the synthesis of chlorophyll and the biogenesis of the thylakoid membrane stacks absolutely require the divalent cation.<ref name="Gregory 1989">{{cite book| last=Gregory| first= R.P.F. | year= 1989| title= Structure and function of the photosynthesising cell| work= Biochemistry of Photosnythesis| location=New York| publisher= John Wiley and Sons}}</ref><ref name="Lu 1995">{{cite journal| last=Lu| first= Y.-K.| coauthors= Chen, Y.-R., Yang, C.-M., and Ifuku, K. | year=1995| title= Influence of Fe- and Mg-deficiency on the thylakoid membranes of a chlorophyll-deficient ch5 mutant of Arabidopsis thaliana| journal= Botanical Bulletin of Academia Sinica| volume= 36}}</ref> Whether Mg<sup>2+</sup> is able to move into and out of chloroplasts after this initial developmental phase has been the subject of several conflicting reports. Deshaies ''et al.'' (1984) found that Mg<sup>2+</sup> did move in and out of isolated chloroplasts from young pea plants,<ref name="Deshaies 1984">{{cite journal| last=Deshaies| first= R.J.| coauthors= Fish, L.E., and Jagendorf, A.T. | year= 1984| title= Permeability of chloroplast envelopes to Mg<sup>2+</sup>| journal= Plant Physiology| volume= 74| pages=956–961}}</ref> but Gupta and Berkowitz (1989) were unable to reproduce the result using older spinach chloroplasts.<ref name="Gupta 1989">{{cite journal| last=Gupta| first= A.S.| coauthors= Berkowitz, G.A. | year=1989| title= Development and use of chlorotetracycline fluorescence as a measurement assay of chloroplast envelope-bound Mg<sup>2+</sup>| journal= Plant Physiology| volume= 89| pages= 753–761}}</ref> Deshaies ''et al.'' had stated in their paper that older pea chloroplasts showed less significant changes in Mg<sup>2+</sup> content than those used to form their conclusions. Perhaps the relative proportion of immature chloroplasts present in the preparations might explain these observations. The metabolic state of the chloroplast changes considerably between night and day. During the day the chloroplast is actively harvesting the energy of light and converting it into chemical energy. The activation of the metabolic pathways involved comes from the changes in the chemical nature of the stroma on the addition of light. H<sup>+</sup> is pumped out of the stroma (into both the cytoplasm and the lumen) leading to an alkaline pH.<ref name="Heldt 1973">{{cite journal| last=Heldt| first= H.W.| coauthors= Werdan, K., Milovancev, M., and Geller, G. | year=1973| title= Alkalization of the chloroplast stroma caused by light-dependent proton flux into the thylakoid space| journal= Biochimica et Biophysica Acta| volume= 314| pages= 224–241| doi=10.1016/0005-2728(73)90137-0}}</ref><ref name="Hind 1974">{{cite journal| last=Hind| first= G.| coauthors= Nakatani, H.Y., and Izawa, S. | year=1974| title= Light-dependent redistribution of ions in suspensions of chloroplast thylakoid membranes| journal= Proceedings of the National Academy of Sciences of the United States of America| volume= 71| pages= 1484–1488| doi=10.1073/pnas.71.4.1484| pmid=4524652}}</ref> Mg<sup>2+</sup> (along with K<sup>+</sup>) is released from the lumen into the stroma, in an electroneutralisation process to balance the flow of H<sup>+</sup>.<ref name="Bulychev 1976">{{cite journal| last=Bulychev| first= A.A.| coauthors= Vredenberg, W.J. | year=1976| title= Effect of ionophores A-23187 and nigericin on the light induced redistribution of magnesium potassium and hydrogen ions across the thylakoid membrane| journal= Biochimica et Biophysica Acta| volume= 449| pages= 48–58| doi=10.1016/0005-2728(76)90006-2}}</ref><ref name="Krause 1977">{{cite journal| last=Krause| first= G.H. | year=1977| title= Light-induced movement of magnesium ions in intact chloroplasts. Spectroscopic determination with Eriochrome Blue SE| journal= Biochimica et Biophysica Acta| volume= 460| pages= 500–510| doi=10.1016/0005-2728(77)90088-3}}</ref><ref name="Portis 1981">{{cite journal| last=Portis| first= A.R. | year=1981| title= Evidence of a low stromal Mg<sup>2+</sup> concentration in intact chloroplasts in the dark| journal= Plant Physiology| volume= 67| pages= 985–989}}</ref><ref name="Ishijima 2003">{{cite journal| last=Ishijima| first= S.| coauthors= Uchibori, A., Takagi, H., Maki, R., and Ohnishi, M. | year=2003| title= Light-induced increase in free Mg<sup>2+</sup> concentration in spinach chloroplasts: Measurement of free Mg<sup>2+</sup> by using a fluorescent probe and intensity of stromal alkalinization| journal= Archives of Biochemistry and Biophysics| volume= 412| pages= 126–132| doi=10.1016/S0003-9861(03)00038-9}}</ref> Finally, thiol groups on enzymes are reduced by a change in the redox state of the stroma.<ref name="Sharkey 1998">{{cite journal| last=Sharkey| first= T.D. | year=1998| title= Photosynthetic carbon reduction| work= Photosynthesis: A Comprehensive Treatise| editor= A. Raghavendra| location=Cambridge| publisher=Cambridge University Press| pages=111–122}}</ref> Examples of enzymes activated in response to these changes are fructose 1,6-bisphosphatase, sedoheptulose bisphosphatase and ribulose-1,5-bisphosphate carboxylase.<ref name="Black 1995b"/><ref name="Marschner 1995"/><ref name="Sharkey 1998"/> During the dark period, if these enzymes were active a wasteful cycling of products and substrates would occur. Two major classes of the enzymes that interact with Mg<sup>2+</sup> in the stroma during the light phase can be identified.<ref name="Black 1995b"/> Firstly, enzymes in the glycolytic pathway most often interact with two atoms of Mg<sup>2+</sup>. The first atom is as an allosteric modulator of the enzymes’ activity, while the second forms part of the active site and is directly involved in the catalytic reaction. The second class of enzymes include those where the Mg<sup>2+</sup> is complexed to nucleotide di- and tri-phosphates (ADP and ATP) and the chemical change involves phosphoryl transfer. Mg<sup>2+</sup> may also serve in a structural maintenance role in these enzymes (e.g. enolase). ===Magnesium stress=== Plant stress responses can be observed in plants that are under or over supplied with Mg<sup>2+</sup>. The first observable signs of Mg<sup>2+</sup> stress in plants for both starvation and toxicity is a depression of the rate of photosynthesis, presumably because of the strong relationships between Mg<sup>2+</sup> and chloroplasts/chlorophyll. In pine trees, even before the visible appearance of yellowing and necrotic spots, the photosynthetic efficiency of the needles drops markedly.<ref name="Laing 2000"/> In Mg<sup>2+</sup> deficiency, reported secondary effects include carbohydrate immobility, loss of RNA transcription and loss of protein synthesis.<ref>Section 8.5.6 of Marschner, 1995</ref> However, due to the mobility of Mg<sup>2+</sup> within the plant, the deficiency phenotype may be present only in the older parts of the plant. For example, in Pinus radiata starved of Mg<sup>2+</sup> one of the earliest identifying signs is the chlorosis in the needles on the lower branches of the tree. This is because Mg<sup>2+</sup> has been recovered from these tissues and moved to growing (green) needles higher in the tree.<ref name="Laing 2000"/> A Mg<sup>2+</sup> deficit can be caused by the lack of the ion in the media (soil), but more commonly comes from inhibition of its uptake.<ref name="Marschner 1995"/> Mg<sup>2+</sup> binds quite weakly to the negatively charged groups in the root cell walls, so that excesses of other cations such as K<sup>+</sup>, NH<sup>4+</sup>, Ca<sup>2+</sup> and Mn<sup>2+</sup> can all impede uptake.(Kurvits and Kirkby, 1980;<ref name="Heenan 1981"/> In acid soils Al<sup>3+</sup> is a particularly strong inhibitor of Mg<sup>2+</sup> uptake.<ref name="Rengel 1989">{{cite journal| last=Rengel| first= Z.| coauthors= Robinson, D.L. | year=1989| title= Competitive Al3+ inhibition of net Mg<sup>2+</sup> uptake by intact Lolium multiflorum roots. I. Kinetics| journal= Plant Physiology| volume= 91| pages= 1407–1413}}</ref><ref name="Marschner 1991">{{cite book| last=Marschner| first= H. | year=1991| title= Root-induced changes in the avaibility of micronutrients in the rhizosphere| work= Plant Roots: The Hidden Half| editor=Y. Waisel, A. Eshel, and U. Kafikfai| location=New York| publisher=Marcel Dekker}}</ref> The inhibition by Al<sup>3+</sup> and Mn<sup>2+</sup> is more severe than can be explained by simple displacement, hence it is possible that these ions bind to the Mg<sup>2+</sup> uptake system directly.<ref name="Marschner 1995"/> In bacteria and yeast, such binding by Mn<sup>2+</sup> has already been observed. Stress responses in the plant develop as cellular processes halt due to a lack of Mg<sup>2+</sup> (e.g. maintenance of ΔpH across the plasma and vacuole membranes). Interestingly, in Mg<sup>2+</sup>-starved plants under low light conditions the percentage of Mg<sup>2+</sup> bound to chlorophyll has been recorded at 50%.<ref name="Dorenstouter 1985">{{cite journal| last=Dorenstouter| first= H.| coauthors= Pieters, G.A., and Findenegg, G.R. | year= 1985| title= Distribution of magnesium between chloroplhyll and other photosynthetic functions in magnesium deficient 'sun' and 'shade' leaves of poplar| journal= Journal of Plant Nutrition| volume= 8| pages= 1088–1101}}</ref> Presumably, this imbalance has detrimental effects on other cellular processes. Mg<sup>2+</sup> toxicity stress is more difficult to develop. When Mg<sup>2+</sup> is plentiful the plants generally take up the ion and store it (Stelzer ''et al.'', 1990). However, if this is followed by drought then ionic concentrations within the cell can increase dramatically. High cytoplasmic Mg<sup>2+</sup> concentrations block a K<sup>+</sup> channel in the inner envelope membrane of the chloroplast, in turn inhibiting the removal of H<sup>+</sup> ions from the chloroplast stroma. This leads to an acidification of the stroma that inactivates key enzymes in carbon fixation, which all leads to the production of oxygen free radicals in the chloroplast that then cause oxidative damage.<ref name="Wu 1991">{{cite journal| last=Wu| first= W.| coauthors= Peters, J., and Berkowitz, G.A. | year=1991| title= Surface charge-mediated effects of Mg<sup>2+</sup> on K<sup>+</sup> flux across the chloroplast envelope membrane are associated with the regulation of stromal pH and photosynthesis| journal= Plant Physiology| volume= 97| pages= 580–587}}</ref> == External links == *[http://www.ctds.info/5_13_magnesium.html Magnesium Deficiency] *[http://www.mgwater.com/index.shtml The Magnesium Website]- Includes full text papers and textbook chapters by leading magnesium authorities Mildred Seelig, Jean Durlach, Burton M. Altura and Bella T. Altura. Links to over 300 articles discussing magnesium and magnesium deficiency. *[http://www.iom.edu/Object.File/Master/7/294/0.pdf Dietary Reference Intake] * [http://autism.healingthresholds.com/ Healing Thresholds] - description of research studies regarding supplementation with magnesium and other therapies for autism ==See also== *[[Ion channels]] ==References== References: * Findling, R.L., et al. 1997. "High-dose pyridoxine and magnesium administration in children with autistic disorder: an absence of salutary effects in a double-blind, placebo-controlled study." J Autism Dev Disord. 27(4):467-478. * Green, V.; Pituch, K.; Itchon, J.; Choi, A.; OReilly, M.; Sigafoo, J. 2006. "Internet Survey of Treatments Used by Parents of Children with Autism," Research in Developmental Disabilities. 27(1):70-84 * Lelord, G., et al. 1981. "Effects of pyridoxine and magnesium on autistic symptoms--initial observations." J Autism Dev Disord. 11(2):219-230. * Martineau, J., et al. 1985. "Vitamin B6, magnesium, and combined B6-Mg: therapeutic effects in childhood autism." Biol.Psychiatry 20(5):467-478. * Tolbert, L., et al. 1993. "Brief report: lack of response in an autistic population to a low dose clinical trial of pyridoxine plus magnesium." J Autism Dev Disord. 23(1):193-199. * Mousain-Bosc M. et al. 2006. "Improvement of neurobehavioral disorders in children supplemented with magnesium-vitamin B6. I. Attention deficit hyperactivity disorders." Magnes Res. 2006 Mar;19(1):46-52. * Mousain-Bosc M. et al. 2006. "Improvement of neurobehavioral disorders in children supplemented with magnesium-vitamin B6. II. Pervasive developmental disorder-autism." Magnes Res. 2006 Mar;19(1):53-62. {{reflist}} <!-- dead references *{{cite journal| last=Konrad| first= M.| coauthors= Schlingmann K.P. and Gudermann T. | year=2004) Insights into the molecular nature of magnesium homeostasis| journal= American Journal of Physiology: Renal physiology| volume=286| pages=F599–605| id= {{Entrez Pubmed|15001450}}| doi=10.1152/ajprenal.00312.2003| title=Insights into the molecular nature of magnesium homeostasis| pmid=15001450}} *{{cite journal| last=Kurvits| first= A.| coauthors=Kirkby, E.A. | year=1980| title= The uptake of nutrients by sunflower plants (Helianthus annuus) growing in a continuous flowing culture system, supplied with nitrate or ammonia as a nitrogen source| journal= Zeitschrift für Pflanzenernährung und Bodenkunde| volume= 143| pages= 140–149| doi=10.1002/jpln.19801430203}} *{{cite journal| last=Voets| first= T.| coauthors= Nilius B., Hoefs S., van der Kemp A.W., Droogmans G., Bindels R.J. and Hoenderop J.G. | year=2004) TRPM6 forms the Mg<sup>2+</sup> influx channel involved in intestinal and renal Mg<sup>2+</sup> absorption| journal= Journal of Biological Chemistry| volume= 279| pages= 19–25| id= {{Entrez Pubmed|14576148}}| doi=10.1074/jbc.M311201200| title=TRPM6 Forms the Mg2+ Influx Channel Involved in Intestinal and Renal Mg2+ Absorption| pmid=14576148}} --> </div> [[Category:Physiology]] [[Category:Plant physiology]] [[Category:Magnesium]] [[Category:Biology and pharmacology of chemical elements]] [[Category:Biological systems]]