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The Magnesium Project - Muscle Diseases
There are a number of studies that have shown that Mg is an important factor in a number of diseases of muscles. It is not surprising that this is so since one of the factors in maintaining normal electrical signals along nerve fibers is the active Na-K-Mg-activated ATPase enzyme that catalyzes the movement of Na out of cells and K into cells to maintain a voltage difference of approximately -90 millivolts. Without this voltage potential difference, and ionic distribution, there would not be a normal action potential to transmit down a nerve or muscle fiber. In addition to maintain electrical and physical-chemical gradients, Mg is involved in many other energy-requiring chemical and motor activities of the nerve cell. The interaction of the proteins Actin and Myosin is dependent upon both calcium and Mg. The release of Ca from a bound membrane state and its active re-uptake plays a key role in muscle energetics. In recent years there has been considerable study on different types of Ca channel and the modes of transport across muscle membranes. It is known that Mg in its hydrated state can interfere with this transport. Both the Na/K pump and the Ca-Myosin binding are driven by the breakdown of ATP into ADP. Mg is involved in most biochemical reactions involving phosphorylation - either losing it from ATP or putting it back on to ADP. In addition, the metabolic pathways that generate high energy ATP are dependent in many steps upon Mg-activated enzymes. Kinases are one large family of enzymes that are for the most part dependent upon Mg for activation. Nitric Oxide (NO) regulatory pathways The NO synthesis pathway, involves both enzymatic and non-enzymatic pathways. L-arginine is converted to NO and citrulline in the presence of NADPH and oxygen. The NOS pathways depends on essential cofactors (BH4, FAD, FMN and heme) for their activity; NOS1 and NO3 are also Ca2+ dependent. De novo arginine production from citrulline involves the enzymes ASS and ASL. [Regulation of Nitric Oxide Production in Health and Disease. Curr Opin Clin Nutr Metab Care;13(1):97-104. http://www.ncbi.nlm.nih.gov/pubmed/19841582]. Given the Ca++ dependence of one step, there is the potential for a Mg++ antagonism of this step among others in the metabolic chain for nitric oxide synthesis. Whether this is involved in the effect of Mg++ on smooth muscle relaxation is speculation at this point. Other Influences
Specific indicators to be alert for when dealing with these diseases are the blood electrolyte levels. If the Magnesium level is higher or lower than normal, that condition would be designated as either Hypermagnesemia or Hypomagnesemia respectively. It may also be important to look for abnormal levels of Ca, Na, and K. Often the physiological effects are not only level sensitive but also ratio sensitive. Thus a low Mg may not be as much of a problem for some diseases if the Ca were also low. Similarly, Mg/K and Ca/K and Na/K ratios are often good indicators of impending malfunction as much as the absolute levels, though the later are certainly important. See the section on Hypomagnesemia for further discussion. Genetic conditions that may be pre-disposing to any of the foregoing conditions are yet to be evaluated. For further treatment of genetics see the Genomics pages. References Erion Qamirani, Allyson G. Nelson, Daniel R. Hyduke, Gautam Haudhuri et al. Regulation of nitric oxide consumption by hypoxic red blood cells PNAS October 14, 2003 vol. 100 no. 21 12504-12509 [http://www.pnas.org/content/100/21/12504.full ] [More available] -------------------------------------- ---------------------------------------
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