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 chloroplasts in the Calvin cycle.
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. In yeast, mitochondrial magnesium deficiency is also leads to disease.
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++ ion in the chlorophyll molecule. The later effects of magnesium deficiency on plants are a significant reduction in growth and reproductive viability. Magnesium can also be toxic to plants, although this is typically seen only in drought conditions.
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. A number of genetically attributable hypomagnesemia disorders have also been identified in humans.
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).
The DRI upper tolerated limit for 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.) 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.
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.
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.
Green vegetables such as spinach provide magnesium because of the abundance of chlorophyll molecules which contain the ion. Nuts (especially cashews and almonds), seeds, and some whole grains 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 can also provide magnesium, but "soft" water does not contain the ion. Dietary surveys do not assess 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:
The U.S. RDA/RDV is 400 mg of magnesium.
In photosynthetic organisms Mg2+ 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.
The chemistry of the Mg2+ ion, as applied to enzymes, uses the full range of this ion’s unusual reaction chemistry to fulfill a range of functions. Mg2+ interacts with substrates, enzymes and occasionally both (Mg2+ may form part of the active site). Mg2+ 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 Mg2+ 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 Mg2+ is only rarely fully dehydrated during ligand binding, it may be a water molecule associated with the Mg2+ that is important rather than the ion itself. The Lewis acidity of Mg2+ (pKa 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.
Nucleic acids have an important range of interactions with Mg2+. The binding of Mg2+ to DNA and RNA stabilises structure; this can be observed in the increased melting temperature (Tm) of double-stranded DNA in the presence of Mg2+. Additionally, ribosomes contain large amounts of Mg2+ and the stabilisation provided is essential to the complexation of this ribo-protein. A large number of enzymes involved in the biochemistry of nucleic acids bind Mg2+ for activity, using the ion for both activation and catalysis. Finally, the autocatalysis of many ribozymes (enzymes containing only RNA) is Mg2+ dependent (e.g. the yeast mitochondrial group II self splicing introns).
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 Mg2+ ions bind in the deep major groove and at the outer mouth of A-form nucleic acid duplexes.
Biological cell membranes and cell walls 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. Both Mg2+ and Ca2+ 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+, K+, Mn2+ and Fe3+. 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 Mg2+ to the chloroplast envelope has been implicated in a loss of photosynthetic efficiency by the blockage of K+ uptake and the subsequent acidification of the chloroplast stroma.
The Mg2+ ion tends to bind only weakly to proteins (Ka ≤ 105) and this can be exploited by the cell to switch enzymatic activity on and off by changes in the local concentration of Mg2+. Although the concentration of free cytoplasmic Mg2+ is on the order of 1 mmol/L, the total Mg2+ content of animal cells is 30 mmol/L 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 Mg2+ is buffered by binding to chelators (e.g. ATP), but also more importantly by storage of Mg2+ in intracellular compartments. The transport of Mg2+ between intracellular compartments may be a major part of regulating enzyme activity. The interaction of Mg2+ with proteins must also be considered for the transport of the ion across biological membranes.
In biological systems, only manganese (Mn2+) is readily capable of replacing Mg2+, and only in a limited set of circumstances. Mn2+ is very similar to Mg2+ in terms of its chemical properties, including inner and outer shell complexation. Mn2+ effectively binds ATP and allows hydrolysis of the energy molecule by most ATPases. Mn2+ can also replace Mg2+ as the activating ion for a number of Mg2+-dependent enzymes, although some enzyme activity is usually lost. Sometimes such enzyme metal preferences vary among closely related species: for example is that the reverse transcriptase enzyme of lentiviruses like HIV, SIV and FIV is typically dependent on Mg2+, whereas the analogous enzyme for other retroviruses prefers Mn2+.
Second, the technique of two-electrode voltage-clamp allows the direct measurement of the ion flux across the membrane of a cell. 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.
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. 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.
The chemical and biochemical properties of Mg2+ 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. Due to the properties of Mg2+, 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 Mg2+ channel. The mechanisms of Mg2+ transport by the remaining proteins are beginning to be uncovered with the first three dimensional structure of a Mg2+ transport complex being solved in 2004.
The hydration shell of the Mg2+ 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 Mg2+ ion probably requires some mechanism to interact initially with the hydration shell of Mg2+, followed by a direct recognition/binding of the ion to the protein. Due to the strength of the inner sphere complexation between Mg2+ 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, Mg2+ must be transported across membranes, and a large number of Mg2+ fluxes across membranes from a variety of systems have been described. However, only a small selection of Mg2+ transporters have been characterised at the molecular level.
Mg2+ is taken up into plants via the roots. Interactions with other cations in the rhizosphere can have a significant effect on the uptake of the ion.(Kurvits and Kirkby, 1980; 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. Mg2+ 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 Mg2+ requirements are largely the same as for all cellular life; Mg2+ 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, Mg2+ is the coordinating ion in the chlorophyll molecule. It is the intracellular compartmentalisation of Mg2+ in plant cells that leads to additional complexity. Four compartments within the plant cell have reported interactions with Mg2+. Initially Mg2+ will enter the cell into the cytoplasm (by an as yet unidentified system), but free Mg2+ concentrations in this compartment are tightly regulated at relatively low levels (≈2 mmol/L) and so any excess Mg2+ is either quickly exported or stored in the second intracellular compartment, the vacuole. The requirement for Mg2+ in mitochondria has been demonstrated in yeast and it seems highly likely that the same will apply in plants. The chloroplasts also require significant amounts of internal Mg2+, and low concentrations of cytoplasmic Mg2+. In addition, it seems likely that the other subcellular organelles (e.g. Golgi, endoplasmic reticulum, etc) also require Mg2+.
The diagram shows a schematic of a plant and the putative processes of Mg2+ transport at the root and leaf where Mg2+ is loaded and unloaded from the vascular tissues. Mg2+ is taken up into the root cell wall space (1) and interacts with the negative charges associated with the cell walls and membranes. Mg2+ 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 Mg2+ 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 Mg2+ 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 Mg2+ reaches the leaves it is unloaded from the xylem into cells (6) and again is buffered in vacuoles (7). Whether cycling of Mg2+ into the phloem occurs via general cells in the leaf (8) or directly from xylem to phloem via transfer cells (9) is unknown. Mg2+ may return to the roots in the phloem sap.
When a Mg2+ 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. In vascular cells this is not always the case; in times of plenty Mg2+ 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 Mg2+ and many of the other ionic constituents, recycling them into healthy parts of the plant. Additionally, when Mg2+ in the environment is limiting some species are able to mobilise Mg2+ from older tissues. These processes involve the release of Mg2+ 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 Mg2+ is also remobilised within the plant as source and sink relationships change.
The homeostasis of Mg2+ 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. H+-ATPases pump H+ ions against their concentration gradient to maintain the pH differential that can be used for the transport of other ions and molecules. H+ ions are pumped out of the cytoplasm into the extracellular space or into the vacuole. The entry of Mg2+ into cells may occur through one of two pathways, via channels using the ΔΨ (negative inside) across this membrane or by symport with H+ ions. To transport the Mg2+ ion into the vacuole requires a Mg2+/H+ antiport transporter (such as AtMHX). It is interesting to note that the H+-ATPases are dependent on Mg2+ (bound to ATP) for activity, so that Mg2+ 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 Mg2+. H+-ATPases maintain a constant ΔpH across the plasma membrane and the vacuole membrane. Mg2+ is transported into the vacuole using the energy of ΔpH (in A. thaliana by AtMHX). Transport of Mg2+ into cells may use either the negative ΔΨ or the ΔpH. The transport of Mg2+ into mitochondria probably uses ΔΨ as in the mitochondria of yeast, and it is likely that chloroplasts take Mg2+ by a similar system. The mechanism and the molecular basis for the release of Mg2+ from vacuoles and from the cell is not known. Likewise the light-regulated Mg2+ concentration changes in chloroplasts are not fully understood, but do require the transport of H+ ions across the thylakoid membrane.
Mg2+ 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.
Whether Mg2+ 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 Mg2+ did move in and out of isolated chloroplasts from young pea plants, but Gupta and Berkowitz (1989) were unable to reproduce the result using older spinach chloroplasts. Deshaies et al. had stated in their paper that older pea chloroplasts showed less significant changes in Mg2+ 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+ is pumped out of the stroma (into both the cytoplasm and the lumen) leading to an alkaline pH. Mg2+ (along with K+) is released from the lumen into the stroma, in an electroneutralisation process to balance the flow of H+. Finally, thiol groups on enzymes are reduced by a change in the redox state of the stroma. Examples of enzymes activated in response to these changes are fructose 1,6-bisphosphatase, sedoheptulose bisphosphatase and ribulose-1,5-bisphosphate carboxylase. 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 Mg2+ in the stroma during the light phase can be identified. Firstly, enzymes in the glycolytic pathway most often interact with two atoms of Mg2+. 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 Mg2+ is complexed to nucleotide di- and tri-phosphates (ADP and ATP) and the chemical change involves phosphoryl transfer. Mg2+ may also serve in a structural maintenance role in these enzymes (e.g. enolase).
A Mg2+ deficit can be caused by the lack of the ion in the media (soil), but more commonly comes from inhibition of its uptake. Mg2+ binds quite weakly to the negatively charged groups in the root cell walls, so that excesses of other cations such as K+, NH4+, Ca2+ and Mn2+ can all impede uptake.(Kurvits and Kirkby, 1980; In acid soils Al3+ is a particularly strong inhibitor of Mg2+ uptake. The inhibition by Al3+ and Mn2+ is more severe than can be explained by simple displacement, hence it is possible that these ions bind to the Mg2+ uptake system directly. In bacteria and yeast, such binding by Mn2+ has already been observed. Stress responses in the plant develop as cellular processes halt due to a lack of Mg2+ (e.g. maintenance of ΔpH across the plasma and vacuole membranes). Interestingly, in Mg2+-starved plants under low light conditions the percentage of Mg2+ bound to chlorophyll has been recorded at 50%. Presumably, this imbalance has detrimental effects on other cellular processes.
Mg2+ toxicity stress is more difficult to develop. When Mg2+ 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 Mg2+ concentrations block a K+ channel in the inner envelope membrane of the chloroplast, in turn inhibiting the removal of H+ 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.
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