Magnesium metabolism

Jang Won Seo, Tae Jin Park, Jang Won Seo, Tae Jin Park

Abstract

Magnesium is the second most common intracellular divalent cation. Magnesium balance in the body is controlled by a dynamic interplay among intestinal absorption, exchange with bone, and renal excretion. Intestinal magnesium absorption proceeds in both a passive paracellular and an active transcellular manner. Regulation of serum magnesium concentrations is achieved mainly by control of renal magnesium reabsorption. Only 20% of filtered magnesium is reabsorbed in the proximal tubule, whereas 60% is reclaimed in the cortical thick ascending limb (TAL) and another 5-10% in the distal convoluted tubule (DCT). The passive paracellular transport of magnesium in the TAL is closely related with the mutations in claudin-16/paracellin-1 and is responsible for familial hypomagnesemia with hypercalciuria and nephrocalcinosis. The active transcellular transport of magnesium in the DCT was similarly enhanced by the realization that defects in transient receptor potential melastatin 6 (TRPM6) cause hypomagnesemia with secondary hypocalcemia. This channel regulates the apical entry of magnesium into epithelia and alters whole-body magnesium homeostasis by controlling urinary excretion. TRPM6 is regulated at the transcriptional level by acid-base status, 17β-estradiol, and both FK506 and cyclosporine. The molecular identity of the protein responsible for the basolateral exit of magnesium from the epithelial cell remains unidentified.

Keywords: homeostasis; magnesium; paracellular transport; transcellular transport; transient receptor potential channels.

Figures

Fig. 1
Fig. 1
Distribution of chemical forms of magnesium in serum. Of total body magnesium, 67% is found in bone and hard tissue; 31% is found inside cells; and approximately 2% is found in serum.
Fig. 2
Fig. 2
Distribution of magnesium in the body.
Fig. 3
Fig. 3
Renal regulation of magnesium homeostasis. Model of thick ascending limb (TAL) and distal convoluted tubule (DCT), showing predominant magnesium transport pathways. CLCKb, voltage-dependent chloride channel; claudin-16, paracellin; NKA, Na+,K+-ATPase; NKCC2, Na+/K+/2Cl- cotransporter; ROMK, inwardly rectifying potassium channel; TSC, thiazide-sensitive Na+/Cl- cotransporter.

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