Biological Importance Of Magnasium

Magnesium is an essential element in biological systems. Magnesium occurs typically as the Mg2+ ion. It is an essential mineral nutrient for life[1][2] [3] and is present in every cell type in every organism. For example, 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. [4]. Similarly, magnesium plays a role in the stability of all polyphosphate compounds in the cells, including those associated with DNA and RNA

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 Mg2+ (and other ions) so transport proteins must facilitate the flow of Mg2+, both into and out of cells and intracellular compartments.

Biological range, distribution, and regulation •

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In animals it has been shown that different cell types maintain different concentrations of magnesium.[5][6][7][8] It seems likely that the same is true for plants.[9][10] 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[11]). 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.[12][13] The importance of magnesium to proper cellular function cannot be overstated. 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.[14][15] In yeast, mitochondrial magnesium deficiency is also leads to disease.[16] 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.[3] Magnesium can also be toxic to plants, although this is typically seen only in drought conditions. [17][18]

Biological range, distribution, and regulation •

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.[19] A number of genetically attributable hypomagnesemia disorders have also been identified in humans.[20][21][22][23] • 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

Human health •

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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 mg/day. Inadequate magnesium intake frequently causes muscle spasms, and has been associated with cardiovascular disease, diabetes, high blood pressure, anxiety disorders, migraines, osteoporosis and cerebral infarction[24]. 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 DRI upper tolerated limit for supplemental magnesium is 350 mg/day (calculated as milligrams (mg) of elemental magnesium in the salt). (Supplements based on amino acid chelates, such as glycinate, lysinate etc., are much better tolerated by the digestive system and do not have the side effects of the older compounds used, while sustained release supplements prevent the occurrence of diarrhea.)[citation needed] 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

Human health 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

Nerve Conduction • Magnesium can effect muscle relaxation through direct action on the cell membrane. Mg++ ions close certain types of calcium channels, which conduct a positively charged calcium ion into the neuron. With an excess of magnesium, more channels will be blocked and the nerve will have less activity

Hypertension • Magnesium-containing Epsom salts are especially used in treating 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[26], so with magnesium chloride, the increase in osmolarity may not cause such a hypertensive response

Food sources • • • •

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Some good sources of magnesium. 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: 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

Biological chemistry • Mg2+ 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, Mg2+-dependent enzymes appear in virtually every metabolic pathway: specific binding of Mg2+ to biological membranes is frequently observed, Mg2+ is also used as a signalling molecule, and much of nucleic acid biochemistry requires Mg2+, including all reactions which require release of energy from ATP.[27] [28][13] In nucleotides, the triple phosphate moiety of the compound is invariably stabilized by association with Mg2+ in all enzymic processes.

Chlorophyll • 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

Enzymes •

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.[27][29][30][31] 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

Essential role in the biological activity of ATP • 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

Nucleic acids •

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 doublestranded DNA in the presence of Mg2+.[27] Additionally, ribosomes contain large amounts of Mg2+ and the stabilisation provided is essential to the complexation of this ribo-protein.[33] 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[34]). • 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

Cell membranes and walls •

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.[27] 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.[12]

Proteins •

The Mg2+ ion tends to bind only weakly to proteins (Ka ≤ 105[27]) 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[36] 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

Importance in drug binding • An article[37] 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 Mg2+ ions for the binding of some drugs

Plant physiology of magnesium • The previous sections have dealt in detail with the chemical and biochemical aspects of Mg2+ 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 •

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Mg2+ is essential for plant growth and is present in higher plants in amounts on the order of 80 μmol g-1 dry weight.[3] The amounts of Mg2+ vary in different parts of the plant and are dependent upon nutritional status. In times of plenty, excess Mg2+ may be stored in vascular cells (Stelzer et al., 1990;[10] and in times of starvation Mg2+ is redistributed, in many plants, from older to newer leaves.[3][51] 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;[52] 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.[53] 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.[54] The requirement for Mg2+ in mitochondria has been demonstrated in yeast[55] 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+.[56][57] In addition, it seems likely that the other subcellular organelles (e.g. Golgi, endoplasmic reticulum, etc) also require Mg2

Magnesium, chloroplasts and photosynthesis •

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Mg2+ is the coordinating metal ion in the chlorophyll molecule, and in plants where the ion is in high supply about 6% of the total Mg2+ is bound to chlorophyll.[3][61][62] Thylakoid stacking is stabilised by Mg2+ and is important for the efficiency of photosynthesis, allowing phase transitions to occur.[63] 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.[64] [65] 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,[66] but Gupta and Berkowitz (1989) were unable to reproduce the result using older spinach chloroplasts.[67] 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.

Magnesium, chloroplasts and photosynthesis •

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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.[68][69] Mg2+ (along with K+) is released from the lumen into the stroma, in an electroneutralisation process to balance the flow of H+.[70][71][72][73] Finally, thiol groups on enzymes are reduced by a change in the redox state of the stroma. [74] Examples of enzymes activated in response to these changes are fructose 1,6bisphosphatase, sedoheptulose bisphosphatase and ribulose-1,5-bisphosphate carboxylase.[3][30][74] 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.[30] 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).

Magnesium is also used: • • • • • • • • • •

To remove sulfur from iron and steel. To refine titanium in the Kroll process. To photoengrave plates in the printing industry. To combine in alloys, where this metal is essential for airplane and missile construction. In the form of turnings or ribbons, to prepare Grignard reagents, which are useful in organic synthesis. As an alloying agent, improving the mechanical, fabrication and welding characteristics of aluminium. As an additive agent in conventional propellants and the production of nodular graphite in cast iron. As a reducing agent for the production of uranium and other metals from their salts. As a desiccant, since it easily reacts with water. As a sacrificial (galvanic) anode to protect underground tanks, pipelines, buried structures, and water heaters.

magnesium compounds • •

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The magnesium ion is necessary for all life (see magnesium in biology), so magnesium salts are an additive for foods, fertilizers (Mg is a component of chlorophyll), and culture media. Magnesium hydroxide is used in milk of magnesia, its chloride, oxide, gluconate, malate, orotate and citrate used as oral magnesium supplements, and its sulfate (Epsom salts) for various purposes in medicine, and elsewhere (see the article for more). Oral magnesium supplements have been claimed to be therapeutic for some individuals who suffer from Restless Leg Syndrome (RLS).[citation needed] Magnesium borate, magnesium salicylate and magnesium sulfate are used as antiseptics. Magnesium bromide is used as a mild sedative (this action is due to the bromide, not the magnesium). Dead-burned magnesite is used for refractory purposes such as brick and liners in furnaces and converters. Magnesium carbonate (MgCO3) powder is also used by athletes, such as gymnasts and weightlifters, to improve the grip on objects – the apparatus or lifting bar

magnesium compounds • Magnesium stearate is a slightly flammable white powder with lubricative properties. In pharmaceutical technology it is used in the manufacturing of tablets, to prevent the tablets from sticking to the equipment during the tablet compression process (i.e., when the tablet's substance is pressed into tablet form). • Magnesium sulfite is used in the manufacture of paper ( sulfite process). • Magnesium phosphate is used to fireproof wood for construction. • Magnesium hexafluorosilicate is used in mothproofing of textiles

Biological role •

Due to the important interaction between phosphate and magnesium ions, magnesium ions are essential to the basic nucleic acid chemistry of life, and thus are essential to all cells of all known living organisms. Over 300 enzymes require the presence of magnesium ions for their catalytic action, including all enzymes utilizing or synthesizing ATP, or those which use other nucleotides to synthesize DNA and RNA. ATP exists in cells normally as a chelate of ATP and a magnesium ion. • Plants have an additional use for magnesium in that chlorophylls are magnesium-centered porphyrins. Magnesium deficiency in plants causes late-season yellowing between leaf veins, especially in older leaves, and can be corrected by applying Epsom salts (which is rapidly leached), or else crushed dolomitic limestone to the soil.

Food sources of magnesium •

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(Magnesium is a vital component of a healthy human diet. Human magnesium deficiency including conditions which show few overt symptoms) is relatively common, with only 32% of the United States meeting the RDA-DRI,[9] and has been implicated in the development of a number of human illnesses such as asthma, osteoporosis, and ADHD.[10] Adult human bodies contain about 24 grams of magnesium, with 60% in the skeleton, 39% intracellular (20% in skeletal muscle), and 1% extracellular. Serum levels are typically 0.7 – 1.0 mmol/L. Serum magnesium levels may appear normal even in cases of underlying intracellular deficiency, although no known mechanism maintains a homeostatic level in the blood other than renal excretion of high blood levels. Intracellular magnesium is correlated with intracellular potassium. Magnesium is absorbed in the gastrointestinal tract, with more absorbed when status is lower. In humans, magnesium appears to facilitate calcium absorption. Low and high protein intake inhibit magnesium absorption, and other factors such as phosphate, phytate, and fat affect absorption. Absorbed dietary magnesium is largely excreted through the urine, although most magnesium "administered orally" is excreted through the feces.[11] Magnesium status may be assessed roughly through serum and erythrocyte Mg concentrations and urinary and fecal excretion, but intravenous magnesium loading tests are likely the most accurate and practical in most people. [12] In these tests, magnesium is injected intravenously; a retention of 20% or more indicates deficiency.[13] Other nutrient deficiencies are identified through biomarkers, but none are established for magnesium.[14]

Food sources of magnesium • Spices, nuts, cereals, coffee, cocoa, tea, and vegetables (especially green leafy ones) are rich sources of magnesium. Observations of reduced dietary magnesium intake in modern Western countries as compared to earlier generations may be related to food refining and modern fertilizers which contain no magnesium