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Magnesium - "The Missing Mineral"

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Magnesium Maintains Cell Membrane"Battery"

Magnesium powers cell “Battery”

First some background on the cell battery and its transmembrane pumps

What is the cell "Battery"?

The cell "battery" is the voltage difference across the plasma cell membrane (a.k.a. the transmembrane potential).    Typically -70 mV in a healthy cell, with outer membrane being more positive than inside. The charge difference is determined by an imbalance of mineral ions, such as K+, Na+, Ca++ and H+, separated on either side of the membrane.

The Cell Battery

Body's energy currency ATP and the protein enzyme ATPase

ATP (adenosine triphosphate) is produced by ALL of our cells (by cell mitochondria) to store energy (as phosphate bonds) to be used for work in the cell - in an aqueous medium, energy is released from ATP by the enzyme ATPase, which breaks down  (hydrolizes) the phosphate bonds in ATP (into ADP plus a free phosphate ion). Without the ATPase enzyme, ATP's stored energy can not be extracted.

Some ATPases are transmembrane pumps

Transmembrane pumps are ATPases that provide an active transport channel for ions, such as H+, Na+, K+ , Ca2+ across a cell membrane - transmembrane ATPases (pumps) are integral proteins of the membrane which make it possible for the solute ions /molecules to diffuse across the membrane against their concentration gradient (i.e. Via active transport) using energy released by the hydrolysis/ break down of ATP.

The most significant pumps are:

•    Sodium/Potassium pump (Na+/K+- ATPase) - found in the plasma membrane of all animal cells; used to maintain the transmembrane potential (voltage) by powering movement of sodium ions (out of the cell) and potassium ions (into the cell) across the membrane against their gradient

•    Bicarbonate pump (HCO3 -ATPase) - present in parietal cell membranes in stomach;  used to acidfy the stomach

•    Calcium pump (Ca2+-ATPase) -

Magnesium is necessary to power the transmembrane transport pumps

Sodium / potassium pump

ATP must be bound to a magnesium ion to be biologically active.   Investigations of the Na/K-ATPase established that Mg2+ is an essential cofactor for activation of enzymatic ATP hydrolysis to release cellular energy from ATP.

 ATP + Mg2+ <--> MgATP2-.

MgATP2-. binds to the ATPase enzyme (on the cytoplasmic side of the membrane, without magnesium being transported through the cell membrane) and remains bound throughout the reaction cycle at least until after the release of phosphate.   Most ATPase enzymes break down MgATP2-.

Magnesium also REGULATES ATP production - experimental evidence collected through the years confirms that Mg2+ ions have a regulatory effect on ion transport by interacting with the cytoplasmic side of the ion pump.

Apell HJ et al, Modulation of the Na,K-ATPase by Magnesium Ions. Biochemistry, 2017 Feb 21;56(7):1005-1016.

Fukushima & Post, Binding of divalent cation to phosphoenzyme of sodium- and potassium-transport adenosine triphosphatase, 1978 JBC

MILDVAN, A. S. (1987). Role of magnesium and other divalent cations in ATP-utilizing enzymes. Magnesium 6, 28-33.

Effects of having insufficient magnesium available for transmembrane pumps

Lack of magnesium allows cells to swell

Gradient created by Na/K pump is used to expel excess water from cell to prevent it from swelling;

Lack of magnesium reduces cell "battery" voltage

The Magnesium-dependent Na/K pumps maintain appropriate intracellular/extracellular potassium/sodium ion concentrations

-   The Na/K pumps are opened or closed when stimulated by a change in the cell “battery” voltage - the opening of the Na/K pump generates an inward current that affects the membrane potential itself (creating a reinforcing positive loop).

-   "No gas (i.e. magnesium), No Go !"- a malfunctioning Na/K pump due to a lack of Mg-dependent ATP reduces the cell “battery” voltage and mitochondrial ATP energy production in the cell, which further negatively affects Na/K pumps. A rat study found that a magnesium deficiency decreased Na/K pump activity in heart cell membranes. Effects of dietary magnesium on sodium-potassium pump action in the heart of rats.

Chronic magnesium deficiency  leads to intracellular calcification

Magnesium is a natural calcium channel blocker, responsible for muscle relaxation to counter calcium's contraction

Na gradient generated by Magnesium-dependent Na/K pumps is used by cell membrane and endoplasmic reticulum membrane calcium pumps (Na+ - Ca2+ translocators, found in smooth and striated muscle cells) to regulate calcium concentration in the cell's cytoplasm (i.e. inside the cell).    Calcium usually enters cells for an excitory action E.g. a muscle contraction or nerve impulse. Once its job is done, magnesium empowers calcium pumps to flush calcium out of the cell against its gradient, or into intracellular calcium stores, such as the sarcoplasmic reticulum of muscle cells or mitochondria of all cells). A deficiency of magnesium leads to calcium accumulation inside cells (called calcification) , which can result in over excitation in nerve and muscle cells. This not only affects "movement muscle" contractions (seen as spasms), but also affects heart and arterial contractions.

Familiar health consequences ensue as calcium accumulates inside cells (calcification).   Includingarteriosclerosis/CVD, cancer, hypertension, arrhythmias, angina pectoris, neurodegenerative diseases, muscle/joint pain and stiffness, muscle spasms/ twitching, tension / migraine headaches, painful menstrual ramping, cataracts, bone spurs, and on and on . . .

Effects of calcification include:

•   Build up of calcium in soft tissues

Magnesium prevents soft tissue calcification

•    Inability to relax muscles.   Muscle contraction depends on a calcium ion concentration bout 10,000 times higher than its resting concentration inside cells, which is accomplished by pumping calcium in via the membrane calcium pumps and by using calcium pumps in the sarcoplasmic reticulum (SR) (a storage depot for calcium, which is a special type of endoplasmic reticulum found in smooth and striated muscle that sequesters then releases calcium when the muscle is stimulated to contract). Muscle relaxation occurs when calcium is quickly returned from whence it came, which may not occur effectively with a magnesium deficiency.

Magnesium - Muscles Relaxant

•   Protein/Lipid synthesis and carbohydrate/steroid metabolism.   In its role in powering the endoplasmic reticulum membrane calcium pumps, Mg serves to regulate calcium concentrations in the cytoplasm by stimulating sequestration of calcium into the cell's endoplasmic reticula, which are responsible for:

•  Synthesis of proteins / triglycerides / phospholipids / steroids;

•  Metabolism of carbohydrates / steroids;

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